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Sample records for lupus-associated autoantigen smd

  1. Immunogenicity of autoantigens

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2011-07-01

    Full Text Available Abstract Background Autoantibodies against self-antigens have been associated not only with autoimmune diseases, but also with cancer and are even found in healthy individuals. The mechanism causing the autoantibody response remains elusive for the majority of the immunogenic antigens. To deepen the understanding of autoantibody responses, we ask whether natural-occurring, autoimmunity-associated and tumor-associated antigens have structural or biological features related to the immune response. To this end, we have carried out the most comprehensive in-silicio study of different groups of autoantigens including large antigen sets identified by our groups combined with publicly available antigen sets. Results We found evidence for an enrichment of genes with a larger exon length increasing the probability of the occurrence of potential immunogenic features such as mutations, SNPs, immunogenic sequence patterns and structural epitopes, or alternative splicing events. While SNPs seem to play a more central role in autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated antigens. In addition, antigens of autoimmune diseases are different from other antigen sets in that they appear preferentially secreted, have frequently an extracellular location, and they are enriched in pathways associated with the immune system. Furthermore, for autoantibodies in general, we found enrichment of sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to proteins or nucleic acids including RNA and enrichment of proteins that are part of ribosome or spliceosome. Both, homologies to proteins of other species and an enrichment of ancient protein domains indicate that immunogenic proteins are evolutionary conserved and that mimicry might play a central role. Conclusions Our results provide evidence that proteins which i are evolutionary conserved

  2. [Biological disturbances during the lupus-associated pancreatitis: case report].

    Science.gov (United States)

    Sayagh, Sanae; Benchekroun, Leila; Bouabdellah, Mounya; Jaouhar, Nezha; El Aoufi, Farida; El Oufir, Fatiha; Alaoui, Meryem; Adnaoui, Mohammed; Chabraoui, Layachi

    2015-01-01

    We report in this paper the case of female patient, hypertriglyceridemia associated with milky serum and hyperglycemia have been the alarm signal of a lupus-associated pancreatitis, the confirmation of this entity was done with elevated rate of serum lipase activity. It is about a 33 years age female. She has as unique antecedent a lupus diagnosed on January of the same. The patient was admitted on august 2013 for another episode of lupus associated to the lower lamb edema with a rate of C3 at 0.4 g/L (0.82-1,93) and C4 at 0.05 g/L (0.15-0.57). One day after the beginning of the corticotherapy, the patient presented hyperthermia, ataxis and behavior troubles, epigastric and articular pains and vomiting. Biochemical tests found hyperglycemia at 38.9 mmol/L (3.9-6.1), dyslipidemia with hypertriglyceridemia at 15.7 mmol/L (0.3-1.7) and total cholesterol rate at 5.2 mmol/L (<5.2) associated with milky serum. Haematological tests objective normocytic normochromic anemia with 81 g/L of hemoglobin, lymphopenia at 0.88 G/L and normal platelet rate. Lupus associated pancreatitis was suggested and confirmed biologically with an hyperlipasemia at 180 UI/L (8-78) and radiologicaly with the image of focal hepatic steatosis. We conclude that on the presence of lupus, gastrointestinal and/or biological signs must motivate the measurement of the serum lipase activity as quickly as possible to assess the diagnosis of lupus-associated pancreatitis.

  3. Radiometallating antibodies and autoantigenic peptides

    International Nuclear Information System (INIS)

    Mercer-Smith, J.A.; Lewis, D.; Cole, D.A.; Newmyer, S.L.; Schulte, L.D.; Mixon, P.L.; Schreyer, S.A.; Burns, T.P.; Roberts, J.C.; Figard, S.D.; McCormick, D.J.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

    1991-01-01

    We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N- benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have one functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies and have developed methods to label smaller biologically active molecules, such as autoantigenic peptides (fragments of the acetylcholine receptor), which are pertinent to myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules, the radiometallation chemistry, and biological characterization of the radiolabeled compounds will be discussed

  4. SMD-based numerical stochastic perturbation theory

    Energy Technology Data Exchange (ETDEWEB)

    Dalla Brida, Mattia [Universita di Milano-Bicocca, Dipartimento di Fisica, Milan (Italy); INFN, Sezione di Milano-Bicocca (Italy); Luescher, Martin [CERN, Theoretical Physics Department, Geneva (Switzerland); AEC, Institute for Theoretical Physics, University of Bern (Switzerland)

    2017-05-15

    The viability of a variant of numerical stochastic perturbation theory, where the Langevin equation is replaced by the SMD algorithm, is examined. In particular, the convergence of the process to a unique stationary state is rigorously established and the use of higher-order symplectic integration schemes is shown to be highly profitable in this context. For illustration, the gradient-flow coupling in finite volume with Schroedinger functional boundary conditions is computed to two-loop (i.e. NNL) order in the SU(3) gauge theory. The scaling behaviour of the algorithm turns out to be rather favourable in this case, which allows the computations to be driven close to the continuum limit. (orig.)

  5. SMD-based numerical stochastic perturbation theory

    International Nuclear Information System (INIS)

    Dalla Brida, Mattia; Luescher, Martin

    2017-01-01

    The viability of a variant of numerical stochastic perturbation theory, where the Langevin equation is replaced by the SMD algorithm, is examined. In particular, the convergence of the process to a unique stationary state is rigorously established and the use of higher-order symplectic integration schemes is shown to be highly profitable in this context. For illustration, the gradient-flow coupling in finite volume with Schroedinger functional boundary conditions is computed to two-loop (i.e. NNL) order in the SU(3) gauge theory. The scaling behaviour of the algorithm turns out to be rather favourable in this case, which allows the computations to be driven close to the continuum limit. (orig.)

  6. SMD-based numerical stochastic perturbation theory

    Science.gov (United States)

    Dalla Brida, Mattia; Lüscher, Martin

    2017-05-01

    The viability of a variant of numerical stochastic perturbation theory, where the Langevin equation is replaced by the SMD algorithm, is examined. In particular, the convergence of the process to a unique stationary state is rigorously established and the use of higher-order symplectic integration schemes is shown to be highly profitable in this context. For illustration, the gradient-flow coupling in finite volume with Schrödinger functional boundary conditions is computed to two-loop (i.e. NNL) order in the SU(3) gauge theory. The scaling behaviour of the algorithm turns out to be rather favourable in this case, which allows the computations to be driven close to the continuum limit.

  7. Autoantibodies from patients with systemic lupus erythematosus bind a shared sequence of SmD and Epstein-Barr virus-encoded nuclear antigen EBNA I.

    Science.gov (United States)

    Sabbatini, A; Bombardieri, S; Migliorini, P

    1993-05-01

    SmD is one of the small nuclear ribonucleoproteins frequently targeted by autoantibodies in systemic lupus erythematosus. We isolated and characterized the antibodies present in lupus sera that are specific for the C-terminal region of SmD (sequence 95-119). This region is highly homologous to sequence 35-58 of the EBNA I antigen, one of the nuclear antigens induced by infection with Epstein-Barr virus. Antibodies affinity purified over a peptide 95-119 column were able to recognize this sequence in the context of the whole SmD molecule, as they reacted with blotted recombinant SmD. Anti-SmD 95-119 antibodies bound also the EBNA I 35-58 peptide and detected the EBNA I molecule in a total cell extract from Epstein-Barr virus-infected lines. A population of anti-SmD antibodies is, therefore, able to bind an epitope shared by the autoantigen and the viral antigen EBNA I. To investigate the involvement of this shared epitope in the generation of anti-SmD antibodies, we immunized mice with the EBNA I 35-58 peptide. Sera from immunized animals displayed the same pattern of reactivity of spontaneously produced anti-SmD antibodies. They reacted in fact with the EBNA peptide as well as with SmD 95-119 and recombinant SmD. These data suggest that molecular mimicry may play a role in the induction of anti-SmD autoantibodies.

  8. SMD Technology Development Story for NASA Annual Technology report

    Science.gov (United States)

    Seablom, Michael S.

    2017-01-01

    The role of the Science Mission Directorate (SMD) is to enable NASA to achieve its science goals in the context of the Nation's science agenda. SMD's strategic decisions regarding future missions and scientific pursuits are guided by Agency goals, input from the science community-including the recommendations set forth in the National Research Council (NRC) decadal surveys-and a commitment to preserve a balanced program across the major science disciplines. Toward this end, each of the four SMD science divisions-Heliophysics, Earth Science, Planetary Science, and Astrophysics-develops fundamental science questions upon which to base future research and mission programs. Often the breakthrough science required to answer these questions requires significant technological innovation-e.g., instruments or platforms with capabilities beyond the current state of the art. SMD's targeted technology investments fill technology gaps, enabling NASA to build the challenging and complex missions that accomplish groundbreaking science.

  9. Biomechanically Excited SMD Model of a Walking Pedestrian

    DEFF Research Database (Denmark)

    Zhang, Mengshi; Georgakis, Christos T.; Chen, Jun

    2016-01-01

    Through their biomechanical properties, pedestrians interact with the structures they occupy. Although this interaction has been recognized by researchers, pedestrians' biomechanical properties have not been fully addressed. In this paper, a spring-mass-damper (SMD) system, with a pair of biomech......Through their biomechanical properties, pedestrians interact with the structures they occupy. Although this interaction has been recognized by researchers, pedestrians' biomechanical properties have not been fully addressed. In this paper, a spring-mass-damper (SMD) system, with a pair...... produced the pedestrian's center of mass (COM) trajectories from the captured motion markers. The vertical COM trajectory was approximated to be the pedestrian SMD dynamic responses under the excitation of biomechanical forces. SMD model parameters of a pedestrian for a specific walking frequency were...... estimated from a known walking frequency and the pedestrian's weight, assuming that pedestrians always walk in displacement resonance and retain a constant damping ratio of 0.3. Thus, biomechanical forces were extracted using the measured SMD dynamic responses and the estimated SMD parameters. Extracted...

  10. An Aggregated Optimization Model for Multi-Head SMD Placements

    NARCIS (Netherlands)

    Ashayeri, J.; Ma, N.; Sotirov, R.

    2010-01-01

    In this article we propose an aggregate optimization approach by formulating the multi-head SMD placement optimization problem into a mixed integer program (MIP) with the variables based on batches of components. This MIP is tractable and effective in balancing workload among placement heads,

  11. An aggregated optimization model for multi-head SMD placements

    NARCIS (Netherlands)

    Ashayeri, J.; Ma, N.; Sotirov, R.

    2011-01-01

    In this article we propose an aggregate optimization approach by formulating the multi-head SMD placement optimization problem into a mixed integer program (MIP) with the variables based on batches of components. This MIP is tractable and effective in balancing workload among placement heads,

  12. Epigenetics of Autoantigens: New Opportunities for Therapy of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Marko Radic

    2013-01-01

    Full Text Available The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity.

  13. Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

    Science.gov (United States)

    Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

    2016-01-01

    Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Identification of new celiac disease autoantigens using proteomic analysis

    Czech Academy of Sciences Publication Activity Database

    Stulík, J.; Hernychová, L.; Porkertová, S.; Pozler, O.; Tučková, Ludmila; Sánchez, Daniel; Bureš, J.

    2003-01-01

    Roč. 3, - (2003), s. 951-956 ISSN 1615-9853 R&D Projects: GA ČR GA310/00/1373; GA AV ČR IBS5020203 Institutional research plan: CEZ:AV0Z5020903 Keywords : autoantigens * cells disease Subject RIV: EE - Microbiology, Virology Impact factor: 5.766, year: 2003

  15. Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wesley H. Brooks

    2013-04-01

    Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.

  16. Low-cost millimeter-wave transceiver module using SMD packaged MMICs

    NARCIS (Netherlands)

    Heijningen, M. van; Gauthier, G.

    2004-01-01

    This paper presents a novel approach to realize low-cost millimeter-wave modules using only SMD packaged MMICs integrated on a single organic substrate. This approach is demonstrated on a 38 GHz transceiver module for point-to-point LMDS communication systems. The required SMD package technology and

  17. Low-Cost Millimeter-Wave Transceiver Module using SMD packaged MMICs.

    NARCIS (Netherlands)

    2004-01-01

    This paper presents a novel approach to realize low-cost millimeter-wave modules using only SMD packaged MMICs integrated on a single organic substrate. This approach is demonstrated on a 38 GHz transceiver module for point-to-point LMDS communication systems. The required SMD package technology and

  18. Osteopontin is a tumor autoantigen in prostate cancer patients

    Science.gov (United States)

    TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

    2011-01-01

    Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

  19. Identification of human cytochrome P450s as autoantigens.

    Science.gov (United States)

    Manns, M P; Johnson, E F

    1991-01-01

    Antimicrosomal antibodies in inflammatory liver diseases all seem to be directed against members of the cytochrome P450 family of proteins. These autoantigens seem to be genetically polymorphic, the autoantibodies are inhibitory, and the autoepitopes are generally conserved among species. Anti-P450 autoantibodies share these characteristics with other autoantibodies, for example, antinuclear antibodies in systemic lupus erythematosus. The identification of P450s as human autoantigens is clinically important. Diagnostic tests will be developed on the basis of cloned antigen, facilitating a better diagnosis of drug-induced and idiopathic autoimmune hepatitis. It is unknown what triggers autoantibody production against cytochrome P450 proteins. Furthermore, their pathogenetic role and thus their involvement in tissue destruction is unclear. In this context LKM1 autoantibodies may serve as a model. Although LKM1 antibodies are inhibitory, all LKM1 antibody-positive patients tested so far are extensive metabolizers for drug metabolism mediated by P450IID6 and express this protein in their livers. Thus, the inhibitory LKM1 autoantibody does not sufficiently penetrate through the intact liver cell membrane to inhibit enzyme function in vivo. Presumably, tissue destruction in autoimmune hepatitis is mediated by liver-infiltrating T lymphocytes. T lymphocytes have been cloned from liver tissue that specifically proliferate in the presence of recombinant cytochrome P450IID6. The construction of overlapping cDNA subclones is also valuable to identify immunodominant B cell as well as relevant T cell epitopes.

  20. NASA SMD Science Education and Public Outreach Forums: A Five-Year Retrospective

    Science.gov (United States)

    Smith, Denise A.; Peticolas, Laura; Schwerin, Theresa; Shipp, Stephanie

    2014-06-01

    NASA’s Science Mission Directorate (SMD) created four competitively awarded Science Education and Public Outreach Forums (Astrophysics, Heliophysics, Planetary Science, Earth Science) in 2009. The objective is to enhance the overall coherence of SMD education and public outreach (E/PO), leading to more effective, efficient, and sustainable use of SMD science discoveries and learning experiences. We summarize progress and next steps towards achieving this goal with examples drawn from Astrophysics and cross-Forum efforts. Over the past five years, the Forums have enabled leaders of individual SMD mission and grant-funded E/PO programs to work together to place individual science discoveries and learning resources into context for audiences, conveying the big picture of scientific discovery based on audience needs. Forum-organized collaborations and partnerships extend the impact of individual programs to new audiences and provide resources and opportunities for educators to engage their audiences in NASA science. Similarly, Forum resources support scientists and faculty in utilizing SMD E/PO resources. Through Forum activities, mission E/PO teams and grantees have worked together to define common goals and provide unified professional development for educators (NASA’s Multiwavelength Universe); build partnerships with libraries to engage underserved/underrepresented audiences (NASA Science4Girls and Their Families); strengthen use of best practices; provide thematic, audience-based entry points to SMD learning experiences; support scientists in participating in E/PO; and, convey the impact of the SMD E/PO program. The Forums have created a single online digital library (NASA Wavelength, http://nasawavelength.org) that hosts all peer-reviewed SMD-funded education materials and worked with the SMD E/PO community to compile E/PO program metrics (http://nasamissionepometrics.org/). External evaluation shows the Forums are meeting their objectives. Specific examples

  1. Automated microfluidic assay system for autoantibodies found in autoimmune diseases using a photoimmobilized autoantigen microarray.

    Science.gov (United States)

    Matsudaira, Takahiro; Tsuzuki, Saki; Wada, Akira; Suwa, Akira; Kohsaka, Hitoshi; Tomida, Maiko; Ito, Yoshihiro

    2008-01-01

    Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and autoimmune diabetes are characterized by the production of autoantibodies that serve as useful diagnostic markers, surrogate markers, and prognostic factors. We devised an in vitro system to detect these clinically pivotal autoantibodies using a photoimmobilized autoantigen microarray. Photoimmobilization was useful for preparing the autoantigen microarray, where autoantigens are covalently immobilized on a plate, because it does not require specific functional groups of the autoantigens and any organic material can be immobilized by a radical reaction induced by photoirradiation. Here, we prepared the microarray using a very convenient method. Aqueous solutions of each autoantigen were mixed with a polymer of poly(ethylene glycol) methacrylate and a photoreactive crosslinker, and the mixtures were microspotted on a plate and dried in air. Finally, the plate was irradiated with an ultraviolet lamp to obtain immobilization. In the assay, patient serum was added to the microarray plate. Antigen-specific IgG adsorbed on the microspotted autoantigen was detected by peroxidase-conjugated anti-IgG antibody. The chemical luminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All autoantigens were immobilized stably by this method and used to screen antigen-specific IgG. In addition, the plate was covered with a polydimethylsiloxane sheet containing microchannels and automated measurement was carried out.

  2. Discovery of native autoantigens via antigen surrogate technology: application to type 1 diabetes.

    Science.gov (United States)

    Doran, Todd M; Simanski, Scott; Kodadek, Thomas

    2015-02-20

    A fundamental goal in understanding the mechanisms of autoimmune disease is the characterization of autoantigens that are targeted by autoreactive antibodies and T cells. Unfortunately, the identification of autoantigens is a difficult problem. We have begun to explore a novel route to the discovery of autoantibody/autoantigen pairs that involves comparative screening of combinatorial libraries of unnatural, synthetic molecules for compounds that bind antibodies present at much higher levels in the serum of individuals with a given autoimmune disease than in the serum of control individuals. We have shown that this approach can yield "antigen surrogates" capable of capturing disease-specific autoantibodies from serum. In this report, we demonstrate that the synthetic antigen surrogates can be used to affinity purify the autoantibodies from serum and that these antibodies can then be used to identify their cognate autoantigen in an appropriate tissue lysate. Specifically, we report the discovery of a peptoid able to bind autoantibodies present in about one-third of nonobese diabetic (NOD) mice. The peptoid-binding autoantibodies were highly enriched through peptoid affinity chromatography and employed to probe mouse pancreatic and brain lysates. This resulted in identification of murine GAD65 as the native autoantigen. GAD65 is a known humoral autoantigen in human type 1 diabetes mellitus (T1DM), but its existence in mice had been controversial. This study demonstrates the potential of this chemical approach for the unbiased identification of autoantigen/autoantibody complexes.

  3. 25-hydroxyvitamin D, autoantigenic and total antibody concentrations

    DEFF Research Database (Denmark)

    Thorsen, Steffen Ullitz; Pipper, Christian B; Johannesen, Jesper

    2018-01-01

    conducted within this field. OBJECTIVE: Our objective was to investigate if higher 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma associated antigen-2A (IA-2A). Further, we also wanted to examine......BACKGROUND: B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been...... the relationship between 25(OH)D and total antibody concentrations. METHODS: We randomly selected 500 patients with newly diagnosed T1D and 500 siblings for 25(OH)D, antibody and genetic analysis from the population-based Danish Registry of Childhood and Adolescent Diabetes. The relative change (RC) in the mean...

  4. Investigations of Caspr2, an autoantigen of encephalitis and neuromyotonia

    Science.gov (United States)

    Lancaster, Eric; Huijbers, Maartje GM; Bar, Vered; Boronat, Anna; Wong, Andrew; Martinez-Hernandez, Eugenia; Wilson, Christina; Jacobs, Dina; Lai, Meizan; Walker, Russell W; Graus, Francesc; Bataller, Luis; Illa, Isabel; Markx, Sander; Strauss, Kevin A.; Peles, Elior; Scherer, Steven S; Dalmau, Josep

    2010-01-01

    Objective To report clinical and immunological investigations of contactin-associated protein-like 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC). Methods Clinical analysis of patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity. Results Using Caspr2-expressing cells, antibodies were identified in 8 patients but not in 140 patients with several types of autoimmune or viral encephalitis, PNH, or mutations of the Caspr2-encoding gene. Patients’ antibodies reacted with brain and peripheral nerve in a pattern that co-localized with Caspr2. This reactivity was abrogated after immunoabsorption with Caspr2 and was absent in tissues from Caspr2-null mice. Of the 8 patients with Caspr2 antibodies, 7 had encephalopathy or seizures, 5 neuropathy or PNH, and 1 isolated PNH. Three patients had also myasthenia gravis, bulbar weakness, or symptoms that initially suggested motor neuron disease. None of the patients had active cancer; 7 responded to immunotherapy and were healthy or only mildly disabled at last follow-up (median 8 months, range 6–84). Interpretation Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. The occurrence of other autoantibodies may result in a complex syndrome that at presentation could be mistaken for a motor neuron disorder. Recognition of this disorder is important because it responds to immunotherapy. PMID:21387375

  5. [Studies on calf salmonellosis. 4. Oral and parenteral immunization with live (Smd) and killed antigens].

    Science.gov (United States)

    Meyer, H; Steinbach, G; Hartmann, H; Hauke, H; Koch, H; Stelzner, A; Linde, K; Schmerbauch, A; Kiupel, H

    1977-01-01

    Reported are results obtained from studies into oral and parenteral immunisation of calf. The approaches had included the use of live (Smd) or dead antigen from Salmonella (S.) dublin and a combination of the two immunisation methods. Live antigen (Smd) was superior to thermally activated dead antigen, when the oral route was used to prevent S.-dublin injection of calves. The above findings were supported by results from analogous studies in which S. typhimurium and S. dublin or live antigen (Smd) or dead antigen, made of the two, had been applied to mice. (One single subcutaneous) parenteral administration did hardly reveal any difference in favour of live vaccine (Smd). Parenteral administration of live or dead antigen proved to be less effective than repeated oral immunisation, particularly when live vaccine (Smd) was used. Immunity not less than up to six months of age against S. dublin wild strain infection can be provided for young calves by oral immunisation, with Smd vaccine (5. 1010 to 1. 1011 live germs/d) being given on ten consecutive days. Calves orally immunised with live antigen (ten repetitive applications of Smd mutants) are likely to develop an antibody titre (H-agglutinins) against S. dublin. Parenteral boostering,using live antigen, has been accompanied by sensitisation due to oral live antigen administration as well as by dose dependence, as was seen from the bactericidal values. Sensitisation was established from orally immunised calves up to three months old (typical booster reaction). Some of it was attributabale to confrontation with wild strains of Salmonella. The H-agglutinin titres of animals aged threemonths in a calf herd with salmonelloses in which all animals had been orally Smd-immunised were close to those recorded from calves in stocks with no salmonellosis occurrence. Under the conditions of oral immunisation, there had obviously been no action of the wild strain which might have triggered intensive antibody formation.

  6. Autoantigens targeted in scleroderma patients with vascular disease are enriched in endothelial lineage cells

    Science.gov (United States)

    McMahan, Zsuzsanna H.; Cottrell, Tricia R.; Wigley, Fredrick M.; Antiochos, Brendan; Zambidis, Elias T.; Park, Tea Soon; Halushka, Marc K.; Gutierrez-Alamillo, Laura; Cimbro, Raffaello; Rosen, Antony; Casciola-Rosen, Livia

    2016-01-01

    Objective Scleroderma patients with autoantibodies to centromere proteins (CENPs) and/or interferon-inducible protein 16 (IFI16) are at increased risk of severe vascular complications. We set out to define whether these autoantigens are enriched in cells of the vasculature. Methods Successive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI16 and CD31 expression were defined in skin paraffin sections from scleroderma patients and from healthy controls. IFI16 expression was determined by flow cytometry in circulating endothelial cells (CECs) and circulating progenitor cells (CPCs). Results Expression of CENP-A, IFI16 and CD31 was enriched in EBs at days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI16, CD31, CENPs A and-B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of skin paraffin sections showed enrichment of IFI16 in CD31-positive vascular endothelial cells in biopsies from scleroderma patients and normal controls. Flow cytometry analysis revealed IFI16 expression in CPCs, but minimal expression in CECs. Conclusion Expression of scleroderma autoantigens IFI16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens. PMID:27159521

  7. Tools for Scientist Engagement in E/PO: NASA SMD Community Workspace and Online Resources

    Science.gov (United States)

    Dalton, H.; Shipp, S. S.; Grier, J.; Gross, N. A.; Buxner, S.; Bartolone, L.; Peticolas, L. M.; Woroner, M.; Schwerin, T. G.

    2014-12-01

    The Science Mission Directorate (SMD) Science Education and Public Outreach (E/PO) Forums are here to help you get involved in E/PO! The Forums have been developing several online resources to support scientists who are - or who are interested in becoming - involved in E/PO. These include NASA Wavelength, EarthSpace, and the SMD E/PO online community workspace. NASA Wavelength is the one-stop shop of all peer-reviewed NASA education resources to find materials you - or your audiences - can use. Browse by audience (pre-K through 12, higher education, and informal education) or topic, or choose to search for something specific by keyword and audience. http://nasawavelength.org. EarthSpace, an online clearinghouse of Earth and space materials for use in the higher education classroom, is driven by a powerful search engine that allows you to browse the collection of resources by science topic, audience, type of material or key terms. All materials are peer-reviewed before posting, and because all submissions receive a digital object identifier (doi), submitted materials can be listed as publications. http://www.lpi.usra.edu/earthspace. The SMD E/PO online community workspace contains many resources for scientists. These include one-page guides on how to get involved, tips on how to make the most of your time spent on E/PO, and sample activities, as well as news on funding, policy, and what's happening in the E/PO community. The workspace also provides scientists and the public pathways to find opportunities for participation in E/PO, to learn about SMD E/PO projects and their impacts, to connect with SMD E/PO practitioners, and to explore resources to improve professional E/PO practice, including literature reviews, information about the Next Generation Science Standards, and best practices in evaluation and engaging diverse audiences. http://smdepo.org.

  8. Validation of accuracy and reliability of a simple measurement device for the lumber range of motion (SMD-L-ROM)

    International Nuclear Information System (INIS)

    Kato, Nakayuki; Fujiwara, Atsushi; Honda, Toshio; Taneichi, Hiroshi

    2007-01-01

    It is important to evaluate mobility of the lumbar spine for assessment of lumbar spinal disorders and their therapeutic effects. We developed a simple measurement device for the lumbar range of motion (SMD-L-ROM) which can be installed on the trunk. SMD-L-ROM allows to evaluate mobility of the lumbar spine without x-ray exposure. Accuracy and reliability of the measurement device was assessed in this article. SMD-L-ROM comprises two metallic immobilization plates (IPs) with a vertically installed bar and a rubber band for fixation of IP to the trunk. Two IPs were installed at the level of Th12 and the sacrum. Range of motion (ROM) of the lumbar spine was measured by using SMD-L-ROM and radiographic modalities (X-ray and CT). Consistency of the measured values by both of SMD-L-ROM and radiographic modalities was evaluated. Furthermore, inter- and intra-observer agreement of measured values by SMD-L-ROM was assessed. Regarding measurement of ROM, there was a high correlation between SMD-L-ROM and X-ray/CT especially in the sagittal and axial plane. There was no significant difference in the average values of ROM between the two methods. On the other hand, SMD-L-ROM did not detect accurate position of the lumbar spine in all dimensions. There were no inter- and intra-observer errors of measured values by SMD-L-ROM. ROM of the lumbar spine was simply and economically measured with SMD-L-ROM. Accuracy and reliability of SMD-L-ROM was good enough for ROM measurement in the lumbar spine. (author)

  9. NASA SMD Airborne Science Capabilities for Development and Testing of New Instruments

    Science.gov (United States)

    Fladeland, Matthew

    2015-01-01

    The SMD NASA Airborne Science Program operates and maintains a fleet of highly modified aircraft to support instrument development, satellite instrument calibration, data product validation and earth science process studies. This poster will provide an overview of aircraft available to NASA researchers including performance specifications and modifications for instrument support, processes for requesting aircraft time and developing cost estimates for proposals, and policies and procedures required to ensure safety of flight.

  10. NASA's SMD Cross-Forum Resources for Supporting Scientist Engagement in Education and Public Outreach Activities

    Science.gov (United States)

    Buxner, S.; Cobabe-Ammann, E. A.; Hsu, B. C.; Sharma, M.; Peticolas, L. M.; Schwerin, T. G.; Shipp, S. S.; Smith, D.

    2012-12-01

    Sharing the excitement of ongoing scientific discoveries is an important aspect of scientific activity for researchers. Directly engaging scientists in education and public outreach (E/PO) activities has the benefit of directly connecting the public to those who engage in scientific activities. A shortage of training in education methods, public speaking, and working with various public audiences increases barriers to engaging scientists in these types in E/PO activities. NASA's Science Mission Directorate (SMD) Education and Public forums (astrophysics, earth science, heliophysics, and planetary science) support scientists currently involved in E/PO and who are interested in becoming involved in E/PO through a variety of avenues. Over the past three years, the forums have developed a variety of resources to help engage scientists in education and public outreach. We will showcase the following resources developed through the SMD E/PO cross-forum efforts: Professional development resources for writing NASA SMD E/PO proposals (webinars and other online tools), ongoing professional development at scientific conferences to increase scientist engagement in E/PO activities, toolkits for scientists interested in best practices in E/PO (online guides for K-12 education and public outreach), toolkits to inform scientists of science education resources developed within each scientific thematic community, EarthSpace (a community web space where instructors can find and share about teaching space and earth sciences in the undergraduate classroom, including class materials news and funding opportunities, and the latest education research, http://www.lpi.usra.edu/earthspace/), thematic resources for teaching about SMD science topics, and an online database of scientists interested in connecting with education programs. Learn more about the Forum and find resources at http://smdepo.org/.

  11. Expression of recombinant proteinase 3, the autoantigen in Wegener's granulomatosis, in insect cells

    NARCIS (Netherlands)

    Van der Geld, YM; Smook, MLF; Huitema, MG; Harmsen, MC; Limburg, PC; Kallenberg, CGM

    2002-01-01

    Proteinase 3 (PR3) is the major autoantigen for anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis. Little is known about the major antigenic sites on PR3. To facilitate epitope mapping, PR3 was cloned in insect cells using a baculovirus expression system. Four

  12. NASA SMD STEM Activation: Enabling NASA Science Experts and Content into the Learning Environment

    Science.gov (United States)

    Hasan, Hashima; Erickson, Kristen

    2018-01-01

    The NASA Science Mission Directorate (SMD) restructured its efforts to enhance learning in science, technology, engineering, and mathematics (STEM) content areas through a cooperative agreement notice issued in 2015. This effort resulted in the competitive selection of 27 organizations to implement a strategic approach that leverages SMD’s unique assets. Three of these are exclusively directed towards Astrophysics. These unique assets include SMD’s science and engineering content and Science Discipline Subject Matter Experts. Awardees began their work during 2016 and span all areas of Earth and space science and the audiences NASA SMD intends to reach. The goal of the restructured STEM Activation program is to further enable NASA science experts and content into the learning environment more effectively and efficiently with learners of all ages. The objectives are to enable STEM education, improve US scientific literacy, advance national educational goals, and leverage efforts through partnerships. This presentation will provide an overview of the NASA SMD STEM Activation landscape and its commitment to meeting user needs.

  13. [Implementation and evaluation of case management in Catalonia: the ISP-SMD program].

    Science.gov (United States)

    Balsera Gómez, J; Rodríguez Medina, C; Caba Calvet, R; Vega Prada, R; Ruiz Ureña, H; Berruezo Ortiz, L; Clusa Gironella, D; Rodríguez Montes, M J; Haro Abad, J M

    2002-01-01

    The pilot study of the Individualized Service Program for people with Severe Mental Disorders (ISP-SMD) consists of the implementation of case management services in Catalonia. The ISP-SMD has been implemented in two health care sectors and will be expanded to the rest of Catalonia in the next years. The program serves people with persistent mental disorders who have serious social or family problems and/or who have inadequate mental health service use (high use of inpatient services, no use of community services). The ISP-SMD is a community intervention program that focuses its activities on direct care and coordination between services. Thirty patients have been included in the evaluation. The results of the pilot study have shown that, compared to the year before entering the program, the patients show better clinical status, they decrease their unmet need level, they have more appropriate use of health services and have lower treatment costs. Satisfaction of the patients, family members and professionals with the program is very high. It is possible to adapt and implement case management services in Catalonia. When implemented, they improve patient quality of life.

  14. Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

    Directory of Open Access Journals (Sweden)

    Rajwahrdhan Yadav

    2010-08-01

    Full Text Available Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards

  15. Resources from the NASA SMD Astrophysics Forum: Addressing the needs of the higher education community (Invited)

    Science.gov (United States)

    Meinke, B. K.; Schultz, G. R.; Smith, D.; Bianchi, L.; Blair, W. P.; Fraknoi, A.

    2013-12-01

    Four NASA Science Mission Directorate (SMD) Science Education and Public Outreach Forums organize individual SMD-funded E/PO projects and their teams into a coordinated effort. The Forums assist scientists and educators with becoming involved in SMD E/PO and make SMD E/PO resources and expertise accessible to the science and education communities. The Astrophysics Forum and the Astrophysics E/PO community have focused efforts to support and engage the higher education community on enhancing awareness of the resources available to them. To ensure Astrophysics higher education efforts are grounded in audience needs, we held informal conversations with instructors of introductory astronomy courses, convened sessions with higher education faculty and E/PO professionals at conferences, and examined existing literature and findings of the SMD Higher Education Working Group. This work indicates that most Astronomy 101 instructors are not specialists in areas of astrophysics where rapid progress is being made, older textbooks are out of date, and ideas are challenging for students. Instructors are seeking resources and training that support them in effectively teaching the latest science and are in need both basic material and information on new results. In this session, we will discuss our efforts to address these expressed needs, namely through Resource Guides and Slide Sets, and how these are applicable to topics in Heliophysics and Planetary Science. We have collaborated with the Astrophysics E/PO community, researchers, and Astronomy 101 instructors to create two Resource Guides on the topics of cosmology and exoplanets. These fields are ripe with scientific developments that college instructors have told us they find challenging to stay current. Each guide includes a wide variety of sources of background information, links to animations/simulations, classroom activities, and references on teaching each topic. Feedback from Astronomy 101 instructors indicated that the

  16. Dosimetric analysis of SMD phototransistor in dental phantom of different geometries

    International Nuclear Information System (INIS)

    Belinato, W.; Magalhaes, C. M. S.; Souza, D. N.; Santos, L. A. P.

    2009-10-01

    A commercial surface mount device (SMD) phototransistor, OP520, was inserted in two dental phantoms for dosimetric analysis. The irradiations were accomplished in a dental x-ray equipment of 80 kV using different exposition times. A standard ionization chamber was irradiated at the same conditions and the air kerma measured with it was compared with the electrical charge evaluated by the phototransistor. The results showed satisfactory correspondence among the detectors readings. Moreover, the phototransistor showed up quite sensitively for dental applications, allowing verifying the variations for the different phantoms configurations. (Author)

  17. Solar Electric Propulsion (SEP) Systems for SMD Mission Needs. Technology Infusion Study.

    Science.gov (United States)

    Anderson, David

    2014-01-01

    Two presentations for SBAG and OPAG meetings: 1) Solar Electric Propulsion Systems for SMD Missions, and 2) Technology Infusion Study - Draft Findings Recommendation Small Bodies Assessment Group (SBAG) meeting is January 9th in Washington D.C., and the Outer Planets Assessment Group (OPAG) meeting is January 23-14 in Tucson, AZ. NASA sponsors these assessment groups, through the NRC, for the science community to assess and provide advice. These talks are to provide a status of 2 NASA activities, and to seek feedback from the respective science communities.

  18. Dysregulated homeostasis of target tissues or autoantigens - A novel principle in autoimmunity.

    Science.gov (United States)

    Petersen, Frank; Yue, Xiaoyang; Riemekasten, Gabriela; Yu, Xinhua

    2017-06-01

    Monogenic autoimmune disorders provide a powerful tool for our understanding of the principles of autoimmunity due to the obvious impact of a single gene on the disease. So far, approximately 100 single gene defects causing murine monogenic autoimmune disorders have been reported and the functional characterization of these genes will provide significant progress in understanding the nature of autoimmunity. According to their function, genes leading to monogenic autoimmune disorders can be categorized into two groups. An expectable first group contains genes involved in the homeostasis of the immune system, including homeostasis of immune organs and immune cells. Intriguingly, the second group consists of genes functionally involved in the homeostasis of target tissues or autoantigens. According to our novel hypothesis, we propose that autoimmunity represents a consequence of a dysregulated homeostasis of the immune system and/or its targets including autoantigens and target tissues. In this review we refer to both aspects of homeostasis in autoimmunity with a highlight on the role of the homeostasis of target tissues and autoantigens. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Neutrophil Extracellular DNA Traps Induce Autoantigen Production by Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Youngwoo Choi

    2017-01-01

    Full Text Available The hypothesis of autoimmune involvement in asthma has received much recent interest. Autoantibodies, such as anti-cytokeratin (CK 18, anti-CK19, and anti-α-enolase antibodies, react with self-antigens and are found at high levels in the sera of patients with severe asthma (SA. However, the mechanisms underlying autoantibody production in SA have not been fully determined. The present study was conducted to demonstrate that neutrophil extracellular DNA traps (NETs, cytotoxic molecules released from neutrophils, are a key player in the stimulation of airway epithelial cells (AECs to produce autoantigens. This study showed that NETs significantly increased the intracellular expression of tissue transglutaminase (tTG but did not affect that of CK18 in AECs. NETs induced the extracellular release of both tTG and CK18 in a concentration-dependent manner. Moreover, NETs directly degraded intracellular α-enolase into small fragments. However, antibodies against neutrophil elastase (NE or myeloperoxidase (MPO attenuated the effects of NETs on AECs. Furthermore, each NET isolated from healthy controls (HC, nonsevere asthma (NSA, and SA had different characteristics. Taken together, these findings suggest that AECs exposed to NETs may exhibit higher autoantigen production, especially in SA. Therefore, targeting of NETs may represent a new therapy for neutrophilic asthma with a high level of autoantigens.

  20. SmD1 Modulates the miRNA Pathway Independently of Its Pre-mRNA Splicing Function.

    Directory of Open Access Journals (Sweden)

    Xiao-Peng Xiong

    2015-08-01

    Full Text Available microRNAs (miRNAs are a class of endogenous regulatory RNAs that play a key role in myriad biological processes. Upon transcription, primary miRNA transcripts are sequentially processed by Drosha and Dicer ribonucleases into ~22-24 nt miRNAs. Subsequently, miRNAs are incorporated into the RNA-induced silencing complexes (RISCs that contain Argonaute (AGO family proteins and guide RISC to target RNAs via complementary base pairing, leading to post-transcriptional gene silencing by a combination of translation inhibition and mRNA destabilization. Select pre-mRNA splicing factors have been implicated in small RNA-mediated gene silencing pathways in fission yeast, worms, flies and mammals, but the underlying molecular mechanisms are not well understood. Here, we show that SmD1, a core component of the Drosophila small nuclear ribonucleoprotein particle (snRNP implicated in splicing, is required for miRNA biogenesis and function. SmD1 interacts with both the microprocessor component Pasha and pri-miRNAs, and is indispensable for optimal miRNA biogenesis. Depletion of SmD1 impairs the assembly and function of the miRISC without significantly affecting the expression of major canonical miRNA pathway components. Moreover, SmD1 physically and functionally associates with components of the miRISC, including AGO1 and GW182. Notably, miRNA defects resulting from SmD1 silencing can be uncoupled from defects in pre-mRNA splicing, and the miRNA and splicing machineries are physically and functionally distinct entities. Finally, photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP analysis identifies numerous SmD1-binding events across the transcriptome and reveals direct SmD1-miRNA interactions. Our study suggests that SmD1 plays a direct role in miRNA-mediated gene silencing independently of its pre-mRNA splicing activity and indicates that the dual roles of splicing factors in post-transcriptional gene regulation may be

  1. A La autoantigen homologue is required for the internal ribosome entry site mediated translation of giardiavirus.

    Directory of Open Access Journals (Sweden)

    Srinivas Garlapati

    2011-03-01

    Full Text Available Translation of Giardiavirus (GLV mRNA is initiated at an internal ribosome entry site (IRES in the viral transcript. The IRES localizes to a downstream portion of 5' untranslated region (UTR and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of trans-activating protein factors. A La autoantigen homologue in the viral host Giardia lamblia, GlLa, was proposed as one of the potential trans-activating factors based on its specific binding to GLV-IRES in vitro. In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in Giardia by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in Giardia moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA, known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities in vitro and in vivo, was also found to bind to GlLa protein in vitro and inhibited GLV-IRES function in vivo. The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200-348aa of GlLa in Giardia showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of Giardia, thus supporting a primary role of GlLa in translation initiation in Giardiavirus.

  2. A new optimization approach for nozzle selection and component allocation in multi-head beam-type SMD placement machines

    NARCIS (Netherlands)

    Torabi, S.A.; Hamedi, M.; Ashayeri, J.

    2013-01-01

    This paper addresses a highly challenging scheduling problem faced in multi-head beam-type surface mounting devices (SMD) machines. An integrated mathematical model is formulated aiming to balance workloads over multiple heads as well as improving the traveling speed of the robotic arm by

  3. Software Design of SMD LEDs for Homogeneous Distribution of Irradiation in the Model of Dark Room

    Directory of Open Access Journals (Sweden)

    Andrej Liner

    2014-01-01

    Full Text Available This article describes wireless optical data networks using visible spectra of optical radiation with a focus on interior areas with direct line of sight LOS (line-of-sight. This type of network represents progressively evolving area of information technologies. Development of lightning technologies based on white power LED was the impulse for wireless optical data networks based on visible spectra of optical radiation (VLC development. Its basic advantage is the flexibility of users. Users don’t have to stay on one place during the data sharing anymore. Wireless optical data networks represent an alternative solution for metallic and fiber networks [1], [2]. This paper deals with the software simulation of homogeneous distribution of optical irradiation in dark room model, carrying out in LightTools software. First, in previous simulations, the optical source composed from 9 SMD LED’s type LW G6SP-EAFA-JKQL-1 was designed. In various simulations, various numbers and distributions of LED’s were used. These were placed at the ceiling of the dark room. At last, the results of optical irradiation homogeneity are compared.

  4. Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens

    Science.gov (United States)

    Lech, Maciej; Kulkarni, Onkar P.; Pfeiffer, Stephanie; Savarese, Emina; Krug, Anne; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

    2008-01-01

    The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice. PMID:18644972

  5. Review of autoantigens in Sjögren’s syndrome: an update

    Directory of Open Access Journals (Sweden)

    Tong L

    2017-08-01

    Full Text Available Louis Tong,1–4 Vanessa Koh,3 Bernard Yu-Hor Thong5 1Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 2Corneal and External Eye Disease, Singapore National Eye Centre, 3Ocular Surface Research Group, Singapore Eye Research Institute, 4Eye Academic Clinical Program, Duke-NUS Medical School, 5Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore Abstract: Primary Sjögren’s syndrome (pSS is an autoimmune disease characterized by inflammation in exocrine glands, resulting in reduced secretion of tears and saliva, manifesting as xerophthalmia and xerostomia, respectively. It is commonly associated with Sjögren’s syndrome type A (Ro and Sjögren’s syndrome type B (La antigens. However, in most patients, the identity of the triggering antigen is not known. Factors such as genetics of histocompatibility, dysregulation of T-cells, B-cells and viral infections have been implicated. Several important studies on autoantigens in pSS have been published since a review in 2012, and the aim of this review is to provide an update on further peer-reviewed original articles in this field. Oxidative damage of Ro60 antigen may explain the epitope spreading during the immune activation in pSS. Immune-mediated destruction of the muscarinic receptor-3-expressing cells has been associated with a reduction in parasympathetic function, which could cause reduced secretory function of exocrine glands. Such a process also activates reactive oxidative species and antioxidants, which are linked to the triggering of inflammatory responses. Elevated levels of kallikrein, yet another antigen present in the lacrimal gland and other tissues, are similarly involved in triggering an autoimmune T-cell response against target glands. Studying additional antigens, the platelet-selectin and vasoactive intestinal peptides, in patients with pSS can help to elucidate the origin and process of

  6. Amniotic Fluid Soluble Myeloid Differentiation-2 (sMD-2) as Regulator of Intra-amniotic Inflammation in Infection-induced Preterm Birth.

    Science.gov (United States)

    Dulay, Antonette T; Buhimschi, Catalin S; Zhao, Guomao; Oliver, Emily A; Abdel-Razeq, Sonya S; Shook, Lydia L; Bahtiyar, Mert O; Buhimschi, Irina A

    2015-06-01

    TLR4 mediates host responses to pathogens through a mechanism that involves protein myeloid differentiation-2 (MD-2) and its soluble form sMD-2. The role of sMD2 in intra-amniotic inflammation-induced preterm birth has not been previously explored. Human amniotic fluid (AF) sMD-2 was studied by Western blotting in 152 AF samples of patients who had an amniocentesis to rule-out infection (yes infection, n = 50; no infection, n = 50) or women with normal pregnancy outcome (second trimester genetic karyotyping, n = 26; third trimester lung maturity testing, n = 26). Histological localization and mRNA expression of MD2 in fetal membranes were studied by immunohistochemistry and RT-PCR. The ability of fetal membrane to release sMD-2 and inflammatory cytokines was studied in vitro. Human AF contains three sMD-2 proteoforms whose levels of expression were lower at term. Intra-amniotic infection upregulated sMD-2. MD-2 mRNA and immunohistochemistry findings concurred. In vitro, LPS and monensin increased, while cycloheximide decreased sMD-2 production. Recombinant sMD-2 modulated TNF-α and IL-6 levels in a dose- and time-dependent fashion. sMD2 proteoforms are constitutively present in human AF. The intensity of the intra-amniotic inflammatory response to bacteria or perhaps to other TLR4 ligands may be facilitated through synthesis and release of sMD2 by the amniochorion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis.

    Science.gov (United States)

    Choudhuri, K; Gregorio, G V; Mieli-Vergani, G; Vergani, D

    1998-11-01

    We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.

  8. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    International Nuclear Information System (INIS)

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E.

    1988-01-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M r 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects

  9. Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

    Science.gov (United States)

    Mujtaba, Muhammad Ahmad; Fridell, Jonathan; Book, Benita; Faiz, Sara; Sharfuddin, Asif; Wiebke, Eric; Rigby, Mark; Taber, Tim

    2015-11-01

    Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Review of autoantigens in Sjögren's syndrome: an update.

    Science.gov (United States)

    Tong, Louis; Koh, Vanessa; Thong, Bernard Yu-Hor

    2017-01-01

    Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by inflammation in exocrine glands, resulting in reduced secretion of tears and saliva, manifesting as xerophthalmia and xerostomia, respectively. It is commonly associated with Sjögren's syndrome type A (Ro) and Sjögren's syndrome type B (La) antigens. However, in most patients, the identity of the triggering antigen is not known. Factors such as genetics of histocompatibility, dysregulation of T-cells, B-cells and viral infections have been implicated. Several important studies on autoantigens in pSS have been published since a review in 2012, and the aim of this review is to provide an update on further peer-reviewed original articles in this field. Oxidative damage of Ro60 antigen may explain the epitope spreading during the immune activation in pSS. Immune-mediated destruction of the muscarinic receptor-3-expressing cells has been associated with a reduction in parasympathetic function, which could cause reduced secretory function of exocrine glands. Such a process also activates reactive oxidative species and antioxidants, which are linked to the triggering of inflammatory responses. Elevated levels of kallikrein, yet another antigen present in the lacrimal gland and other tissues, are similarly involved in triggering an autoimmune T-cell response against target glands. Studying additional antigens, the platelet-selectin and vasoactive intestinal peptides, in patients with pSS can help to elucidate the origin and process of autoimmunity, or even lead to potential biomarkers. In conclusion, the understanding of autoantigens has led to exciting major advances in the biology of pSS and may influence diagnosis and management of pSS in future.

  11. Differential diagnosis of sensory modulation dysfunction (SMD and attention deficit hyperactivity disorder (ADHD: participation, sensation and attention

    Directory of Open Access Journals (Sweden)

    Aviva eYochman

    2013-12-01

    Full Text Available Differential diagnosis between sensory modulation disorder (SMD and attention deficit hyperactivity disorder (ADHD is often challenging, since these disorders occur at a high rate of co-morbidity and share several clinical characteristics. Preliminary studies providing evidence that these are distinct disorders have focused solely on body functions, using sophisticated laboratory measurements. Moreover, no studies have compared participation profiles of these populations. This study is the first to compare the profiles of these populations regarding both ‘body functions’(attention and sensation and ‘participation,’ using measures applicable for clinical use. The study included 19 children with ADHD without SMD and 19 with SMD without ADHD (diagnosed by both pediatric neurologists and occupational therapists, aged 6 to 9, and matched by age and gender. All children underwent a broad battery of evaluations: The Evaluation of Sensory Processing, Fabric Prickliness Test and Von Frey Test to evaluate sensory processing, and Test of Everyday Attention to evaluate attention components. The Participation in Childhood Occupations Questionnaire was used to evaluate participation. Results support significant group differences in all sensory components, including pain intensity to suprathreshold stimuli and pain 'after sensation', as well as in tactile, vestibular, taste and olfactory processing. No differences were found in attention components and participation. This study has both theoretical and clinical importance, inter alia, providing further evidence of two distinct disorders as well as indications of specific clinical instruments that might enable clinicians to implement differential diagnoses. In addition, results accord with other previous statements, which indicate that the clinical diagnosis of children with disabilities may not be a major factor in determining their participation profile.

  12. Apoptosis and Redistribution of the Ro Autoantigen in Balb/c Mouse Like in Subacute Cutaneous Lupus Erythematosus

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    Rafael Herrera-Esparza

    2006-01-01

    Full Text Available In subacute cutaneous lupus eryhematosus (SCLE the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2 equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.

  13. Antibodies against linear epitopes on Goodpasture autoantigen in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

    Science.gov (United States)

    Jia, Xiao-Yu; Yu, Jun-Tao; Hu, Shui-Yi; Li, Jian-Nan; Wang, Miao; Wang, Chen; Chen, Min; Cui, Zhao; Zhao, Ming-Hui

    2017-09-01

    In a substantial number of patients with crescentic glomerulonephritis, both anti-glomerular basement membrane (GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA) are detected simultaneously. ANCA is presumed to be the initial event but the mechanism is unknown. In the present study, we investigated the antibodies against linear epitopes on Goodpasture autoantigen in sera from patients with ANCA-associated vasculitis, aiming to reveal the mechanisms of the coexistence of the two kinds of autoantibodies. Thirty-one patients with ANCA-associated vasculitis were enrolled in this study. Twenty-four overlapping linear peptides were synthesized across the whole sequence of Goodpasture autoantigen. Serum antibodies against linear peptides were detected by ELISA and their associations with clinical features were further analyzed. Twenty-five out of the thirty-one (80.6%) sera from patients with ANCA-associated vasculitis possessed antibodies against linear peptides on Goodpasture autoantigen. These antibodies could be detected in 50% of patients with normal renal function (Scr ≤ 133 μmol/L), 70% of patients with moderate renal dysfunction (133 μmol/L  600 μmol/L) (P = 0.032). The highest recognition frequencies were found for peptides P4 (51.6%), P14 (54.8%), and P24 (54.8%), which contained the sequences that constitute the conformational epitopes of E A (P4) and E B (P14) recognized by anti-GBM antibodies. The level of anti-P4 antibodies was positively correlated with the percentage of crescents in glomeruli (r = 0.764, P = 0.027). Patients with anti-P24 antibodies had a significantly higher prevalence of renal dysfunction on diagnosis (88.2 vs. 42.9%, P = 0.018). Antibodies against linear epitopes on Goodpasture autoantigen could be detected in sera of patients with ANCA-associated vasculitis, which might mediate the production of antibodies towards the conformational epitopes on Goodpasture autoantigen, namely, the anti-GBM antibodies.

  14. Design of a Type-1 Diabetes Vaccine Candidate Using Edible Plants Expressing a Major Autoantigen

    Directory of Open Access Journals (Sweden)

    Edoardo Bertini

    2018-05-01

    Full Text Available Type-1 diabetes (T1D is a metabolic disease involving the autoimmune destruction of insulin-producing pancreatic beta cells. It is often diagnosed by the detection of autoantibodies, typically those recognizing insulin itself or the 65-kDa isoform of glutamic acid decarboxylase (GAD65. Oral insulin can be used to induce systemic immunological tolerance and thus prevent or delay the onset of T1D, suggesting that combination treatments with other autoantigens such as GAD65 could be even more successful. GAD65 has induced oral tolerance and prevented T1D in preclinical studies but it is difficult to produce in sufficient quantities for clinical testing. Here we combined edible plant systems, namely spinach (Spinacia oleracea cv Industra and red beet (Beta vulgaris cv Moulin Rouge, with the magnICON® expression system to develop a safe, cost-effective and environmentally sustainable platform for the large-scale production of GAD65. The superior red beet platform was extensively characterized in terms of recombinant protein yields and bioequivalence to wild-type plants, and the product was tested for its ability to resist simulated gastric digestion. Our results indicate that red beet plants are suitable for the production of a candidate oral vaccine based on GAD65 for the future preclinical and clinical testing of T1D immunotherapy approaches.

  15. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells.

    Science.gov (United States)

    Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D; Herzog, Roland; Daniell, Henry

    2013-06-15

    Among 12billion injections administered annually, unsafe delivery leads to >20million infections and >100million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1 diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis.

    Science.gov (United States)

    Granito, Alessandro; Yang, Wei-Hong; Muratori, Luigi; Lim, Mark J; Nakajima, Ayako; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Bianchi, Francesco B; Bloch, Donald B; Muratori, Paolo

    2010-01-01

    Some patients with primary biliary cirrhosis (PBC) have antinuclear antibodies (ANAs). These ANAs include the "multiple nuclear dots" (MND) staining pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB) components, such as "speckled 100-kD" protein (Sp100) and PML. A new PML NB protein, designated as Sp140, was identified using serum from a PBC patient. The aim of this study was to analyze the immune response against Sp140 protein in PBC patients. We studied 135 PBC patients and 157 pathological controls with type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus erythematosus. We used indirect immunofluorescence and a neuroblastoma cell line expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially available immunoblot for detecting anti-Sp100 and anti-PML antibodies. Anti-Sp140 antibodies were present in 20 (15%) PBC patients but not in control samples, with a higher frequency in antimitochondrial antibody (AMA)-negative cases (53 vs. 9%, P<0.0001). Anti-Sp140 antibodies were found together with anti-Sp100 antibodies in all but one case (19 of 20, 90%) and with anti-PML antibodies in 12 (60%) cases. Anti-Sp140 positivity was not associated with a specific clinical feature of PBC. Our study identifies Sp140 as a new, highly specific autoantigen in PBC for the first time. The very frequent coexistence of anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a multiantigenic complex in PBC and enhances the diagnostic significance of these reactivities, which are particularly useful in AMA-negative cases.

  17. Identification of critical residues of linear B cell epitope on Goodpasture autoantigen.

    Directory of Open Access Journals (Sweden)

    Xiao-yu Jia

    Full Text Available The autoantigen of anti-glomerular basement membrane (GBM disease has been identified as the non-collagenous domain 1 of α3 chain of type IV collagen, α3(IVNC1. Our previous study revealed a peptide on α3(IVNC1 as a major linear epitope for B cells and potentially nephrogenic, designated as P14 (α3129-150. This peptide has also been proven to be the epitope of auto-reactive T cells in anti-GBM patients. This study was aimed to further characterize the critical motif of P14.16 patients with anti-GBM disease and positive anti-P14 antibodies were enrolled. A set of truncated and alanine substituted peptides derived from P14 were synthesized. Circulating antibodies against the peptides were detected by enzyme linked immunosorbent assay (ELISA.We found that all sera with anti-P14 antibodies reacted with the 13-mer sequence in the C-terminus of P14 (P14c exclusively. The level of antibodies against P14 was highly correlated with the level of antibodies against P14c (r=0.970, P<0.001. P14c was the core immunogenic region and the amino acid sequence (ISLWKGFSFIMFT was highly hydrophobic. Each amino acid residue in P14c was sequentially replaced by alanine. Three residues of glycine142, phenylalanine143, and phenylalanine145 were identified crucial for antibody binding based on the remarkable decline (P<0.001 of antibody reaction after each residue replacement.We defined GFxF (α3142, 143,145 as the critical motif of P14. It may provide some clues for understanding the etiology of anti-GBM disease.

  18. Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

    Directory of Open Access Journals (Sweden)

    Kostianets Olga

    2012-11-01

    Full Text Available Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

  19. Second Sound Measurement using SMD resistors to simulate Quench locations on the 704 MHZ Single-Cell Cavity at CERN

    CERN Document Server

    Liao, K; Ciapala, E; Junginger, T; Weingarten, W

    2012-01-01

    Oscillating Superleak Transducers (OSTs) containing flexible porous membranes are widely used to detect the so-called second sound temperature wave when a quench event occurs in a superconducting RF cavity. In principle, from the measured speed of this wave and the travel time between the quench event and several OSTs, the location of the quench sites can be derived by triangulation. Second sound behaviour has been simulated through different surface mount (SMD) resistors setups on a Superconducting Proton Linac (SPL) test cavity, to help understanding the underlying physics and improve quench localisation. Experiments are described that have been conducted to search for explanation of heat transfer during cavity quench that causes contradictory triangulation results.

  20. LmSmdB: an integrated database for metabolic and gene regulatory network in Leishmania major and Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Priyanka Patel

    2016-03-01

    Full Text Available A database that integrates all the information required for biological processing is essential to be stored in one platform. We have attempted to create one such integrated database that can be a one stop shop for the essential features required to fetch valuable result. LmSmdB (L. major and S. mansoni database is an integrated database that accounts for the biological networks and regulatory pathways computationally determined by integrating the knowledge of the genome sequences of the mentioned organisms. It is the first database of its kind that has together with the network designing showed the simulation pattern of the product. This database intends to create a comprehensive canopy for the regulation of lipid metabolism reaction in the parasite by integrating the transcription factors, regulatory genes and the protein products controlled by the transcription factors and hence operating the metabolism at genetic level. Keywords: L.major, S.mansoni, Regulatory networks, Transcription factors, Database

  1. Single-molecule dataset (SMD): a generalized storage format for raw and processed single-molecule data.

    Science.gov (United States)

    Greenfeld, Max; van de Meent, Jan-Willem; Pavlichin, Dmitri S; Mabuchi, Hideo; Wiggins, Chris H; Gonzalez, Ruben L; Herschlag, Daniel

    2015-01-16

    Single-molecule techniques have emerged as incisive approaches for addressing a wide range of questions arising in contemporary biological research [Trends Biochem Sci 38:30-37, 2013; Nat Rev Genet 14:9-22, 2013; Curr Opin Struct Biol 2014, 28C:112-121; Annu Rev Biophys 43:19-39, 2014]. The analysis and interpretation of raw single-molecule data benefits greatly from the ongoing development of sophisticated statistical analysis tools that enable accurate inference at the low signal-to-noise ratios frequently associated with these measurements. While a number of groups have released analysis toolkits as open source software [J Phys Chem B 114:5386-5403, 2010; Biophys J 79:1915-1927, 2000; Biophys J 91:1941-1951, 2006; Biophys J 79:1928-1944, 2000; Biophys J 86:4015-4029, 2004; Biophys J 97:3196-3205, 2009; PLoS One 7:e30024, 2012; BMC Bioinformatics 288 11(8):S2, 2010; Biophys J 106:1327-1337, 2014; Proc Int Conf Mach Learn 28:361-369, 2013], it remains difficult to compare analysis for experiments performed in different labs due to a lack of standardization. Here we propose a standardized single-molecule dataset (SMD) file format. SMD is designed to accommodate a wide variety of computer programming languages, single-molecule techniques, and analysis strategies. To facilitate adoption of this format we have made two existing data analysis packages that are used for single-molecule analysis compatible with this format. Adoption of a common, standard data file format for sharing raw single-molecule data and analysis outcomes is a critical step for the emerging and powerful single-molecule field, which will benefit both sophisticated users and non-specialists by allowing standardized, transparent, and reproducible analysis practices.

  2. Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

    Science.gov (United States)

    Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

    2015-01-01

    Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

  3. Aberrant accumulation of the diabetes autoantigen GAD65 in Golgi membranes in conditions of ER stress and autoimmunity

    DEFF Research Database (Denmark)

    Phelps, Edward A; Cianciaruso, Chiara; Michael, Iacovos P

    2016-01-01

    Pancreatic islet beta cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in beta cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in human T1D. GAD65 synthesizes GABA......, an important autocrine and paracrine signaling molecule and a survival factor in islets. We show that ER stress in primary beta cells perturbs the palmitoylation cycle controlling GAD65 endomembrane distribution, resulting in aberrant accumulation of the palmitoylated form in trans-Golgi membranes...... release from stressed and/or damaged beta cells, triggering autoimmunity....

  4. Production of the main celiac disease autoantigen by transient expression in Nicotiana benthamiana

    Directory of Open Access Journals (Sweden)

    Vanesa Soledad Marin Viegas

    2015-12-01

    Full Text Available Celiac Disease (CD is a gluten sensitive enteropathy that remains widely undiagnosed and implementation of massive screening tests is needed to reduce the long term complications associated to untreated CD. The main CD autoantigen, human tissue transglutaminase (TG2, is a challenge for the different expression systems available since its cross-linking activity affects cellular processes. Plant-based transient expression systems can be an alternative for the production of this protein. In this work, a transient expression system for the production of human TG2 in Nicotiana benthamiana leaves was optimized and reactivity of plant-produced TG2 in CD screening test was evaluated. First, a subcellular targeting strategy was tested. Cytosolic, secretory, endoplasmic reticulum (C-terminal SEKDEL fusion and vacuolar (C-terminal KISIA fusion TG2 versions were transiently expressed in leaves and recombinant protein yields were measured. ER-TG2 and vac-TG2 levels were 9 to 16 fold higher than their cytosolic and secretory counterparts. As second strategy, TG2 variants were co-expressed with a hydrophobic elastin-like polymer (ELP construct encoding for 36 repeats of the pentapeptide VPGXG in which the guest residue X were V and F in ratio 8:1. Protein bodies (PB were induced by the ELP, with a consequent 2 fold-increase in accumulation of both ER-TG2 and vac-TG2. Subsequently, ER-TG2 and vac-TG2 were produced and purified using immobilized metal ion affinity chromatography. Plant purified ER-TG2 and vac-TG2 were recognized by three anti-TG2 monoclonal antibodies that bind different epitopes proving that plant-produced antigen has immunochemical characteristics similar to those of human TG2. Lastly, an ELISA was performed with sera of CD patients and healthy controls. Both vac-TG2 and ER-TG2 were positively recognized by IgA of CD patients while they were not recognized by serum from non-celiac controls. These results confirmed the usefulness of plant

  5. Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen.

    Science.gov (United States)

    Alimohammadi, Mohammad; Dubois, Noémie; Sköldberg, Filip; Hallgren, Asa; Tardivel, Isabelle; Hedstrand, Håkan; Haavik, Jan; Husebye, Eystein S; Gustafsson, Jan; Rorsman, Fredrik; Meloni, Antonella; Janson, Christer; Vialettes, Bernard; Kajosaari, Merja; Egner, William; Sargur, Ravishankar; Pontén, Fredrik; Amoura, Zahir; Grimfeld, Alain; De Luca, Filippo; Betterle, Corrado; Perheentupa, Jaakko; Kämpe, Olle; Carel, Jean-Claude

    2009-03-17

    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  6. Theoretical prediction of pKa in methanol: testing SM8 and SMD models for carboxylic acids, phenols, and amines.

    Science.gov (United States)

    Miguel, Elizabeth L M; Silva, Poliana L; Pliego, Josefredo R

    2014-05-29

    Methanol is a widely used solvent for chemical reactions and has solvation properties similar to those of water. However, the performance of continuum solvation models in this solvent has not been tested yet. In this report, we have investigated the performance of the SM8 and SMD models for pKa prediction of 26 carboxylic acids, 24 phenols, and 23 amines in methanol. The gas phase contribution was included at the X3LYP/TZVPP+diff//X3LYP/DZV+P(d) level. Using the proton exchange reaction with acetic acid, phenol, and ammonia as reference species leads to RMS error in the range of 1.4 to 3.6 pKa units. This finding suggests that the performance of the continuum models for methanol is similar to that found for aqueous solvent. Application of simple empirical correction through a linear equation leads to accurate pKa prediction, with uncertainty less than 0.8 units with the SM8 method. Testing with the less expensive PBE1PBE/6-311+G** method results in a slight improvement in the results.

  7. Predicting cyclohexane/water distribution coefficients for the SAMPL5 challenge using MOSCED and the SMD solvation model

    Science.gov (United States)

    Diaz-Rodriguez, Sebastian; Bozada, Samantha M.; Phifer, Jeremy R.; Paluch, Andrew S.

    2016-11-01

    We present blind predictions using the solubility parameter based method MOSCED submitted for the SAMPL5 challenge on calculating cyclohexane/water distribution coefficients at 298 K. Reference data to parameterize MOSCED was generated with knowledge only of chemical structure by performing solvation free energy calculations using electronic structure calculations in the SMD continuum solvent. To maintain simplicity and use only a single method, we approximate the distribution coefficient with the partition coefficient of the neutral species. Over the final SAMPL5 set of 53 compounds, we achieved an average unsigned error of 2.2± 0.2 log units (ranking 15 out of 62 entries), the correlation coefficient ( R) was 0.6± 0.1 (ranking 35), and 72± 6 % of the predictions had the correct sign (ranking 30). While used here to predict cyclohexane/water distribution coefficients at 298 K, MOSCED is broadly applicable, allowing one to predict temperature dependent infinite dilution activity coefficients in any solvent for which parameters exist, and provides a means by which an excess Gibbs free energy model may be parameterized to predict composition dependent phase-equilibrium.

  8. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses Informal Educators' Preferences for PD and Materials

    Science.gov (United States)

    Bartolone, Lindsay; Nelson, Andi; Smith, Denise A.; NASA SMD Astrophysics E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of NASA Science Mission Directorate (SMD) Astrophysics EPO projects. These teams work together to capitalize on the cutting-edge discoveries of NASA Astrophysics missions to support educators in Science, Technology, Engineering, and Math (STEM) and to enable youth to engage in doing STEM inside and outside of school. The Astrophysics Forum assists scientists and educators with becoming involved in SMD E/PO, which is uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise, and makes SMD E/PO resources and expertise accessible to the science and education communities. Informal educators participated in a recent nationally-distributed survey from the NASA SMD SEPOF Informal Education Working Group. The results show the preferences of staff from museums, parks, public libraries, community/afterschool centers, and others with regard to professional development and material resources. The results of the survey will be presented during this session.In addition, we present opportunities for the astronomy community to participate in collaborations supporting the NASA SMD efforts in K-12 Formal Education, Informal Science Education, and Outreach. These efforts focus on enhancing instruction, as well as youth and public engagement, in STEM via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences. The Forums' efforts for the Formal, Informal Science Education and Outreach communities include a literature review, appraisal of informal educators' needs, coordination of audience-based NASA resources and opportunities, professional development, plus support with the Next Generation Science Standards. Learn how to join in our collaborative efforts to support the K-12 Formal Education community and to reach the informal

  9. Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice.

    Science.gov (United States)

    Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul; Daniell, Henry; Schatz, Desmond A; Atkinson, Mark A

    2017-02-13

    Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3 + and LAP + regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy. Recently, dogma was challenged in a report demonstrating oral insulin does not prevent T1D in NOD mice, possibly due to antigen digestion prior to mucosal immune exposure. We used transplastomic plants expressing proinsulin and GAD to protect the autoantigens from degradation in an oral vaccine and tested the optimal combination, dose, and treatment duration for the prevention of T1D in NOD mice. Our data suggest oral autoantigen therapy alone does not effectively influence disease incidence or result in antigen-specific tolerance assessed by IL-10 measurement and Treg frequency. A more aggressive approach involving tolerogenic cytokine administration and/or lymphocyte depletion prior to oral antigen-specific immunotherapy will likely be required to impart durable therapeutic efficacy.

  10. Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes cross-react with an epitope from the auto-antigen SS56

    DEFF Research Database (Denmark)

    Baek Sørensen, Rikke; Faurschou, Mikkel; Troelsen, Lone

    2009-01-01

    A large proportion of melanoma patients host a spontaneous T-cell response specifically against ML-IAP-derived peptides. In this study, we describe that some ML-IAP-specific cytotoxic T cells isolated from melanoma patients cross react with an epitope from the auto-antigen SS56. SS56 is a recentl...

  11. Mammalian peptidylglycine alpha-amidating monooxygenase (PAM) mRNA expression can be modulated by the La autoantigen

    DEFF Research Database (Denmark)

    Brenet, Fabienne; Dussault, Nadège; Borch, Jonas

    2005-01-01

    Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal alpha-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3' untranslated...... region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3' UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt...... downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3' UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most...

  12. 64,000-Mr autoantigen in type I diabetes. Evidence against its surface location on human islets

    International Nuclear Information System (INIS)

    Colman, P.G.; Campbell, I.L.; Kay, T.W.; Harrison, L.C.

    1987-01-01

    The sera of type I (insulin-dependent) diabetic subjects are reported to contain autoantibodies against a 64,000-Mr protein identified in [ 35 S]methionine biosynthetically labeled pancreatic islet cells. We have attempted to localize this autoantigen to the surface of the beta-cell and to define its properties. Sera from 10 newly diagnosed type I diabetic subjects, including five of the index sera originally used to identify the autoantigen, were shown to specifically precipitate a reduced protein of 67,000 Mr from Triton-solubilized, surface 125 I-labeled cultured adult human islet and rat insulinoma (RINm5F) cells but not from fresh rat spleen cells. Further characterization revealed that this protein was bovine serum albumin (BSA) adsorbed to cells from fetal calf serum (FCS)-supplemented culture medium and precipitated by BSA antibodies present in many diabetic sera. No labeled proteins were specifically precipitated when surface 125 I-labeled and solubilized human islet or RINm5F cells were precleared with anti-BSA immunoglobulins or when cells were first cultured in human serum. In contrast, a 64,000-Mr protein, clearly not BSA, was precipitated by diabetic globulins from human islets but not from RINm5F cells labeled with [ 35 S]methionine. In addition, a protein of the same size as well as proteins of approximately 35,000, 43,000, 140,000, and 200,000 Mr were specifically precipitated by diabetic globulins from freshly isolated human islets solubilized in Triton X-100 and then labeled with 125 I. These findings suggest that the 64,000-Mr antigen is not expressed on the surface of human islet cells, at least in culture, and therefore question its relevance as a target for islet cell surface antibodies in initiating beta-cell damage

  13. Evaluation of current and temperature effects on optical performance of InGaAlP thin-film SMD LED mounted on different substrate packages

    International Nuclear Information System (INIS)

    Raypah, Muna E.; Devarajan, Mutharasu; Sulaiman, Fauziah

    2017-01-01

    The relationship between the photometric, electric, and thermal parameters of light-emitting diodes (LEDs) is important for optimizing the LED illumination design. Indium gallium aluminium phosphide (InGaAlP)-based thin-film surface-mounted device (SMD) LEDs have attracted wide attention in research and development due to their portability and miniaturization. We report the optical characterization of InGaAlP thin-film SMD LED mounted on FR4, 2 W, and 5 W aluminum (Al) packages. The optical and thermal parameters of LED are determined at different injection currents and ambient temperatures by combining the T3ster (thermal transient tester) and TeraLED (thermal and radiometric characterization of power LEDs) systems. Analysis shows that LED on a 5 W Al substrate package obtains the highest luminous and optical efficiency. (paper)

  14. Performance of the SMD and SM8 models for predicting solvation free energy of neutral solutes in methanol, dimethyl sulfoxide and acetonitrile

    Science.gov (United States)

    Zanith, Caroline C.; Pliego, Josefredo R.

    2015-03-01

    The continuum solvation models SMD and SM8 were developed using 2,346 solvation free energy values for 318 neutral molecules in 91 solvents as reference. However, no solvation data of neutral solutes in methanol was used in the parametrization, while only few solvation free energy values of solutes in dimethyl sulfoxide and acetonitrile were used. In this report, we have tested the performance of the models for these important solvents. Taking data from literature, we have generated solvation free energy, enthalpy and entropy values for 37 solutes in methanol, 21 solutes in dimethyl sulfoxide and 19 solutes in acetonitrile. Both SMD and SM8 models have presented a good performance in methanol and acetonitrile, with mean unsigned error equal or less than 0.66 and 0.55 kcal mol-1 in methanol and acetonitrile, respectively. However, the correlation is worse in dimethyl sulfoxide, where the SMD and SM8 methods present mean unsigned error of 1.02 and 0.95 kcal mol-1, respectively. Our results point out the SMx family of models need be improved for dimethyl sulfoxide solvent.

  15. Improved catalytic efficiency, thermophilicity, anti-salt and detergent tolerance of keratinase KerSMD by partially truncation of PPC domain.

    Science.gov (United States)

    Fang, Zhen; Zhang, Juan; Du, Guocheng; Chen, Jian

    2016-06-14

    The keratinase from Stenotrophomonas maltophilia (KerSMD) is known for its high activity and pH stability in keratin degradation. However, catalytic efficiency and detergent tolerability need to be improved in order to be used for industrial application. In this work, we obtained several keratinase variants with enhanced catalytic efficiency, thermophilicity, and anti-salt and detergent tolerability by partially truncating the PPC domain of KerSMD. The variants all showed improved catalytic efficiency to synthetic substrate AAPF, with the V355 variant having the highest kcat /Km value of 143.6 s(-1) mM(-1). The truncation of keratinase had little effect on alkaline stability but obviously decreased collagenase activity, developing its potential application in leather treatment. The variants V380, V370, and V355 were thermophilic, with a 1.7-fold enhancement of keratinlytic activity at 60 °C when compared to the wild type. The entire truncation of PPC domain obtained the variant V355 with improved tolerance to alkalinity, salt, chaotropic agents, and detergents. The V355 variant showed more than a 40% improvement in activity under 15% (w/v) NaCl or 4% (w/v) SDS solution, showing excellent stability under harsh washing and unhairing conditions. Our work investigated how protein engineering affects the function of PPC domain of KerSMD.

  16. Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Yannic C. Bartsch

    2018-06-01

    Full Text Available Pro- and anti-inflammatory effector functions of IgG antibodies (Abs depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0 IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors, administered in high doses (2 g/kg to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

  17. SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Mario Saare

    2015-01-01

    Full Text Available The SP100 family members comprise a set of closely related genes on chromosome 2q37.1. The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of SP140L gene through rearrangements of the two neighboring genes, SP100 and SP140, during the evolution of higher primates. The SP140L expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. In conclusion, our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients.

  18. Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis.

    Science.gov (United States)

    Liu, Ying; Tan, Huiling; Tian, Hui; Liang, Chunyang; Chen, She; Liu, Qinghua

    2011-11-04

    The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses the Needs of the Higher Ed Community

    Science.gov (United States)

    Manning, James; Meinke, Bonnie K.; Schultz, Gregory R.; Smith, Denise A.; Lawton, Brandon L.; Gurton, Suzanne; NASA Astrophysics E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of NASA Science Mission Directorate (SMD) Astrophysics EPO projects and their teams to bring cutting-edge discoveries of NASA missions to the introductory astronomy college classroom. The Astrophysics Forum assists scientist and educator involvement in SMD E/PO (uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise) and makes SMD E/PO resources and expertise accessible to the science and education communities. We present three new opportunities for college instructors to bring the latest NASA discoveries in Astrophysics into their classrooms.To address the expressed needs of the higher education community, the Astrophysics Forum collaborated with the Astrophysics E/PO community, researchers, and Astronomy 101 instructors to place individual science discoveries and learning resources into context for higher education audiences. Among these resources are two Resource Guides on the topics of cosmology and exoplanets, each including a variety of accessible sources.The Astrophysics Forum also coordinates the development of the Astro 101 slide set series--5 to 7-slide presentations on new discoveries from NASA Astrophysics missions relevant to topics in introductory astronomy courses. These sets enable Astronomy 101 instructors to include new discoveries not yet in their textbooks into the broader context of the course: http://www.astrosociety.org/education/astronomy-resource-guides/.The Astrophysics Forum also coordinated the development of 12 monthly Universe Discovery Guides, each featuring a theme and a representative object well-placed for viewing, with an accompanying interpretive story, strategies for conveying the topics, and supporting NASA-approved education activities and background information from a spectrum of NASA missions and programs: http://nightsky.jpl.nasa.gov/news-display.cfm?News_ID=611

  20. A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (hGAD65

    Directory of Open Access Journals (Sweden)

    Maxwell Denis

    2008-11-01

    Full Text Available Abstract Background Human glutamic acid decarboxylase 65 (hGAD65 is a key autoantigen in type 1 diabetes, having much potential as an important marker for the prediction and diagnosis of type 1 diabetes, and for the development of novel antigen-specific therapies for the treatment of type 1 diabetes. However, recombinant production of hGAD65 using conventional bacterial or mammalian cell culture-based expression systems or nuclear transformed plants is limited by low yield and low efficiency. Chloroplast transformation of the unicellular eukaryotic alga Chlamydomonas reinhardtii may offer a potential solution. Results A DNA cassette encoding full-length hGAD65, under the control of the C. reinhardtii chloroplast rbcL promoter and 5'- and 3'-UTRs, was constructed and introduced into the chloroplast genome of C. reinhardtii by particle bombardment. Integration of hGAD65 DNA into the algal chloroplast genome was confirmed by PCR. Transcriptional expression of hGAD65 was demonstrated by RT-PCR. Immunoblotting verified the expression and accumulation of the recombinant protein. The antigenicity of algal-derived hGAD65 was demonstrated with its immunoreactivity to diabetic sera by ELISA and by its ability to induce proliferation of spleen cells from NOD mice. Recombinant hGAD65 accumulated in transgenic algae, accounts for approximately 0.25–0.3% of its total soluble protein. Conclusion Our results demonstrate the potential value of C. reinhardtii chloroplasts as a novel platform for rapid mass production of immunologically active hGAD65. This demonstration opens the future possibility for using algal chloroplasts as novel bioreactors for the production of many other biologically active mammalian therapeutic proteins.

  1. Application of indirect immunofluorescent test with an improved HEp-2 substrate tranfected with human Ro60/SSA autoantigens

    International Nuclear Information System (INIS)

    Lv Liangjing; Chen Shunle; Gu Yueying; Shen Nan; Bao Chunde; Wang Yuan; Xue Feng; Ye Peng; Yu Chongzhao

    2006-01-01

    To develop an improved substrate for indirect immunofluorescent test (IIF) to detect anti-Ro/SSA autoantibodies, the human 60-kDa Ro/SSA autoantigens (Ro60) cDNAs were obtained from placental cDNA library using PCR and were cloned into the mammalian expression vectorpEGFP-C1. Then the recombinant plasmids were transfected into HEp-2 cells. We con- firmed the overexpression, localization and antigenicity of fusion proteins in transfected cells by means of fluorescence microscopy, immunoblotting and IIF. HEp-2 and HEp-Ro60 was analyzed by IIF using a panel of 10 precipitinpositive anti-Ro human sera simultaneously. Stable expression of Ro60-GFP (green fluorescent protein) fusion proteins maintained ten more generations. And Ro60-GFP kept the antigenicity of Ro and had its own characteristic immunofluorescent pattern in HEp-Ro60 cells. The transfectants dramatically increased the sensitivity of IIF testing (a mean increase of 6.7-fold in endpoint titer, P<0.01). Eight (8/10) positive an- ti-Ro sera showed characteristic immunofluorescent pattern on HEp-Ro60, including two sera which were antinuclear antibodies (ANA) negative on untransfected HEp-2. IIF-ANA in all healthy sera were negative on HEp-Ro60. As a kind of new substrate of IIF, the Ro60 transfectants can be used to detect anti-Ro antibodies. In addition, transfected HEp-2 cells kept the immunofluorescent property of HEp-2 cells in IIF-ANA tests and could be employed as substrate for the routine IIF-ANA detection. The method improved the sensitivity of IIF-ANA. (authors)

  2. Clinical and serologic parallels to APS-I in patients with thymomas, and autoantigen transcripts in their tumors1

    Science.gov (United States)

    Wolff, Anette S. B.; Kärner, Jaanika; Owe, Jone F.; Oftedal, Bergithe E.V.; Gilhus, Nils Erik; Erichsen, Martina M.; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S.

    2014-01-01

    Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC) plus autoantibodies neutralizing IL-17, IL-22 and type I interferons. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG and/or thymoma for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including CMC, AI and asplenia, respectively in 49/121 (40%) and 10/121 (8%) thymoma patients, but clinical features seldom co-occurred with the corresponding autoantibodies. Both were rare in other MG subgroups (N=126). In 38 APS-I patients, by contrast, we observed neither autoantibodies against muscle antigens nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected under-expression in thymomas, levels were increased for 4 of the 5 TSAgs most frequently targeted by these patients’ autoAbs. Hence the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and HP. PMID:25230752

  3. Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors.

    Science.gov (United States)

    Wolff, Anette S B; Kärner, Jaanika; Owe, Jone F; Oftedal, Bergithe E V; Gilhus, Nils Erik; Erichsen, Martina M; Kämpe, Olle; Meager, Anthony; Peterson, Pärt; Kisand, Kai; Willcox, Nick; Husebye, Eystein S

    2014-10-15

    Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism, and chronic mucocutaneous candidiasis plus autoantibodies neutralizing IL-17, IL-22, and type I IFNs. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG, thymoma, or both for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and we assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including chronic mucocutaneous candidiasis, AI, and asplenia, respectively, in 49 of 121 (40%) and 10 of 121 (8%) thymoma patients, but clinical features seldom occurred together with the corresponding autoantibodies. Both were rare in other MG subgroups (n = 126). In 38 patients with APS-I, by contrast, we observed neither autoantibodies against muscle Ags nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected underexpression in thymomas, levels were increased for four of the five TSAgs most frequently targeted by these patients' autoantibodies. Therefore, the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and hypoparathyroidism. Copyright © 2014 by The American Association of Immunologists, Inc.

  4. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

    Directory of Open Access Journals (Sweden)

    Hassan Mziaut

    2016-08-01

    Full Text Available Objective: Insulin release from pancreatic islet β cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512 (also known as islet antigen 2/Ptprn. Here we investigated how Ica512 modulates SG trafficking and exocytosis. Methods: Transcriptomic changes in Ica512−/− mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. Results: The F-actin modifier villin was consistently downregulated in Ica512−/− mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of β cells and dispersed villin−/− islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. Keywords: F-actin, Granules, Ica512, Insulin, Secretion, Villin

  5. Structural Basis for Recognition and Sequestration of UUUOH 3 ' Temini of Nascent RNA Polymerase III Transcripts by La, a Rheumatic Disease Autoantigen

    Energy Technology Data Exchange (ETDEWEB)

    Teplova,M.; Yuan, Y.; Phan, A.; Malinina, L.; Ilin, S.; Teplov, A.; Patel, D.

    2006-01-01

    The nuclear phosphoprotein La was identified as an autoantigen in patients with systemic lupus erythematosus and Sjogren's syndrome. La binds to and protects the UUUOH 3' terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 Angstroms crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to r(U1-G2-C3-U4-G5-U6-U7-U8-U9OH). The U7-U8-U9OH 3' end, in a splayed-apart orientation, is sequestered within a basic and aromatic amino acid-lined cleft between the La and RRM1 motifs. The specificity-determining U8 residue bridges both motifs, in part through unprecedented targeting of the {beta} sheet edge, rather than the anticipated face, of the RRM1 motif. Our structural observations, supported by mutation studies of both La and RNA components, illustrate the principles behind RNA sequestration by a rheumatic disease autoantigen, whereby the UUUOH 3' ends of nascent RNA transcripts are protected during downstream processing and maturation events.

  6. Peripheral blood mononuclear cells of patients with latent autoimmune diabetes secrete higher levels of pro- & anti-inflammatory cytokines compared to those with type-1 diabetes mellitus following in vitro stimulation with β-cell autoantigens

    Directory of Open Access Journals (Sweden)

    Darshan Badal

    2017-01-01

    Interpretation & conclusions: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.

  7. Regulatory function of a novel population of mouse autoantigen-specific Foxp3 regulatory T cells depends on IFN-gamma, NO, and contact with target cells.

    Directory of Open Access Journals (Sweden)

    Cyndi Chen

    Full Text Available BACKGROUND: Both naturally arising Foxp3(+ and antigen-induced Foxp3(- regulatory T cells (Treg play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel class II MHC tetramer, we have isolated a population of CD4(+ Foxp3(- T cells specific for the autoantigen glutamic acid decarboxylase p286-300 peptide (NR286 T cells from diabetes-resistant non-obese resistant (NOR mice. These Foxp3(- NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-gamma was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg. CONCLUSIONS/SIGNIFICANCE: These studies identified a unique population of autoantigen-specific Foxp3(- Treg that can exert their regulatory function dependent on not only IFN-gamma and NO but also cell contact with target cells.

  8. Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble

    DEFF Research Database (Denmark)

    Christgau, S; Schierbeck, H; Aanstoot, H J

    1991-01-01

    The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic...... acid decarboxylase. We have identified two autoantigenic forms of this protein in rat pancreatic beta-cells, a Mr 65,000 (GAD65) hydrophilic and soluble form of pI 6.9-7.1 and a Mr 64,000 (GAD64) component of pI 6.7. GAD64 is more abundant than GAD65 and has three distinct forms with regard to cellular...

  9. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses the needs of Underrepresented Audiences through NASA Science4Girls and Their Families

    Science.gov (United States)

    Meinke, Bonnie K.; Smith, Denise A.; Bleacher, Lora; Hauck, Karin; Soeffing, Cassie; NASA SMD E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of individual NASA Science Mission Directorate (SMD) Astrophysics EPO projects and their teams to bring the NASA science education resources and expertise to libraries nationwide. The Astrophysics Forum assists scientists and educators with becoming involved in SMD E/PO (which is uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise) and makes SMD E/PO resources and expertise accessible to the science and education communities. The NASA Science4Girls and Their Families initiative partners NASA science education programs with public libraries to provide NASA-themed hands-on education activities for girls and their families. As such, the initiative engages girls in all four NASA science discipline areas (Astrophysics, Earth Science, Planetary Science, and Heliophysics), which enables audiences to experience the full range of NASA science topics and the different career skills each requires. The events focus on engaging this particular underserved and underrepresented audience in Science, Technology, Engineering, and Mathematics (STEM) via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences.

  10. Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies.

    Science.gov (United States)

    Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

    2017-08-01

    Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH 2 -CH=CH-CH 2 -) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than ~1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

  11. A Big Data Task Force Review of Advances in Data Access and Discovery Within the Science Disciplines of the NASA Science Mission Directorate (SMD)

    Science.gov (United States)

    Walker, R. J.; Beebe, R. F.

    2017-12-01

    One of the basic problems the NASA Science Mission Directorate (SMD) faces when dealing with preservation of scientific data is the variety of the data. This stems from the fact that NASA's involvement in the sciences spans a broad range of disciplines across the Science Mission Directorate: Astrophysics, Earth Sciences, Heliophysics and Planetary Science. As the ability of some missions to produce large data volumes has accelerated, the range of problems associated with providing adequate access to the data has demanded diverse approaches for data access. Although mission types, complexity and duration vary across the disciplines, the data can be characterized by four characteristics: velocity, veracity, volume, and variety. The rate of arrival of the data (velocity) must be addressed at the individual mission level, validation and documentation of the data (veracity), data volume and the wide variety of data products present huge challenges as the science disciplines strive to provide transparent access to their available data. Astrophysics, supports an integrated system of data archives based on frequencies covered (UV, visible, IR, etc.) or subject areas (extrasolar planets, extra galactic, etc.) and is accessed through the Astrophysics Data Center (https://science.nasa.gov/astrophysics/astrophysics-data-centers/). Earth Science supports the Earth Observing System (https://earthdata.nasa.gov/) that manages the earth science satellite data. The discipline supports 12 Distributed Active Archive Centers. Heliophysics provides the Space Physics Data Facility (https://spdf.gsfc.nasa.gov/) that supports the heliophysics community and Solar Data Analysis Center (https://umbra.nascom.nasa.gov/index.html) that allows access to the solar data. The Planetary Data System (https://pds.nasa.gov) is the main archive for planetary science data. It consists of science discipline nodes (Atmospheres, Geosciences, Cartography and Imaging Sciences, Planetary Plasma Interactions

  12. Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies

    Science.gov (United States)

    Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

    2017-08-01

    Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than 1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

  13. The orthologue of Sjögren's syndrome nuclear autoantigen 1 (SSNA1 in Trypanosoma brucei is an immunogenic self-assembling molecule.

    Directory of Open Access Journals (Sweden)

    Helen P Price

    Full Text Available Primary Sjögren's Syndrome (PSS is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14 is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13 and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.

  14. Tools You Can Use! E/PO Resources for Scientists and Faculty to Use and Contribute To: EarthSpace and the NASA SMD Scientist Speaker’s Bureau

    Science.gov (United States)

    Buxner, Sanlyn; Shupla, C.; CoBabe-Ammann, E.; Dalton, H.; Shipp, S.

    2013-10-01

    The Planetary Science Education and Public Outreach (E/PO) Forum has helped to create two tools that are designed to help scientists and higher-education science faculty make stronger connections with their audiences: EarthSpace, an education clearinghouse for the undergraduate classroom; and NASA SMD Scientist Speaker’s Bureau, an online portal to help bring science - and scientists - to the public. Are you looking for Earth and space science higher education resources and materials? Come explore EarthSpace, a searchable database of undergraduate classroom materials for faculty teaching Earth and space sciences at both the introductory and upper division levels! In addition to classroom materials, EarthSpace provides news and information about educational research, best practices, and funding opportunities. All materials submitted to EarthSpace are peer reviewed, ensuring that the quality of the EarthSpace materials is high and also providing important feedback to authors. Your submission is a reviewed publication! Learn more, search for resources, join the listserv, sign up to review materials, and submit your own at http://www.lpi.usra.edu/earthspace. Join the new NASA SMD Scientist Speaker’s Bureau, an online portal to connect scientists interested in getting involved in E/PO projects (e.g., giving public talks, classroom visits, and virtual connections) with audiences! The Scientist Speaker’s Bureau helps educators and institutions connect with NASA scientists who are interested in giving presentations, based upon the topic, logistics, and audience. The information input into the database will be used to help match scientists (you!) with the requests being placed by educators. All Earth and space scientists funded by NASA - and/or engaged in active research using NASA’s science - are invited to become part of the Scientist Speaker’s Bureau. Submit your information into the short form at http://www.lpi.usra.edu/education/speaker.

  15. Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sjögren’s Syndrome

    Science.gov (United States)

    Gourzi, V C; Kapsogeorgou, E K; Kyriakidis, N C; Tzioufas, A G

    2015-01-01

    The elevated tissue expression of Ro/SSA and La/SSB autoantigens appears to be crucial for the generation and perpetuation of autoimmune humoral responses against these autoantigens in Sjögren’s syndrome (SS). The mechanisms that govern their expression are not known. miRNAs, the post-transcriptional regulators of gene expression, might be implicated. We have identified previously the miRNAs let7b, miR16, miR181a, miR200b-3p, miR200b-5p, miR223 and miR483-5p that are predicted to target Ro/SSA [Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2)] and La/SSB mRNAs. To study possible associations with autoantigen mRNA expression and disease features, their expression was investigated in minor salivary gland (MSG) tissues, peripheral blood mononuclear cells (PBMC) and long-term cultured non-neoplastic salivary gland epithelial cells (SGEC) from 29 SS patients (20 of 29 positive for autoantibodies to Ro/SSA and La/SSB) and 24 sicca-complaining controls. The levels of miR16 were up-regulated in MSGs, miR200b-3p in SGECs and miR223 and miR483-5p in PBMCs of SS patients compared to sicca-complaining controls. The MSG levels of let7b, miR16, miR181a, miR223 and miR483-5p were correlated positively with Ro52/TRIM21-mRNA. miR181a and miR200b-3p were correlated negatively with Ro52/TRIM21 and Ro60/TROVE2 mRNAs in SGECs, respectively, whereas let7b, miR200b-5p and miR223 associated with La/SSB-mRNA. In PBMCs, let7b, miR16, miR181a and miR483-5p were correlated with Ro52/TRIM21, whereas let7b, miR16 and miR181a were also associated with La/SSB-mRNA expression. Significantly lower miR200b-5p levels were expressed in SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma compared to those without. Our findings indicate that miR16, miR200b-3p, miR223 and miR483-5p are deregulated in SS, but the exact role of this deregulation in disease pathogenesis and autoantigen expression needs to be elucidated. PMID:26201309

  16. New developments in lupus-associated antiphospholipid syndrome

    NARCIS (Netherlands)

    Lockshin, M. D.; Derksen, R. H. W. M.

    2008-01-01

    Systemic lupus erythematosus is the disease in which the antiphospholipid syndrome was first described more than 20 years ago and which is the most frequent underlying disorder in secondary antiphospholipid syndrome. With respect to pathogenic concepts and treatment, the subjects of this review, no

  17. Ida-1, the Caenorhabditis elegans orthologue of mammalian diabetes autoantigen IA-2, potentially acts as a common modulator between Parkinson's disease and Diabetes: role of Daf-2/Daf-16 insulin like signalling pathway.

    Science.gov (United States)

    Fatima, Soobiya; Haque, Rizwanul; Jadiya, Pooja; Shamsuzzama; Kumar, Lalit; Nazir, Aamir

    2014-01-01

    The lack of cure to age associated Parkinson's disease (PD) has been challenging the efforts of researchers as well as health care providers. Recent evidences suggest that diabetic patients tend to show a higher future risk for PD advocating a strong correlation between PD and Diabetes, thus making it intriguing to decipher common genetic cues behind these ailments. We carried out studies on ida-1, the C. elegans orthologue of mammalian type-1 diabetes auto-antigen IA-2 towards achieving its functional workup vis-à-vis various associated endpoints of PD and Diabetes. Employing transgenic C. elegans strain expressing "human" alpha synuclein (NL5901) under normal and increased glucose concentrations, we studied aggregation of alpha synuclein, content of dopamine, expression of dopamine transporter, content of reactive oxygen species, locomotor activity, nuclear translocation of FOXO transcription factor Daf-16, and quantification of Daf2/Daf-16 mRNA. Our findings indicate that ida-1 affords protection in the studied disease conditions as absence of ida-1 resulted in higher alpha-synuclein aggregation under conditions that mimic the blood glucose levels of diabetic patients. We also observed reduced dopamine content, decreased motility, defective Daf-16 translocation and reduced expression of Daf-2 and Daf-16. Our studies establish important function of ida-1 as a modulator in Daf-2/Daf-16 insulin like signalling pathway thus possibly being a common link between PD and Diabetes.

  18. Content of Diabetes-Associated Autoantibodies against Islet Autoantigens (IA-2A, GADA, IAA and the Level of Different Cytokines in Children and Adolescents on the Pre-Clinical and Early Clinical Stages of Type 1 Diabetes Mellitus Development

    Directory of Open Access Journals (Sweden)

    V.V. Popova

    2015-03-01

    Full Text Available The article provides the data on the immunological mechanisms of type 1 diabetes mellitus (T1DM on the preclinical and early clinical stages of disease formation on the basis of studying the features of T1DM pathogenesis, monitoring the process of autoimmune destruction of insulin-producing β-cells by determining the content of diabetes-associated auto-antibodies (the incidence and titers dynamics, the study of the characteristics of cytokine secretion on the pre-clinical stage of T1DM development in children and adolescents. Introduction of new approaches to pre-clinical diagnosis of T1DM allowed determine the group of marker-positive children with burdened heredity and predictable risk of disease development. The study involved 450 healthy normoglycemic children and adolescents aged from 7 to 15 years old. It was revealed that 94 (26.7 % of 366 children with burdened hereditary by at least two-fold determination of DAAb had an increased DAAb titer, mainly GADA and IA-2A, the clinical debut of T1DM manifested in 49 (52.1 % of them from 6 months to 12 years (30.9 ± 3.2 months. T1DM developed in the same period in a child, that was 0.8 % of the 272 (73.3 % DAAb-negative children. There was determined a formula of combined incidence and values of simultaneously elevated DAAb titers to islet autoantigens, namely IA-2A + GADA, which are predictor of the duration of T1DM pre-clinical stage and debut occurrence. It has been also established a disturbance of cytokine production (increased level of pro-inflammatory cytokines IL-1α, IL-6 and FNO-α, IL-8 and IL-16 while reduced concentration of IL-4 in blood plasma as a key factor in the T1DM pathogenesis that causes the debut occurrence, and aggressiveness of its course.

  19. Novel autoantigens immunogenic in COPD patients

    Directory of Open Access Journals (Sweden)

    Stephan Bernhard

    2009-03-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.

  20. Developmental coxa vara associated with spondylometaphyseal dysplasia (DCV/SMD): ''SMD-Corner Fracture Type'' (DCV/SMD-CF) demonstrated in most reported cases

    International Nuclear Information System (INIS)

    Currarino, G.; Birch, J.G.; Herring, J.A.

    2000-01-01

    Background. This paper reports three children with short stature: developmental coxa vara unilateral in the first case and bilateral in the other two; somewhat squared and ''ovoid'' vertebral bodies in the first patient, and normal to slightly tall vertebral bodies in the third; metaphyseal changes in some long tubular bones including bone fragments similar to the corner fractures seen in child abuse in all three patients. Materials and methods. The first and second patients were sisters; their mother, also quite short, had surgical procedures in early life for bilateral ''coxa vara''; their brother, also of short stature, had bilateral coxa valga with otherwise normal femoral heads and necks, and mild metaphyseal changes associated with two minute ''corner fractures'' in the proximal metaphysis of the left tibia. Results. A review of reported cases of developmental coxa vara associated with spondylometaphyseal dysplasia revealed that simulated corner fractures were present in most instances. (orig.)

  1. Search for local parity violation with STAR ZDC-SMD

    Energy Technology Data Exchange (ETDEWEB)

    Wang Gang, E-mail: gwang@physics.ucla.ed [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States)

    2010-06-01

    Parity-odd domains are predicted to lead to charge separation of quarks along the orbital momentum of the system created in non-central relativistic heavy ion collisions. A signal consistent with several of the theoretical expectations has been detected by STAR, with a three particle azimuthal correlator which is a P-even observable, but still sensitive to the charge separation effect. In this correlator, the first two particles are used to reveal the physics of interest, and the third particle serves as a reference for the reaction plane. In this work, to minimize the non-parity correlation between the third particle and the first two, we utilize the spectator neutrons detected by STAR ZDC-SMDs to define the event plane. The 1st-order event plane thus obtained can also be used to study the global strong parity violation effect, and to provide further systematic checks for this analysis. We report measurements of both P-even and P-odd observables using the STAR ZDC-SMDs in Au+Au at 200 GeV. The results are presented as a function of collision centrality, particle separation in rapidity and transverse momentum (p{sub T}). Systematic checks on the impact from the directed flow will also be discussed.

  2. Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

    Science.gov (United States)

    Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

    2013-11-01

    Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE. Copyright © 2013 by the American College of Rheumatology.

  3. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not

  4. Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    Full Text Available To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment.Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants.We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4-targeted ionizing radiation induces additional cycles of tumor cell death, which further augments DAB4 binding to produce a tumor-lethal 'genotoxic chain reaction'. Clinically, this approach may be useful as consolidation treatment after a drug-induced cell death among (small-volume metastatic deposits, the commonest cause of cancer death. This article is part II of a two-part series providing proof-of-concept for the diagnostic and therapeutic use of the DAB4 clone of the La-specific monoclonal antibody, APOMAB.

  5. Developmental coxa vara associated with spondylometaphyseal dysplasia (DCV/SMD): ''SMD-Corner Fracture Type'' (DCV/SMD-CF) demonstrated in most reported cases

    Energy Technology Data Exchange (ETDEWEB)

    Currarino, G. [Texas Univ., Dallas, TX (United States). Dept. of Radiology; Department of Radiology, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219 (United States); Birch, J.G.; Herring, J.A. [Department of Orthopedic Surgery, Texas Scottish Rite Hospital for Children, Dallas, TX (United States)

    2000-01-01

    Background. This paper reports three children with short stature: developmental coxa vara unilateral in the first case and bilateral in the other two; somewhat squared and ''ovoid'' vertebral bodies in the first patient, and normal to slightly tall vertebral bodies in the third; metaphyseal changes in some long tubular bones including bone fragments similar to the corner fractures seen in child abuse in all three patients. Materials and methods. The first and second patients were sisters; their mother, also quite short, had surgical procedures in early life for bilateral ''coxa vara''; their brother, also of short stature, had bilateral coxa valga with otherwise normal femoral heads and necks, and mild metaphyseal changes associated with two minute ''corner fractures'' in the proximal metaphysis of the left tibia. Results. A review of reported cases of developmental coxa vara associated with spondylometaphyseal dysplasia revealed that simulated corner fractures were present in most instances. (orig.)

  6. Immunochemical and autoantigenic properties of the globular domain of basement membrane collagen (type IV).

    Science.gov (United States)

    von der Mark, H; Oberbäumer, I; Timpl, R; Kemler, R; Wick, G

    1985-02-01

    Polyclonal rabbit antibodies raised against the globular domain NC1 of collagen IV from human placenta and a mouse tumor react with conformational antigenic determinants present on the NC1 hexamers and also with the three major subunits obtained after dissociation. The antibodies recognized unique structures within basement membranes and showed a broad tissue reactivity but only limited species cross-reactivity. Using these antibodies, it was possible to detect small amounts of collagen IV antigens from cell cultures and in serum. Monoclonal rat antibodies against mouse NC1 revealed a similar reaction potential. Autoantibodies could be produced in mice against mouse NC1 which react with kidney and lung basement membranes in a pathological manner, mimicking Goodpasture syndrome.

  7. Heterogeneous nuclear ribonucleoproteins C1/C2 identified as autoantigens by biochemical and mass spectrometric methods

    DEFF Research Database (Denmark)

    Heegaard, N H; Larsen, Martin Røssel; Muncrief, T

    2000-01-01

    ribonucleoproteins. The clinical spectrum of patients with these autoantibodies includes arthritis, psoriasis, myositis, and scleroderma. None of 59 patients with rheumatoid arthritis, 19 with polymyositis, 33 with scleroderma, and 10 with psoriatic arthritis had similar antibodies. High-resolution protein...

  8. Glutamate decarboxylase-derived IDDM autoantigens displayed on self-assembled protein nanoparticles

    International Nuclear Information System (INIS)

    Choi, Hyoung; Ahn, Ji-Young; Sim, Sang Jun; Lee, Jeewon

    2005-01-01

    The recombinant ferritin heavy chain (FTN-H) formed self-assembled spherical nanoparticles with the size comparable to native one. We tried to express the GAD65 COOH-terminal fragments, i.e., 448-585 (GAD65 448-585 ), 487-585 (GAD65 487-585 ), and 512-585 (GAD65 512-585 ) amino acid fragments, using FTN-H as N-terminus fusion expression partner in Escherichia coli. All of recombinant fusion proteins (FTN-H::GAD65 448-585 , FTN-H::GAD65 487-585 , and FTN-H::GAD65 512-585 ) also formed spherical nanoparticles due probably to the self-assembly function of the fused ferritin heavy chain. The antigenic epitopes within GAD65 448-585 , GAD65 487-585 , and GAD65 512-585 against insulin-dependent diabetes mellitus (IDDM) marker (autoantibodies against GAD65) were localized at the surface of the spherical protein nanoparticles so that anti-GAD65 Ab could recognize them. Protein nanoparticles like FTN-H seem to provide distinct advantages over other inorganic nanoparticles (e.g., Au, Ag, CdSe, etc.) in that through the bacterial synthesis, the active capture probes can be located at the nanoparticle surface with constant orientation/conformation via covalent cross-linking without complex chemistry. Also it is possible for the protein nanoparticles to have uniform particle size, which is rarely achieved in the chemical synthesis of inorganic nanoparticles. Thus, the recombinant ferritin particles can be used as a three-dimensional (spherical) and nanometer-scale probe structure that is a key component in ultra-sensitive protein chip for detecting protein-small molecule interactions and protein-protein interactions

  9. Antibodies to autoantigen targets in myasthenia and their value in clinical practice

    Directory of Open Access Journals (Sweden)

    S. I. Dedaev

    2014-01-01

    Full Text Available Myasthenia gravis is a classic autoimmune disease, which clinical manifestations in the form of weakness and abnormal muscle fatigue, due to the damaging effect of polyclonal antibodies to different structures of the neuromuscular synapse and muscles. The study of autoimmune substrate with myasthenia is routine in many clinics dealing with the problems of neuromuscular pathology, and the identification of high concentration of serum antibodies to a number of antigenic structures is the gold standard in diagnosis.Determination of serum antibodies to various autoimmune targets is an important tool in clinical practice. The majority of patients shows the high concentration of antibodies to AchR that gives the opportunity to use it as an important diagnostic criterion. The specificity of changes in the concentration of AchR-antibodies due to pathogenetic treatment allows to objectify the suppression of autoimmune aggression and evaluate the reliability of remission. However, the absence of AchR-antibodies when there are clear clinical and electromyography signs of myasthenia gravis suggests an autoimmune attack against a number of other targets, the most studied of which is the MuSK. On the contrary, patients with myasthenia gravis associated with thymoma, almost always have a higher level of AchR-antibodies. The presence of thymoma is accompanied by the generation of antibodies to titin and RyR, which is also observed in persons with late-onset myasthenia without thymoma. High concentration of antibodies to these structures can be interpreted as a reliable sign of thymoma in patients younger than 60 years.

  10. Catalase and alpha-enolase : two novel granulocyte autoantigens in inflammatory bowel disease (IBD)

    NARCIS (Netherlands)

    Roozendaal, C; Zhao, MH; Horst, G; Lockwood, CM; Kleibeuker, JH; Limburg, PC; Nelis, GF; Kallenberg, CGM

    1998-01-01

    In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in

  11. Catalase and alpha-enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD)

    NARCIS (Netherlands)

    Roozendaal, C.; Zhao, M.H.; Lockwood, C.M.; Kleibeuker, Jan; Limburg, Piet; Nelis, G.F.; Kallenberg, Cees; Horst, G.

    1998-01-01

    In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in

  12. Identification, characterization and application of autoantigens in type 1 diabetes mellitus

    NARCIS (Netherlands)

    H-J. Aanstoot (Henk-Jan)

    1993-01-01

    textabstractType 1 diabetes mellitus or insulin dependent diabetes mellitus is a disease characterized by the selective destruction of insulin producing B-cells in the islets of Langerhans. The exact cause of this destruction is unknown, but is mediated by cells of the immune system. The immune

  13. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for autoimmune diseases.

  14. Critical review of Ames Life Science participation in Spacelab Mission Development Test 3: The SMD 3 management study

    Science.gov (United States)

    Helmreich, R.; Wilhelm, J.; Tanner, T. A.; Sieber, J. E.; Burgenbauch, S.

    1978-01-01

    A management study was conducted to specify activities and problems encountered during the development of procedures for documentation and crew training on experiments, as well as during the design, integration, and delivery of a life sciences experiment payload to Johnson Space Center for a 7 day simulation of a Spacelab mission. Conclusions and recommendations to project management for current and future Ames' life sciences projects are included. Broader issues relevant to the conduct of future scientific missions under the constraints imposed by the environment of space are also addressed.

  15. Silenced B-Cell Receptor Response To Autoantigen In A Poor-Prognostic Subset Of Chronic Lymphocytic Leukemia

    DEFF Research Database (Denmark)

    Bergh, Ann-Charlotte; Evaldsson, Chamilly; Pedersen, Lone Bredo

    2014-01-01

    Chronic lymphocytic leukemia B cells express auto/xeno antigen-reactive antibodies that bind to self-epitopes and resemble natural IgM antibodies in their repertoire. One of the antigenic structures recognized is oxidation-induced malonedialdehyde that is present on low-density lipoprotein......-cell receptor unresponsiveness to cognate self-antigen on its own in poor-prognostic subset #1 chronic lymphocytic leukemia, indicating that these cells proliferate by other mechanisms that may override B-cell receptor silencing brought about in a context of self-tolerance/anergy. These novel findings have...

  16. The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development

    Czech Academy of Sciences Publication Activity Database

    Včeláková, J.; Blatný, R.; Halbhuber, Z.; Kolář, Michal; Neuwirth, Aleš; Petruželková, L.; Ulmannová, T.; Koloušková, S.; Sumnik, Z.; Pithová, P.; Krivjanská, M.; Filipp, Dominik; Štechová, K.

    2013-01-01

    Roč. 2013, May (2013), s. 589451 ISSN 2314-6745 Grant - others:GA MŠk(CZ) 2B06019 Institutional support: RVO:68378050 Keywords : type 1 diabetes * autoimmune disease * Th17 * TGF-beta Subject RIV: EB - Genetics ; Molecular Biology

  17. Analysis of antibody responses against Coxsackie virus B4 protein 2C and the diabetes autoantigen GAD65.

    NARCIS (Netherlands)

    Vreugdenhil, G.R.; Batstra, M.R.; Aanstoot, H.J.; Melchers, W.J.G.; Galama, J.M.D.

    1999-01-01

    Type I diabetes mellitus results from the autoimmune destruction of insulin producing beta cells in the pancreas. Certain viral infections, especially those caused by coxsackie B viruses and related enteroviruses, have been associated with the development of type I diabetes. The sequence homology

  18. Inhibition of STAT3 Signaling Reduces IgA1 Autoantigen Production in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Koshi Yamada

    2017-11-01

    Discussion: Our results revealed that IL-6−induced aberrant activation of STAT3-mediated overproduction of galactose-deficient IgA1. STAT3 signaling pathway may thus represent a new target for disease-specific therapy of IgA nephropathy.

  19. Army Transformation in the Age of Globalization - Implementing Directed Change with Strategic Management Design (SMD): An Analysis Based on the Army Staff in the German Ministry of Defense

    National Research Council Canada - National Science Library

    Schaefer, Christof

    2008-01-01

    ..." and to "learn and adapt" effectively. Moreover, an improved decision process can rally mutual commitment among politicians, military leaders, and the nation's citizens for German Army long-term excellence...

  20. Army Transformation in the Age of Globalization - Implementing Directed Change with Strategic Management Design (SMD): An Analysis Based on the Army Staff in the German Ministry of Defense

    Science.gov (United States)

    2008-05-01

    management. Et.al: Philip Kotler , Marketing Management, (New York: Prentice-Hall, 1991), 701. John R. Hauser, Duncan I. Simester and Birger Wernerfelt...Oldenburg: Carl-von-Ossietzky-Universtät, August 2002. Kotler , Philip. Marketing Management, New York et.al: Prentice-Hall, 1991. Kotter, P. John...paper analyses the macro- and micro organizational peculiarities and opportunities of the German Army. Best practices and key principles from profit

  1. B-CELL EPITOPE ON THE U1 SNRNP-C AUTOANTIGEN CONTAINS A SEQUENCE SIMILAR TO THAT OF THE HERPES-SIMPLEX VIRUS PROTEIN

    NARCIS (Netherlands)

    MISAKI, Y; YAMAMOTO, K; YANAGI, K; MIURA, H; ICHIJO, H; KATO, T; MATO, T; WELLINGWESTER, S; NISHIOKA, K; ITO, K

    The mechanism of autoantibody production in autoimmune diseases is not well understood. In the present study we performed the B cell epitope mapping of the U1 small nuclear ribonucleoprotein (snRNP)-C, one of the target molecules of anti-nRNP autoantibody to investigate how B cells respond to the

  2. The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters the nucleus upon cellular exposure to nitric oxide

    International Nuclear Information System (INIS)

    Espinosa, Alexander; Oke, Vilija; Elfving, Ase; Nyberg, Filippa; Covacu, Ruxandra; Wahren-Herlenius, Marie

    2008-01-01

    Patients with the systemic autoimmune diseases Sjoegrens's syndrome and systemic lupus erythematosus often have autoantibodies against the intracellular protein Ro52. Ro52 is an E3 ligase dependent on the ubiquitin conjugation enzymes UBE2D1 and UBE2E1. While Ro52 and UBE2D1 are cytoplasmic proteins, UBE2E1 is localized to the nucleus. Here, we investigate how domains of human Ro52 regulate its intracellular localization. By expressing fluorescently labeled Ro52 and Ro52 mutants in HeLa cells, an intact coiled-coil domain was found to be necessary for the cytoplasmic localization of Ro52. The amino acids 381-470 of the B30.2 region were essential for translocation into the nucleus. Furthermore, after exposure of HeLa cells to the inflammatory mediator nitric oxide (NO), Ro52 translocated to the nucleus. A nuclear localization of Ro52 in inflamed tissue expressing inducible NO synthetase (iNOS) from cutaneous lupus patients was observed by immunohistochemistry and verified in NO-treated cultures of patient-derived primary keratinocytes. Our results show that the localization of Ro52 is regulated by endogenous sequences, and that nuclear translocation is induced by an inflammatory mediator. This suggests that Ro52 has both cytoplasmic and nuclear substrates, and that Ro52 mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus

  3. Co-purification of arrestin like proteins with alpha-enolase from bovine myocardial tissues and the possible role in heart diseases as an autoantigen

    Energy Technology Data Exchange (ETDEWEB)

    Mirshahi, M., E-mail: massoud.mirshahi@inserm.fr; Le Marchand, S.

    2015-05-08

    Aim: Previously, we reported that visual arrestin co-purified with glycolytic enzymes. The aim of this study was to analyze the co-purification of arrestin like proteins (ALP) in bovine cardiac tissues with enolases. Methods: The soluble extract of bovine myocardial tissues from different regions such as left and right atriums and ventricles of the bovine heart (n = 3) was analyzed by ACA-34 gel filtration, immuno-affinity column, SDS-PAGE, ELISA, western blot and a sandwich immune assay for quantification of ALP and sequence analysis. Results: We observed that; 1) The cardiac muscle contained a 50 kDa ALP at a concentration of 751 pg/mg of soluble protein extract, 2) ALP purified, by immunoaffinity, contained alpha-enolase of 48 kDa confirmed by protein sequence analysis; 3) Cardiomyocyte cells exposed to anti arrestin and anti enolase monoclonal antibodies showed decreased proliferation in vitro, 4) High level of autoantibodies were detected by ELISA (3.57% for arrestin and 9.12% for α-enolase) in serum of patients with infarcted heart disease. Conclusion: We suggest a possible interaction between ALP and alpha-enolases yielding a complex that may be involved in the induction of cardiac autoimmune diseases. - Highlights: • We examine a possible interaction between arrestin like protein and alpha-enolases in cardiomyocyte. • We demonstrated the effect of antibodies against arrestin and enolase on cardiomyocyte cell proliferation. • We suggest that this proteins complex may be involved in the induction of cardiac autoimmune diseases.

  4. Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid.

    Science.gov (United States)

    Banda, Kalyan; Gregg, Christopher J; Chow, Renee; Varki, Nissi M; Varki, Ajit

    2012-08-17

    Although N-acetyl groups are common in nature, N-glycolyl groups are rare. Mammals express two major sialic acids, N-acetylneuraminic acid and N-glycolylneuraminic acid (Neu5Gc). Although humans cannot produce Neu5Gc, it is detected in the epithelial lining of hollow organs, endothelial lining of the vasculature, fetal tissues, and carcinomas. This unexpected expression is hypothesized to result via metabolic incorporation of Neu5Gc from mammalian foods. This accumulation has relevance for diseases associated with such nutrients, via interaction with Neu5Gc-specific antibodies. Little is known about how ingested sialic acids in general and Neu5Gc in particular are metabolized in the gastrointestinal tract. We studied the gastrointestinal and systemic fate of Neu5Gc-containing glycoproteins (Neu5Gc-glycoproteins) or free Neu5Gc in the Neu5Gc-free Cmah(-/-) mouse model. Ingested free Neu5Gc showed rapid absorption into the circulation and urinary excretion. In contrast, ingestion of Neu5Gc-glycoproteins led to Neu5Gc incorporation into the small intestinal wall, appearance in circulation at a steady-state level for several hours, and metabolic incorporation into multiple peripheral tissue glycoproteins and glycolipids, thus conclusively proving that Neu5Gc can be metabolically incorporated from food. Feeding Neu5Gc-glycoproteins but not free Neu5Gc mimics the human condition, causing tissue incorporation into human-like sites in Cmah(-/-) fetal and adult tissues, as well as developing tumors. Thus, glycoproteins containing glycosidically linked Neu5Gc are the likely dietary source for human tissue accumulation, and not the free monosaccharide. This human-like model can be used to elucidate specific mechanisms of Neu5Gc delivery from the gut to tissues, as well as general mechanisms of metabolism of ingested sialic acids.

  5. Mapping of epitopes for autoantibodies to the Type 1 diabetes autoantigen IA-2 by peptide phage display and molecular modelling: Overlap of antibody and T-cell determinants

    DEFF Research Database (Denmark)

    A. Dromey, James; Weenink, Sarah M.; Peters, Günther H.J.

    2004-01-01

    IA-2 is a major target of autoimmunity in type 1 diabetes. IA-2 responsive T cells recognize determinants within regions represented by amino acids 787–817 and 841–869 of the molecule. Epitopes for IA-2 autoantibodies are largely conformational and not well defined. In this study, we used peptide......, and aromatic residues and amino acids contributing to the epitope investigated using site-directed mutagenesis. Mutation of each of amino acids Asn858, Glu836, and Trp799 reduced 96/3 Ab binding by >45%. Mutations of these residues also inhibited binding of serum autoantibodies from IA-2 Ab-positive type 1...... phage display and homology modeling to characterize the epitope of a monoclonal IA-2 Ab (96/3) from a human type 1 diabetic patient. This Ab competes for IA-2 binding with Abs from the majority of patients with type 1 diabetes and therefore binds a region close to common autoantibody epitopes. Alignment...

  6. Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.

    LENUS (Irish Health Repository)

    O'Brien, Eóin C

    2015-01-01

    ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.

  7. Immune response against the coiled coil domain of Sjögren's syndrome associated autoantigen Ro52 induces salivary gland dysfunction.

    Science.gov (United States)

    Sroka, Magdalena; Bagavant, Harini; Biswas, Indranil; Ballard, Abigail; Deshmukh, Umesh S

    2018-01-31

    The structural domains of Ro52, termed the RING, B-box, coiled coil (CC) and B30.2/SPRY are targets of anti-Ro52 in multiple autoimmune disorders. In Sjögren's syndrome patients, the presence of anti-Ro52 is associated with higher disease severity, and in mice, they induce salivary gland hypofunction. This study was undertaken to investigate whether immune responses against different domains of Ro52, influences salivary gland disease in mice. Female NZM2758 mice were immunised with Ro52 domains expressed as recombinant fusion proteins with maltose binding protein (MBP) [MBP-RING-B-box, MBP-CC, MBP-CC(ΔC19), MBP-B30.2/SPRY]. Sera from immunised mice were studied for IgG antibodies to Ro52 by immunoprecipitation, and to salivary gland cells by immunofluorescence. Pilocarpine-induced saliva production was measured to evaluate salivary gland function. Submandibular glands were investigated by histopathology for inflammation and by immune-histochemistry for IgG deposition. Mice immunised with different Ro52-domains had comparable reactivity to Ro52 and to salivary gland cells. However, only mice immunised with the CC domain and its C-terminal truncated version CC(ΔC19) showed a significant drop in saliva production. None of the mice developed severe salivary gland inflammation. The salivary gland hypofunction significantly correlated with increased intra-lobar IgG deposits in the submandibular salivary glands. Our data demonstrate that epitope specificity of anti-Ro52 antibodies plays a critical role in the induction of glandular dysfunction. Clearly, screening Sjögren's syndrome patients for relative levels of Ro52 domain specific antibodies will be more informative for associating anti-Ro52 with clinical measures of the disorder.

  8. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

    Science.gov (United States)

    Hacohen, Yael; Wright, Sukhvir; Waters, Patrick; Agrawal, Shakti; Carr, Lucinda; Cross, Helen; De Sousa, Carlos; DeVile, Catherine; Fallon, Penny; Gupta, Rajat; Hedderly, Tammy; Hughes, Elaine; Kerr, Tim; Lascelles, Karine; Lin, Jean-Pierre; Philip, Sunny; Pohl, Keith; Prabahkar, Prab; Smith, Martin; Williams, Ruth; Clarke, Antonia; Hemingway, Cheryl; Wassmer, Evangeline; Vincent, Angela; Lim, Ming J

    2013-01-01

    Objective To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens. Method Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. Results Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect. Conclusions Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future. PMID:23175854

  9. In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen.

    Science.gov (United States)

    Al-Ejeh, Fares; Darby, Jocelyn M; Pensa, Katherine; Diener, Kerrilyn R; Hayball, John D; Brown, Michael P

    2007-09-15

    To investigate the potential of the La-specific monoclonal antibody (mAb) 3B9 as an in vivo tumor-targeting agent. The murine EL4 lymphoma cell line was used for in vitro studies and the EL4 model in which apoptosis was induced with cyclophosphamide and etoposide was used for in vivo studies. In vitro studies compared 3B9 binding in the EL4 cell with that in its counterpart primary cell type of the thymocyte. For in vivo studies, 3B9 was intrinsically or extrinsically labeled with carbon-14 or 1,4,7,10-tetra-azacylododecane-N,N',N'',N''''-tetraacetic acid-indium-111, respectively, and biodistribution of the radiotracers was investigated in EL4 tumor-bearing mice, which were treated or not with chemotherapy. La-specific 3B9 mAb bound EL4 cells rather than thymocytes, and binding was detergent resistant. 3B9 binding to dead EL4 cells in vitro was specific, rapid, and saturable. Significantly, more 3B9 bound dead EL4 tumor explant cells after host mice were treated with chemotherapy, which suggested that DNA damage induced 3B9 binding. Tumor binding of 3B9 in vivo was antigen specific and increased significantly after chemotherapy. Tumor accumulation of 3B9 peaked at approximately 50% of the injected dose per gram of tumor 72 h after chemotherapy and correlated with increased tumor cell death. Tumor/organ ratios of 3B9 biodistribution, which included the tumor/blood ratio, exceeded unity 48 or more hours after chemotherapy. La-specific mAb selectively targeted dead tumor cells in vivo, and targeting was augmented by cytotoxic chemotherapy. This novel cell death radioligand may be useful both for radioimmunoscintigraphy and radioimmunotherapy.

  10. Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome

    International Nuclear Information System (INIS)

    Mimori, Tsuneyo; Ohosone, Yasuo; Hama, Nobuaki; Suwa, Akira; Akizuki, Masashi; Homma, Mitsuo; Griffith, A.J.; Hardin, J.A.

    1990-01-01

    Anti-Ku (p70/p80) autoantibodies in patients with scleroderma-polymyositis overlap syndrome recognize a 70-kDa/80-kDa protein heterodimer which binds to terminal regions of double-stranded DNA. In the present study, the authors isolated full-length cDNAs that encode the 80-kDa Ku subunit. Initial screening of a human spleen cDNA library with anti-Ku antibodies yielded a cDNA of 1.0 kilobase (kb) (termed K71) encoding a portion of the 80-kDa Ku polypeptide (identification based on immunological criteria). In RNA blots, this cDNA hybridized with two mRNAs of 3.4 and 2.6 kb. In vitro transcription and translation experiments produced an immunoprecipitable polypeptide which comigrated with the 80-kDa Ku subunit. The Ku80-6 cDNA proved to be 3304 nucleotides in length, with an additional poly(A) tail, closely approximating the size of the larger mRNA. It contains a single long open reading frame encoding 732 amino acids. The putative polypeptide has a high content of acidic amino acids and a region with periodic repeat of leucine in every seventh position which may form the leucine zipper structure. In genomic DNA blots, probes derived from the opposite ends of cDNA Ku80-6 hybridized with several nonoverlapping restriction fragments from human leukocyte DNA, indicating that the gene encoding the 80-kDa Ku polypeptide is divided into several exons by intervening sequences

  11. Influence of doping of Mn{sup +2} and Co{sup +2} in ZnO synthesized by combustion reaction for use in DMS; Influencia da dopagem do Mn{sup +2} e Co{sup +2} no ZnO sintetizado por reacao de combustao para uso em SMD

    Energy Technology Data Exchange (ETDEWEB)

    Torquato, R.; Costa, A.C.F.M. [Universidade Federal de Campina Grande (UFCG), Campina Grande, PB (Brazil). Departamento de Engenharia de Materiais; Shirsath, S.E. [Department of Physics, Vivekanand College, Aurangabad, MS (India); Kiminami, R.H.A. [Universidade Federal de Sao Carlos (UFSCar), SP (Brazil). Departamento de Engenharia de Materiais

    2011-07-01

    ZnO is a semiconducting ceramics used for development of electrical devices such as varistors, chemical sensors, piezoelectric transducers and diluted magnetic semiconductors. So this paper proposes to investigate the influence of doping of 0.1 mol of Mn{sup +2} and Co{sup +2} on the structure, morphology and magnetic measurements of ZnO synthesized by combustion reaction in DMS applications. The resulting samples were characterized by XRD, SEM, BET, VSM. The combustion temperature for samples doped with Mn and Co were 512 deg C and 397 °C, respectively. XRD results for both samples showed the formation of ZnO as the major phase, with crystallite size of 21nm and 23nm and a surface area of 59 and 17 m2/g for samples doped with Mn{sup +2} and Co{sup +2}, respectively. The magnetic measurements showed values of saturation magnetization and coercive force of 12 and 3 emu/g, and 94 and 237Oe, respectively. (author)

  12. Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases?

    Science.gov (United States)

    Jansen, Manon A A; Spiering, Rachel; Broere, Femke; van Laar, Jacob M; Isaacs, John D; van Eden, Willem; Hilkens, Catharien M U

    2018-01-01

    Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T-cell response while leaving other, protective, T-cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. A possible solution is to use surrogate autoantigens for loading of tolDCs. We propose that heat-shock proteins may be a relevant surrogate antigen, as they are evolutionarily conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models. In this review, we provide an overview on how immune tolerance may be restored by tolDCs, the problem of selecting relevant autoantigens for loading of tolDCs, and why heat-shock proteins could be used as surrogate autoantigens. © 2017 John Wiley & Sons Ltd.

  13. Arabidopsis CDS blastp result: AK101105 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101105 J033025D11 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediabe...tic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting com

  14. RENAL VASCULITIS IN 2012 Reclassification and the introduction of biologicals

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2012 saw the classification of the systemic vasculitides revised. Genetic studies showed that granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are different diseases with aberrant immune responses to different autoantigens. B-cell depletion with rituximab also acquired a

  15. Characteristics of Prevotella intermedia-specific CD4+ T cell clones from peripheral blood of a chronic adult periodontitis patient

    NARCIS (Netherlands)

    Wassenaar, A.; Reinhardus, C.; Abraham-Inpijn, L.; Snijders, A.; Kievits, F.

    1998-01-01

    Periodontitis is a chronic destructive inflammatory disease associated with periodontopathic bacteria. In addition, autoantigens such as collagen and heat shock proteins (hsp) have been suggested to play a role. Established periodontal lesions are characterized by dense infiltrations of immune cells

  16. Pituitary autoantibodies in endocrine disorders

    OpenAIRE

    Bensing, Sophie

    2005-01-01

    Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid...

  17. Kind of blue

    DEFF Research Database (Denmark)

    Bro, Margrethe Langer; Jespersen, Kira Vibe; Hansen, Julie Bolvig

    2018-01-01

    RCT's (N = 1784) of which 20 were eligible for the meta-analysis (N = 1565). Music reduced anxiety (SMD -0·80 [95% CI, -1.35 to -0.25]), pain (SMD -0.88 [95% CI -1.45 to -0.32]), and improved mood (SMD -0.55 [95% CI, -0.98 to -0.13]). However, studies were hampered by heterogeneity with I(2) varying...

  18. Parasympathetic functions in children with sensory processing disorder

    Directory of Open Access Journals (Sweden)

    Roseann C Schaaf

    2010-03-01

    Full Text Available The overall goal of this study was to determine if Parasympathetic Nervous System Activity (PsNS is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS functioning affects sensory reactivity in children who have a type of condition associated with Sensory Processing Disorders (SPD termed Sensory Modulation Dysfunction (SMD. If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children. The primary aims of this project were to: (1 evaluate PsNS activity in children with SMD compared to typically developing (TYP children, and (2 determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that the children with severe SMD demonstrated a trend for low baseline parasympathetic activity, compared to TYP children, suggesting this may be a biomarker for severe SMD. In addition, children with SMD demonstrated significantly poorer adaptive behavior. These results provide preliminary evidence that children who demonstrate SMD may have physiological responses that are different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child’s ability to engage in everyday social, communication, and daily living skills.

  19. [The role of mitochondrial permeability transition pore in the occurrence of septic myocardial depression].

    Science.gov (United States)

    Jin, Shanzi; Wang, Sheng

    2016-08-01

    Sepsis is defined as life-threatening organ dysfunction caused by a dys-regulated host response to infection and septic myocardial depression (SMD) is a common complication. Pathogenesis of SMD is complicated and there is lack of specific treatment. Mitochondrial damage is an important pathological basis of SMD, and mitochondrial permeability transition pore (MPTP) plays an important role in maintaining the normal structure and function of the mitochondria. The change of MPTP during sepsis is summarized in this review so as to reveal the significant mechanism of MPTP in the occurrence of SMD.

  20. Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

    Science.gov (United States)

    Elgebaly, Ahmed; Elfil, Mohamed; Attia, Attia; Magdy, Mayar; Negida, Ahmed

    2018-02-01

    Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

  1. Prediction of pKa values for druglike molecules using semiempirical quantum chemical methods

    DEFF Research Database (Denmark)

    Jensen, Jan Halborg; Swain, Christopher J; Olsen, Lars

    2017-01-01

    Rapid yet accurate pKa prediction for druglike molecules is a key challenge in computational chemistry. This study uses PM6-DH+/COSMO, PM6/COSMO, PM7/COSMO, PM3/COSMO, AM1/COSMO, PM3/SMD, AM1/SMD, and DFTB3/SMD to predict the pKa values of 53 amine groups in 48 druglike compounds. The approach uses...... uncertainties of ±0.2-0.3 pH units, which make them statistically equivalent. However, for all but PM3/SMD and AM1/SMD the RMSEs are dominated by a single outlier, cefadroxil, caused by proton transfer in the zwitterionic protonation state. If this outlier is removed, the RMSE values for PM3/COSMO and AM1/COSMO...... drop to 1.0 ± 0.2 and 1.1 ± 0.3, whereas PM3/SMD and AM1/SMD remain at 1.5 ± 0.3 and 1.6 ± 0.3/0.4 pH units, making the COSMO-based predictions statistically better than the SMD-based predictions. For pKa calculations where a zwitterionic state is not involved or proton transfer in a zwitterionic state...

  2. Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

    Science.gov (United States)

    Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

    2011-01-01

    Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

  3. Deshpande, Prof. Suresh Madhusudhan

    Indian Academy of Sciences (India)

    ... Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560 064, Karnataka Contact: Office: (080) 2208 2861. Residence: (080) 2341 2029. Mobile: 94484 71243. Fax: (080) 2208 2766. Email: smd@jncasr.ac.in, desh1942@gmail.com. http://www.jncasr.ac.in/smd/ · YouTube · Twitter · Facebook ...

  4. Differentiating Bipolar Disorder--Not Otherwise Specified and Severe Mood Dysregulation

    Science.gov (United States)

    Towbin, Kenneth; Axelson, David; Leibenluft, Ellen; Birmaher, Boris

    2013-01-01

    Objective: Bipolar disorder--not otherwise specified (BP-NOS) and severe mood dysregulation (SMD) are severe mood disorders that were defined to address questions about the diagnosis of bipolar disorder (BD) in youth. SMD and BP-NOS are distinct phenotypes that differ in clinical presentation and longitudinal course. The purpose of this review is…

  5. Neural Correlates of Reversal Learning in Severe Mood Dysregulation and Pediatric Bipolar Disorder

    Science.gov (United States)

    Adleman, Nancy E.; Kayser, Reilly; Dickstein, Daniel; Blair, R. James R.; Pine, Daniel; Leibenluft, Ellen

    2011-01-01

    Objective: Outcome and family history data differentiate children with severe mood dysregulation (SMD), a syndrome characterized by chronic irritability, from children with "classic" episodic bipolar disorder (BD). Nevertheless, the presence of cognitive inflexibility in SMD and BD highlights the need to delineate neurophysiologic similarities and…

  6. Effect of Combination Therapy on Joint Destruction in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, N.; Hubeck-Graudal, T.; Tarp, S.

    2014-01-01

    identified in a search of electronic archives of biomedical literature and included in a star-shaped network meta-analysis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. Effects are reported as standardized mean differences (SMD......). The effects of data from 39 trials published in the period 1989-2012 were as follows: Double DMARD: -0.32 SMD (CI: -0.42, -0.22); triple DMARD: -0.46 SMD (CI: -0.60, -0.31); 1 DMARD plus TNFi: -0.30 SMD (CI: -0.36, -0.25); 1 DMARD plus abatacept: -0.20 SMD (CI: -0.33, -0.07); 1 DMARD plus tocilizumab: -0.......34 SMD (CI: -0.48, -0.20); 1 DMARD plus CD20i: -0.32 SMD (CI: -0.40, -0.24). The indirect comparisons showed similar effects between combination treatments apart from triple DMARD being significantly better than abatacept plus methotrexate (2 0.26 SMD (CI: -0.45, -0.07)) and TNFi plus methotrexate (-0...

  7. Digital Sport Medical Record: Sigh or a blessing?

    NARCIS (Netherlands)

    Stege, J.P.; Fleuren, M.A.H.; van der Knaap, E.T.W.; Stubbe, J.H.

    2013-01-01

    Since 2004, there have been several initiatives regarding the development of a digital Sport Medical Record (SMD). Interviews with the Netherlands Association of Sports Medicine (VSG) show that there are particular problems with commissioning of the digital SMD. During spring 2012, two focus group

  8. Effect of postsurgical rehabilitation programmes in patients operated for lung cancer

    DEFF Research Database (Denmark)

    Sommer, Maja S; Staerkind, Maja E B; Christensen, Jan

    2018-01-01

    and physical component of health-related quality of life in the intervention group (standardized mean difference (SMD) 0.48; 95% confidence interval (CI) 0.04-0.93) compared with the control group (SMD 0.50; 95% CI 0.19-0.82). There was no difference between the effect of late- and early-initiated exercise...

  9. Het digitale sport medisch dossier: zucht of zegen? [Digital Sport Medical Record: Sigh or a blessing?

    NARCIS (Netherlands)

    Stege, J.P.; Fleuren, M.A.H.; Knaap, E.T.W. van der; Stubbe, J.H.

    2013-01-01

    Sinds 2004 zijn er verschillende initiatieven ontplooid rondom de ontwikkeling van een digitaal Sport Medisch Dossier (SMD). Uit gesprekken met de Vereniging voor Sportgeneeskunde (VSG) blijkt dat er vooral problemen worden gesignaleerd met de ingebruikname van het digitale SMD. In het voorjaar van

  10. Attention Deficit Hyperactivity Disorder and Sensory Modulation Disorder: A Comparison of Behavior and Physiology

    Science.gov (United States)

    Miller, Lucy Jane; Nielsen, Darci M.; Schoen, Sarah A.

    2012-01-01

    Children with attention deficit hyperactivity disorder (ADHD) are impulsive, inattentive and hyperactive, while children with sensory modulation disorder (SMD), one subtype of Sensory Processing Disorder, have difficulty responding adaptively to daily sensory experiences. ADHD and SMD are often difficult to distinguish. To differentiate these…

  11. A Novel Group Therapy for Children with ADHD and Severe Mood Dysregulation

    Science.gov (United States)

    Waxmonsky, James G.; Wymbs, Fran A.; Pariseau, Meaghan E.; Belin, Peter J.; Waschbusch, Daniel A.; Babocsai, Lysett; Fabiano, Gregory A.; Akinnusi, Opeolowa O.; Haak, Jenifer L.; Pelham, William E.

    2013-01-01

    Objective: No psychosocial treatments have been developed for children with ADHD and severe mood dysregulation (SMD) despite the significant prevalence and morbidity of this combination. Therefore, the authors developed a novel treatment program for children with ADHD and SMD. Method: The novel therapy program integrates components of…

  12. Does Ramadan fasting alter body weight and blood lipids and fasting blood glucose in a healthy population? A meta-analysis.

    Science.gov (United States)

    Kul, Seval; Savaş, Esen; Öztürk, Zeynel Abidin; Karadağ, Gülendam

    2014-06-01

    In this study, we conducted a meta-analysis of self-controlled cohort studies comparing body weights, blood levels of lipids and fasting blood glucose levels before and after Ramadan taking into account gender differences. Several databases were searched up to June 2012 for studies showing an effect of Ramadan fasting in healthy subjects, yielding 30 articles. The primary finding of this meta-analysis was that after Ramadan fasting, low-density lipoprotein (SMD = -1.67, 95 % CI = -2.48 to -0.86) and fasting blood glucose levels (SMD = -1.10, 95 % CI = -1.62 to -0.58) were decreased in both sex groups and also in the entire group compared to levels prior to Ramadan. In addition, in the female subgroup, body weight (SMD = -0.04, 95 % CI = -0.20, 0.12), total cholesterol (SMD = 0.05, 95 % CI = -0.51 to 0.60), and triglyceride levels (SMD = 0.03, 95 % CI = -0.31, 0.36) remained unchanged, while HDL levels (SMD = 0.86, 95 % CI = 0.11 to 1.61, p = 0.03) were increased. In males, Ramadan fasting resulted in weight loss (SMD = -0.24, 95 % CI = -0.36, -0.12, p = 0.001). Also, a substantial reduction in total cholesterol (SMD = -0.44, 95 % CI = -0.77 to -0.11) and LDL levels (SMD = -2.22, 95 % CI = -3.47 to -0.96) and a small decrease in triglyceride levels (SMD = -0.35, 95 % CI = -0.67 to -0.02) were observed in males. In conclusion, by looking at this data, it is evident that Ramadan fasting can effectively change body weight and some biochemical parameters in healthy subjects especially in males compared to pre-Ramadan period.

  13. Prediction of pKa Values for Druglike Molecules Using Semiempirical Quantum Chemical Methods.

    Science.gov (United States)

    Jensen, Jan H; Swain, Christopher J; Olsen, Lars

    2017-01-26

    Rapid yet accurate pK a prediction for druglike molecules is a key challenge in computational chemistry. This study uses PM6-DH+/COSMO, PM6/COSMO, PM7/COSMO, PM3/COSMO, AM1/COSMO, PM3/SMD, AM1/SMD, and DFTB3/SMD to predict the pK a values of 53 amine groups in 48 druglike compounds. The approach uses an isodesmic reaction where the pK a value is computed relative to a chemically related reference compound for which the pK a value has been measured experimentally or estimated using a standard empirical approach. The AM1- and PM3-based methods perform best with RMSE values of 1.4-1.6 pH units that have uncertainties of ±0.2-0.3 pH units, which make them statistically equivalent. However, for all but PM3/SMD and AM1/SMD the RMSEs are dominated by a single outlier, cefadroxil, caused by proton transfer in the zwitterionic protonation state. If this outlier is removed, the RMSE values for PM3/COSMO and AM1/COSMO drop to 1.0 ± 0.2 and 1.1 ± 0.3, whereas PM3/SMD and AM1/SMD remain at 1.5 ± 0.3 and 1.6 ± 0.3/0.4 pH units, making the COSMO-based predictions statistically better than the SMD-based predictions. For pK a calculations where a zwitterionic state is not involved or proton transfer in a zwitterionic state is not observed, PM3/COSMO or AM1/COSMO is the best pK a prediction method; otherwise PM3/SMD or AM1/SMD should be used. Thus, fast and relatively accurate pK a prediction for 100-1000s of druglike amines is feasible with the current setup and relatively modest computational resources.

  14. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang

    2006-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S - group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  15. Sodium methyldithiocarbamate inhibits MAP kinase activation through toll-like receptor 4, alters cytokine production by mouse peritoneal macrophages, and suppresses innate immunity.

    Science.gov (United States)

    Pruett, Stephen B; Zheng, Qiang; Schwab, Carlton; Fan, Ruping

    2005-09-01

    Sodium methyldithiocarbamate (SMD; trade name, Metam Sodium) is an abundantly used soil fumigant that can cause adverse health effects in humans, including some immunological manifestations. The mechanisms by which SMD acts, and its targets within the immune system are not fully understood. Initial experiments demonstrated that SMD administered by oral gavage substantially decreased IL-12 production and increased IL-10 production induced by lipopolysaccharide in mice. The present study was conducted to further characterize these effects and to evaluate our working hypothesis that the mechanism for these effects involves alteration in signaling through toll-like receptor 4 and that this would suppress innate immunity to infection. SMD decreased the activation of MAP kinases and AP-1 but not NF-kappaB in peritoneal macrophages. The expression of mRNA for IL-1alpha, IL-1beta, IL-18, IFN-gamma, IL-12 p35, IL-12 p40, and macrophage migration inhibitory factor (MIF) was inhibited by SMD, whereas mRNA for IL-10 was increased. SMD increased the IL-10 concentration in the peritoneal cavity and serum and decreased the concentration of IL-12 p40 in the serum, peritoneal cavity, and intracellularly in peritoneal cells (which are >80% macrophages). Similar effects on LPS-induced cytokine production were observed following dermal administration of SMD. The major breakdown product of SMD, methylisothiocyanate (MITC), caused similar effects on cytokine production at dosages as low as 17 mg/kg, a dosage relevant to human exposure levels associated with agricultural use of SMD. Treatment of mice with SMD decreased survival following challenge with non-pathogenic Escherichia coli within 24-48 h, demonstrating suppression of innate immunity.

  16. Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise M; Vaziri-Sani, Fariba; Delli, Ahmed

    2012-01-01

    The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D.......The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D....

  17. Radiometallating antibodies and biologically active peptides

    International Nuclear Information System (INIS)

    Mercer-Smith, J.A.; Roberts, J.C.; Lewis, D.; Newmyer, S.L.; Schulte, L.D.; Burns, T.P.; Mixon, P.L.; Jeffery, A.L.; Schreyer, S.A.; Cole, D.A.; Figard, S.D.; Lennon, V.A.; Hayashi, M.; Lavallee, D.K.

    1990-01-01

    We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N-benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have on functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies, and we have also developed methods to label smaller biologically active molecules, such as autoantigenic peptides. The autoantigenic peptides, fragments of the acetylcholine receptor, are under investigation for myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules and the radiometallation chemistry will be discussed

  18. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

  19. Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

    OpenAIRE

    Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

    2003-01-01

    In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

  20. Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.

    Science.gov (United States)

    Lucas, Bronwyn A; Lavi, Eitan; Shiue, Lily; Cho, Hana; Katzman, Sol; Miyoshi, Keita; Siomi, Mikiko C; Carmel, Liran; Ares, Manuel; Maquat, Lynne E

    2018-01-30

    Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs. To explore this possibility, we searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE and each regulated by SMD, by measuring changes in mRNA abundance after individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'-UTR SINEs that independently function in SMD control of myoblast metabolism. Expanding to other species, we demonstrated that SINE-directed SMD likely emerged in both primate and rodent lineages >20-25 million years ago. Our work reveals a mechanism for the convergent evolution of posttranscriptional gene regulatory networks in mammals by species-specific SINE transposition and SMD.

  1. Intranasal corticosteroids compared with oral antihistamines in allergic rhinitis

    DEFF Research Database (Denmark)

    Juel-Berg, Nanna; Darling, Peter; Bolvig, Julie

    2017-01-01

    to January 22, 2015. Criteria for eligibility were randomized controlled trials that compared the efficacy and/or adverse effects of INS and OA in patients with AR. Continuous outcome data were analyzed by using standardized mean differences (SMD) for multiple outcome measures, and mean differences...... score (SMD -0.70 [95% CI, -0.93 to -0.47]) and in relieving the following: nasal obstruction (SMD -0.56 [95% CI, -0.82 to -0.29]), rhinorrhea (SMD -0.47 [95% CI, -1.00 to 0.05]), nasal itching (SMD -0.42 [95% CI, -0.65 to -0.18]), sneezing (SMD -0.52 [95% CI, -0.73 to -0.32]), and quality of life mean...... difference -0.90 [95% CI, -1.18 to -0.62]). There was no difference in relief of ocular symptoms (SMD -0.08 [95% CI, -0.23 to 0.08]). In addition, four randomized controlled trials were included in a narrative analysis. The results in the narrative analysis were comparable with those found in the meta...

  2. Oxidative stress and sodium methyldithiocarbamate-induced modulation of the macrophage response to lipopolysaccharide in vivo.

    Science.gov (United States)

    Pruett, Stephen B; Cheng, Bing; Fan, Ruping; Tan, Wei; Sebastian, Thomas

    2009-06-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the United States, and hundreds of thousands of persons are exposed to this compound or its major breakdown product, methylisothiocyanate, at levels greater than recommended by the Environmental Protection Agency. A previous study suggests three mechanisms of action involved to some degree in the inhibition of inflammation and decreased resistance to infection caused by exposure of mice to the compound. One of these mechanisms is oxidative stress. The purpose of the present study was to confirm that this mechanism is involved in the effects of SMD on cytokine production by peritoneal macrophages and to further characterize its role in altered cytokine production. Results indicated that SMD significantly decreased the intracellular concentration of reduced glutathione (GSH), suggesting oxidative stress. This was further indicated by the upregulation of genes involved in the "response to oxidative stress" as determined by microarray analysis. These effects were associated with the inhibition of lipopolysaccharide (LPS)-induced production of several proinflammatory cytokines. Experimental depletion of GSH with buthionine sulfoximine (BSO) partially prevented the decrease in LPS-induced interleukin (IL)-6 production caused by SMD and completely prevented the decrease in IL-12. In contrast, BSO plus SMD substantially enhanced the production of IL-10. These results along with results from a previous study are consistent with the hypothesis that SMD causes oxidative stress, which contributes to modulation of cytokine production. However, oxidative stress alone cannot explain the increased IL-10 production caused by SMD.

  3. Serous Macular Detachment Associated with Dome-Shaped Macula and Tilted Disc

    Directory of Open Access Journals (Sweden)

    Diamar Pardo-López

    2011-03-01

    Full Text Available Introduction: An entirely new type of staphyloma has been recently described as dome-shaped macula (DSM. It is characterized by an abnormal convex macular contour within the concavity of a posterior staphyloma. We found DSM associated with serous macular detachment (SMD and tilted disc in two consecutive cases. Case Reports: Case 1: A 37-year-old female presented to our department because of sudden onset blurred vision in her right eye (OD. The best-corrected visual acuity (BCVA was 0.5 in both eyes. Funduscopy evidenced bilateral tilted disc associated with posterior staphyloma. Optical coherence tomography (OCT demonstrated a DSM with SMD in her OD. After 15 months of follow-up, BCVA of her OD remained stable with chronic SMD. Case 2: A 32-year-old female presented to our department because of blurred vision in her OD. The BCVA was 0.4 in the OD and 1.0 in the left eye (OS. Bilateral tilted disc and posterior staphyloma were evidenced in the funduscopy. OCT demonstrated a bilateral DSM with SMD in her OD. After 45 months of follow-up, two further episodes of transient SMD were observed in her OD and seven in her OS. The final BCVA was 0.63 in the OD and 0.8 in the OS. Discussion: SMD associated with tilted disc constitutes a potential cause of subretinal fluid accumulation in myopic patients. OCT is essential for the detection of both SMD and DSM.

  4. Parametric modulation of neural activity by emotion in youth with bipolar disorder, youth with severe mood dysregulation, and healthy volunteers.

    Science.gov (United States)

    Thomas, Laura A; Brotman, Melissa A; Muhrer, Eli J; Rosen, Brooke H; Bones, Brian L; Reynolds, Richard C; Deveney, Christen M; Pine, Daniel S; Leibenluft, Ellen

    2012-12-01

    CONTEXT Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm. OBJECTIVE To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs). DESIGN Case-control study. SETTING Government research institute. PARTICIPANTS Fifty-seven youths (19 BD, 15 SMD, and 23 HVs). MAIN OUTCOME MEASURE Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli. RESULTS In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions. CONCLUSIONS Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate

  5. Studies on surface-mounted SiPMs in 2015 testbeam of a highly granular hadron calorimeter

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Sascha [Institut fuer Physik, Johannes Gutenberg-Universitaet Mainz, Mainz (Germany); Collaboration: CALICE-D-Collaboration

    2016-07-01

    To achieve excellent jet energy resolution, a highly granular hadronic calorimeter is being developed within the CALICE collaboration. Therefore, about 8 million detector units consisting of scintillator tiles and silicon photomultipliers (SiPMs) will be installed in the final HCAL design. The usage of surface-mounted (SMD) SiPMs allows an automated mass assembly. During CERN SPS testbeam 2015, data for a prototype consisting of up to 11 layers of HCAL base units (HBU) was collected using electron, muon and pion beams. One of the layers was equipped with the first SMD HBU. Results and performance, especially of the SMD HBU are presented.

  6. Modeling root length density of field grown potatoes under different irrigation strategies and soil textures using artificial neural networks

    DEFF Research Database (Denmark)

    Ahmadi, Seyed Hamid; Sepaskhah, Ali Reza; Andersen, Mathias Neumann

    2014-01-01

    ) of the eight input variables: soil layer intervals (D), percentages of sand (Sa), silt (Si), and clay (Cl), bulk density of soil layers (Bd), weighted soil moisture deficit during the irrigation strategies period (SMD), geometric mean particle size diameter (dg), and geometric standard deviation (σg......). The results of the study showed that all the nine ANN models predicted the target RLD values satisfactorily with a correlation coefficient R2>0.98. The simplest and most complex ANN architectures were 3:2:1 and 5:5:1 consisting of D, SMD, dg, and D, Bd, SMD, σg, dg as the input variables, respectively. Low...

  7. Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies

    NARCIS (Netherlands)

    Steenbakkers, Peter G. A.; Baeten, Dominique; Rovers, Eric; Veys, Eric M.; Rijnders, Antonius W. M.; Meijerink, Jan; de Keyser, Filip; Boots, Annemieke M. H.

    2003-01-01

    Recently human cartilage gp-39 (HC gp-39) was identified as a candidate autoantigen in rheumatoid arthritis (RA). To further investigate the relevance of this Ag in RA, we have generated a set of five mAbs to a combination epitope of complexes of HC gp-39(263-275) and the RA-associated DR alpha beta

  8. Arabidopsis CDS blastp result: AK105677 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105677 001-201-B01 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediab...etic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting co

  9. Arabidopsis CDS blastp result: AK119376 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119376 001-132-A09 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediab...etic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting co

  10. Gclust Server: 97794 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 97794 CEL_B0244.2_25143920 Cluster Sequences Related Sequences(171) 767 ida-1: related to Islet cell Diabete...ida-1: related to Islet cell Diabetes Autoantigen family member (ida-1) Number of Sequences 1 Homologs 1 Clu

  11. Divergent frequencies of IGF-I receptor-expressing blood lymphocytes in monozygotic twin pairs discordant for Graves' disease: evidence for a phenotypic signature ascribable to nongenetic factors

    DEFF Research Database (Denmark)

    Douglas, Raymond S; Brix, Thomas H; Hwang, Catherine J

    2009-01-01

    CONTEXT: Graves' disease (GD) is an autoimmune process of the thyroid and orbital connective tissues. The fraction of T and B cells expressing IGF-I receptor (IGF-IR) is increased in GD. It is a potentially important autoantigen in GD. Susceptibility to GD arises from both genetic and acquired...

  12. Leiomodins: larger members of the tropomodulin (Tmod) gene family

    Science.gov (United States)

    Conley, C. A.; Fritz-Six, K. L.; Almenar-Queralt, A.; Fowler, V. M.

    2001-01-01

    The 64-kDa autoantigen D1 or 1D, first identified as a potential autoantigen in Graves' disease, is similar to the tropomodulin (Tmod) family of actin filament pointed end-capping proteins. A novel gene with significant similarity to the 64-kDa human autoantigen D1 has been cloned from both humans and mice, and the genomic sequences of both genes have been identified. These genes form a subfamily closely related to the Tmods and are here named the Leiomodins (Lmods). Both Lmod genes display a conserved intron-exon structure, as do three Tmod genes, but the intron-exon structure of the Lmods and the Tmods is divergent. mRNA expression analysis indicates that the gene formerly known as the 64-kDa autoantigen D1 is most highly expressed in a variety of human tissues that contain smooth muscle, earning it the name smooth muscle Leiomodin (SM-Lmod; HGMW-approved symbol LMOD1). Transcripts encoding the novel Lmod gene are present exclusively in fetal and adult heart and adult skeletal muscle, and it is here named cardiac Leiomodin (C-Lmod; HGMW-approved symbol LMOD2). Human C-Lmod is located near the hypertrophic cardiomyopathy locus CMH6 on human chromosome 7q3, potentially implicating it in this disease. Our data demonstrate that the Lmods are evolutionarily related and display tissue-specific patterns of expression distinct from, but overlapping with, the expression of Tmod isoforms. Copyright 2001 Academic Press.

  13. Antigen Loading (e.g., Glutamic Acid Decarboxylase 65) of Tolerogenic DCs (toIDCs) Reduces Their Capacity to Prevent Diabetes in the Non-Obese Diabetes (NOD)-Severe Combined Immunodeficiency Model of Adoptive Cotransfer of Diabetes As Well As in NOD Mice

    Czech Academy of Sciences Publication Activity Database

    Funda, David P.; Goliáš, Jaroslav; Hudcovic, Tomáš; Kozáková, Hana; Špíšek, R.; Palová-Jelínková, L.

    2018-01-01

    Roč. 9, FEB 16 (2018), č. článku 290. ISSN 1664-3224 R&D Projects: GA ČR GA15-24487S Institutional support: RVO:61388971 Keywords : type 1 diabetes * cell therapy * autoantigen Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 6.429, year: 2016

  14. Substitution of Pichia pastoris-derived recombinant proteins with mannose containing O- and N-linked glycans decreases specificity of diagnostic tests

    NARCIS (Netherlands)

    van Oort, Erica; Lerouge, Patrice; de Heer, Pleuni G.; Séveno, Martial; Coquet, Laurent; Modderman, Piet W.; Faye, Loïc; Aalberse, Rob C.; van Ree, Ronald

    2004-01-01

    Background: Recombinant proteins from Pichia pastoris need to be fully evaluated before used as diagnostic tools. Objective: The objective of this study was to investigate whether glycosylation by P. pastoris interferes with the specificity of diagnostic tests. Methods: An autoantigen involved in

  15. Disease: H00082 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0:397-409 (2004) DOI:10.1046/j.1365-2265.2004.01978.x ... PMID:12734493 (gene, env_factor, marker, autoantigen) ... AUTHORS ... Ai J, Leonha...rdt JM, Heymann WR. ... TITLE ... Autoimmune thyroid diseases: etiology, pathogenesis

  16. Protein microarray analysis as a tool for monitoring cellular autoreactivity in type 1 diabetes patients and their relatives

    Czech Academy of Sciences Publication Activity Database

    Vrábelová, Z.; Koloušková, S.; Böhmová, K.; Faresjo, M. K.; Sumnik, Z.; Pechová, M.; Kverka, Miloslav; Chudoba, D.; Zacharovová, K.; Stadlerová, G.; Pithová, P.; Hladíková, M.; Štechová, K.

    2007-01-01

    Roč. 8, - (2007), s. 252-260 ISSN 1399-543X Grant - others:GA MZd(CZ) NR8127 Institutional research plan: CEZ:AV0Z50200510 Source of funding: V - iné verejné zdroje Keywords : autoantigen * autoreactive t cells * cytokine Subject RIV: EE - Microbiology, Virology Impact factor: 2.314, year: 2007

  17. Natural antibodies related to metabolic and mammary health in dairy cows

    NARCIS (Netherlands)

    Knegsel, van A.T.M.; Hostens, M.; Vries Reilingh, de G.; Lammers, A.; Kemp, B.; Opsomer, G.; Parmentier, H.K.

    2012-01-01

    Natural antibodies (NAb) are defined as antibodies that circulate in normal healthy individuals under the absence of deliberate antigenic stimulation. Two types of NAb are distinguished: NAb towards exogenous antigens and NAb towards autoantigens (N(A)Ab). The objectives of the current study were

  18. Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity

    NARCIS (Netherlands)

    Amedei, Amedeo; Bergman, Mathijs P.; Appelmelk, Ben J.; Azzurri, Annalisa; Benagiano, Marisa; Tamburini, Carlo; van der Zee, Ruurd; Telford, John L.; Vandenbroucke-Grauls, Christina M. J. E.; D'Elios, Mario M.; del Prete, Gianfranco

    2003-01-01

    Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+-adenosine triphosphatase as autoantigen. Here, we report that H. pylori-infected patients with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells

  19. A NEW ELISA FOR THE DETECTION OF ANTI-HEPARAN SULFATE REACTIVITY, USING PHOTOBIOTINYLATED ANTIGEN

    NARCIS (Netherlands)

    HYLKEMA, MN; KRAMERS, C; VANDERWAL, TJ; VANBRUGGEN, MCJ; SWAAK, AJG; BERDEN, JHM; SMEENK, RJT; Hylkema, Machteld

    1994-01-01

    Autoantibodies reacting with a great variety of autoantigens are characteristic for the autoimmune disease systemic lupus erythematosus (SLE). Although reactivity with heparan sulfate (HS) in sera of patients with SLE is found in association with the occurrence of nephritis, the aetiological

  20. In vitro T lymphocyte responses to proteinase 3 (PR3) and linear peptides of PR3 in patients with Wegener's granulomatosis (WG)

    NARCIS (Netherlands)

    Van der Geld, YM; Huitema, MG; Franssen, CFM; Limburg, PC; Kallenberg, CGM; van der Zee, R.

    2000-01-01

    T cell-mediated immunity is thought to play an important role in the pathogenesis of WG. In previous studies a minority of WG patients as well as some healthy controls showed in vitro proliferation of their peripheral blood mononuclear cells (PBMC) to PR3, the main autoantigen in WG. The relevant

  1. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

    2015-01-01

    of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals...

  2. Antiplectin autoantibodies in subepidermal blistering diseases

    NARCIS (Netherlands)

    Buijsrogge, J. J. A.; de Jong, M. C. J. M.; Kloosterhuis, G. J.; Vermeer, M. H.; Koster, J.; Sonnenberg, A.; Jonkman, M. F.; Pas, H. H.

    2009-01-01

    Background Hemidesmosomal proteins may become targets of autoimmunity in subepidermal blistering diseases. Well-known recognized autoantigens are the intracellular plaque protein BP230, the transmembrane BP180 and its shed ecto-domain LAD-1. Objectives To establish the prevalence of autoimmunity

  3. Dendritic cells and veiled accessory macrophages : hormonal influences and autoimmune thyroid disease

    NARCIS (Netherlands)

    M.O. Canning (Martha)

    2005-01-01

    textabstractImmune responses to thyroid specific autoantigens form the basis of autoimmune thyroid disease pathogenesis. Two polar forms of autoimmune reactivity of the thyroid gland exist in this disease spectrum: a catabolic form characterized by gradual inflammatory destruction of thyroid

  4. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

    OpenAIRE

    McLachlan, Sandra M.; Rapoport, Basil

    2017-01-01

    Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyrotropin receptor (TSHR) A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of...

  5. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

  6. Thyroid peroxidase autoantibodies in euthyroid subjects

    NARCIS (Netherlands)

    Prummel, Mark F.; Wiersinga, Wilmar M.

    2005-01-01

    Thyroid peroxidase (TPO) is a key enzyme in the formation of thyroid hormones and a major autoantigen in autoimmune thyroid diseases. Titers of TPO antibodies also correlate with the degree of lymphocytic infiltration in euthyroid subjects, and they are frequently present in euthyroid subjects

  7. Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases.

    Science.gov (United States)

    Fridkis-Hareli, Masha

    2008-02-15

    Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature. Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies. Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes

  8. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

    Directory of Open Access Journals (Sweden)

    Sandra M. McLachlan

    2017-12-01

    Full Text Available Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg, thyroid peroxidase (TPO, and the thyrotropin receptor (TSHR A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of spontaneously arising pathogenic TSHR antibodies in transgenic human thyrotropin receptor/NOD.H2h4 mice by injecting a non-pathogenic form of TSHR A-subunit protein also provides evidence for original antigenic sin. From other studies, antigen presentation by B cells, not dendritic cells, is likely responsible for original antigenic sin. Recognition of restricted epitopes on the large glycosylated thyroid autoantigens (60-kDa A-subunit, 100-kDa TPO, and 600-kDa Tg facilitates exploring the amino acid locations in the immunodominant regions. Epitope spreading has also been revealed by autoantibodies in thyroid autoimmunity. In humans, and in mice that spontaneously develop autoimmunity to all three thyroid autoantigens, autoantibodies develop first to Tg and later to TPO and the TSHR A-subunit. The pattern of intermolecular epitope spreading is related in part to the thyroidal content of Tg, TPO and TSHR A-subunit and to the molecular sizes of these proteins. Importantly, the epitope spreading pattern provides a rationale for future antigen-specific manipulation to block the development of all thyroid autoantibodies by inducing tolerance to Tg, first in the autoantigen cascade. Because of its abundance, Tg may be the autoantigen of choice to explore antigen-specific treatment, preventing the development of pathogenic TSHR antibodies.

  9. 2015 Science Mission Directorate Technology Highlights

    Science.gov (United States)

    Seablom, Michael S.

    2016-01-01

    The role of the Science Mission Directorate (SMD) is to enable NASA to achieve its science goals in the context of the Nation's science agenda. SMD's strategic decisions regarding future missions and scientific pursuits are guided by Agency goals, input from the science community including the recommendations set forth in the National Research Council (NRC) decadal surveys and a commitment to preserve a balanced program across the major science disciplines. Toward this end, each of the four SMD science divisions -- Heliophysics, Earth Science, Planetary Science, and Astrophysics -- develops fundamental science questions upon which to base future research and mission programs. Often the breakthrough science required to answer these questions requires significant technological innovation, e.g., instruments or platforms with capabilities beyond the current state of the art. SMD's targeted technology investments fill technology gaps, enabling NASA to build the challenging and complex missions that accomplish groundbreaking science.

  10. The effects of cardiovascular exercise on human memory

    DEFF Research Database (Denmark)

    Roig, Marc; Nordbrandt, Sasja; Geertsen, Svend Sparre

    2013-01-01

    We reviewed the evidence for the use of cardiovascular exercise to improve memory and explored potential mechanisms. Data from 29 and 21 studies including acute and long-term cardiovascular interventions were retrieved. Meta-analyses revealed that acute exercise had moderate (SMD=0.26; 95% CI=0.0.......03, 0.49; p=0.03; N=22) whereas long-term had small (SMD=0.15; 95% CI=0.02, 0.27; p=0.02; N=37) effects on short-term memory. In contrast, acute exercise showed moderate to large (SMD=0.52; 95% CI=0.28, 0.75; p......We reviewed the evidence for the use of cardiovascular exercise to improve memory and explored potential mechanisms. Data from 29 and 21 studies including acute and long-term cardiovascular interventions were retrieved. Meta-analyses revealed that acute exercise had moderate (SMD=0.26; 95% CI=0...

  11. Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects

    DEFF Research Database (Denmark)

    Köhler, Ole; Benros, Michael E; Nordentoft, Merete

    2014-01-01

    -controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD...... investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.......08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant...

  12. Lift : Special Needs Transportation in Portland, Oregon

    Science.gov (United States)

    1978-01-01

    The report covers Portland, Oregon's Special Needs Transportation (SNT) project - the Lift - during its first year of operation. The purposes of this UMTA Service and Methods Demonstration (SMD) is to: (1) test a transit operator's ability to provide...

  13. High-Conductance Thermal Interfaces Based on Carbon Nanotubes, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The new devices and missions to achieve the aims of the NASA's Science Mission Directorate (SMD) are creating increasingly demanding thermal environments and...

  14. Influence of uncomplicated phacoemulsification on central macular thickness in diabetic patients: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jianping Liu

    Full Text Available To evaluate the effect of uncomplicated phacoemulsification on central macular thickness (CMT and best corrected visual acuity (BCVA in both diabetic patients without diabetic retinopathy (DR and diabetic patients with mild to moderate non-proliferative diabetic retinopathy (NPDR.Potential prospective observational studies were searched through PubMed and EMBASE. Standardized mean difference (SMD and 95% confidence interval (CI for changes in CMT and BCVA were evaluated at postoperative 1, 3 and 6 months. The pooled effect estimates were calculated in the use of a random-effects model.A total of 10 studies involving 190 eyes of diabetic patients without diabetic retinopathy and 143 eyes of diabetic patients with NPDR were identified. CMT values demonstrated a statistically significant increase after uncomplicated phacoemulsification at 1 month (SMD, -0.814; 95%CI, -1.230 to -0.399, 3 months (SMD, -0.565; 95%CI, -0.927 to -0.202 and 6 months (SMD, -0.458; 95%CI, -0.739 to -0.177 in diabetic patients with NPDR. There was no statistical difference in CMT values at postoperative 1 month (SMD, -1.206; 95%CI, -2.433 to 0.021and no statistically significant increase in CMT values at postoperative3 months (SMD, -0.535; 95%CI, -1.252 to 0.182 and 6 months (SMD, -1.181; 95%CI, -2.625 to 0.263 in diabetic patients without DR.BCVA was significantly increased at postoperative 1 month (SMD, 1.149; 95%CI, 0.251 to 2.047; and SMD,1.349; 95%CI, 0.264 to 2.434, respectively and 6 months (SMD, 1.295; 95%CI, 0.494 to 2.096; and SMD, 2.146; 95%CI, 0.172 to 4.120, respectively in both diabetic patients without DR and diabetic patients with NPDR. Sensitivity analysis showed that the results were relatively stable and reliable.Uncomplicated phacoemulsification in diabetic patients with mild to moderate NPDR seemed to influence significantly the subclinical thickening of the macular zones at postoperative 1, 3 and 6 months compared with diabetic patients without DR

  15. The design and construction of a double-sided Silicon Microvertex Detector for the L3 experiment at CERN

    International Nuclear Information System (INIS)

    Adam, A.; Ambrosi, G.; Babucci, E.; Bertucci, B.; Biasini, M.; Bilei, G.M.; Caria, M.; Checcucci, B.; Easo, S.; Fiandrini, E.; Krastev, V.R.; Massetti, R.; Pauluzzi, M.; Santocchia, A.; Servoli, L.; Baschirotto, A.; Bosetti, M.; Pensotti, S.; Rancoita, P.G.; Rattaggi, M.; Terzi, G.; Battiston, R.; Bay, A.; Burger, W.J.; Extermann, P.; Perrin, E.; Susinno, G.F.; Bencze, G.Y.L.; Kornis, J.; Toth, J.; Bobbink, G.J.; Duinker, P.; Brooks, M.L.; Coan, T.E.; Kapustinsky, J.S.; Kinnison, W.W.; Lee, D.M.; Mills, G.B.; Thompson, T.C.; Busenitz, J.; DiBitonto, D.; Camps, C.; Commichau, V.; Hangartner, K.; Schmitz, P.; Chen, A.; Hou, S.; Lin, W.T.; Gougas, A.; Kim, D.; Paul, T.; Hauviller, C.; Herve, A.; Josa, I.; Landi, G.; Lebeau, M.; Lecomte, P.; Viertel, G.M.; Waldmeier, S.; Leiste, R.; Lejeune, E.; Weill, R.; Lohmann, W.; Nowak, H.; Sachwitz, M.; Schoeniech, B.; Tonisch, F.; Trowitzsch, G.; Vogt, H.; Passaleva, G.; Yeh, S.C.

    1993-01-01

    A Silicon Microvertex Detector (SMD) has been commissioned for the L3 experiment at the Large Electron-Positron colliding-beam accelerator (LEP) at the European Center for Nuclear Physics, (CERN). The SMD is a 72,672 channel, two layer barrel tracker that is comprised of 96 ac-coupled, double-sided silicon detectors. Details of the design and construction are presented

  16. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies.

    Science.gov (United States)

    Rodríguez, Alexander J; Nunes, Vania dos Santos; Mastronardi, Claudio A; Neeman, Teresa; Paz-Filho, Gilberto J

    2016-03-01

    The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications. This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I(2) statistic. Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5-9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14-0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30-1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07-0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29-0.81, n=274; p1), macroalbuminuria (SMD=1.37; 95% CI=0.78-1.97, n=246; p1), neuropathy (SMD=0.25; 95% CI=0.14-0.36; n=1516; p1), and retinopathy (SMD=0.38; 95% CI=0.25-0.51; n=1306; p1). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size. Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Exercise-based cardiac rehabilitation in patients with heart failure

    DEFF Research Database (Denmark)

    Lewinter, Christian; Doherty, Patrick; Gale, Christopher P

    2015-01-01

    studies) was significantly reduced (RR ratio 0.65; 95% confidence interval (CI) 0.50-0.84; p = 0.001), but mortality (21 studies) was not (RR ratio 0.88; 95% CI 0.77-1.02; p = 0.08). The standardised exercise capacity (26 studies) showed a standardised mean difference (SMD) in favour of the exercise group...... as compared with the controls (SMD 0.98, 95% CI 0.59-1.37; p 

  18. Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis

    DEFF Research Database (Denmark)

    de Thurah, Annette; Esbensen, Bente Appel; Roelsgaard, Ida Kristiane

    2017-01-01

    difference (SMD) -0.17 (95 % CI -1.0 to 0.67), whereas a statistical significant difference in favour of nurse-led follow-up was seen after 2 years (SMD: 0.6 (95% CI -0.00 to 1.20)). CONCLUSION: After 1 year no difference in disease activity, indicated by DAS-28, were found between embedded nurse-led follow...

  19. Relationships between craniocervical posture and pain-related disability in patients with cervico-craniofacial pain

    Science.gov (United States)

    López-de-Uralde-Villanueva, Ibai; Beltran-Alacreu, Hector; Paris-Alemany, Alba; Angulo-Díaz-Parreño, Santiago; La Touche, Roy

    2015-01-01

    Objectives This cross-sectional correlation study explored the relationships between craniocervical posture and pain-related disability in patients with chronic cervico-craniofacial pain (CCFP). Moreover, we investigated the test–retest intrarater reliability of two craniocervical posture measurements: head posture (HP) and the sternomental distance (SMD). Methods Fifty-three asymptomatic subjects and 60 CCFP patients were recruited. One rater measured HP and the SMD using a cervical range of motion device and a digital caliper, respectively. The Spanish versions of the neck disability index and the craniofacial pain and disability inventory were used to assess pain-related disability (neck disability and craniofacial disability, respectively). Results We found no statistically significant correlations between craniocervical posture and pain-related disability variables (HP and neck disability [r=0.105; P>0.05]; HP and craniofacial disability [r=0.132; P>0.05]; SMD and neck disability [r=0.126; P>0.05]; SMD and craniofacial disability [r=0.195; P>0.05]). A moderate positive correlation was observed between HP and SMD for both groups (asymptomatic subjects, r=0.447; CCFP patients, r=0.52). Neck disability was strongly positively correlated with craniofacial disability (r=0.79; Pposture, but these differences were very small (mean difference =1.44 cm for HP; 6.24 mm for SMD). The effect sizes reached by these values were estimated to be small for SMD (d=0.38) and medium for HP (d=0.76). Conclusion The results showed no statistically significant correlations between craniocervical posture and variables of pain-related disability, but a strong correlation between the two variables of disability was found. Our findings suggest that small differences between CCFP patients and asymptomatic subjects exist with respect to the two measurements used to assess craniocervical posture (HP and SMD), and these measures demonstrated high test–retest intrarater reliability for

  20. Ecological aspects of pain in sensory modulation disorder.

    Science.gov (United States)

    Bar-Shalita, T; Deutsch, L; Honigman, L; Weissman-Fogel, I

    2015-01-01

    Sensory Modulation Disorder (SMD) interferes with the daily life participation of otherwise healthy individuals and is characterized by over-, under- or seeking responsiveness to naturally occurring sensory stimuli. Previous laboratory findings indicate pain hyper-sensitivity in SMD individuals suggesting CNS alteration in pain processing and modulation. However, laboratory studies lack ecological validity, and warrant clinical completion in order to elicit a sound understanding of the phenomenon studied. Thus, this study explored the association between sensory modulation and pain in a daily life context in a general population sample. Daily life context of pain and sensations were measured in 250 adults (aged 23-40 years; 49.6% males) using 4 self-report questionnaires: Pain Sensitivity Questionnaire (PSQ) and Pain Catastrophizing Scale (PCS) to evaluate the sensory and cognitive aspects of pain; the Sensory Responsiveness Questionnaire (SRQ) to appraise SMD; and the Short Form - 36 Health Survey, version 2 (SF36) to assess health related Quality of Life (QoL). Thirty two individuals (12.8%) were found with over-responsiveness type of SMD, forming the SOR-SMD group. While no group differences (SOR-SMD vs. Non-SMD) were found, low-to-moderate total sample correlations were demonstrated between the SRQ-Aversive sub-scale and i) PSQ total (r=0.31, pcognitive aspect. This indicates that SMD co-occurs with daily pain sensitivity, thus reducing QoL, but less with the cognitive-catastrophizing manifestation of pain perception. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The spray characteristic of gas-liquid coaxial swirl injector by experiment

    OpenAIRE

    Chen Chen; Zhihui Yan; Yang Yang; Hongli Gao; Shunhua Yang; Lei Zhang

    2017-01-01

    Using the laser phase Doppler particle analyzer (PDPA), the spray characteristics of gas-liquid coaxial swirl injector were studied. The Sauter mean diameter (SMD), axial velocity and size data rate were measured under different gas injecting pressure drop and liquid injecting pressure drop. Comparing to a single liquid injection, SMD with gas presence is obviously improved. So the gas presence has a significant effect on the atomization of the swirl injector. What’s more, the atomization eff...

  2. Effects of sodium methyldithiocarbamate on selected parameters of innate immunity and clearance of bacteria in a mouse model of sepsis.

    Science.gov (United States)

    Tan, Wei; Pruett, Stephen B

    2015-10-15

    Sodium methyldithiocarbamate (SMD), the third most widely used conventional pesticide in the United States, has been reported to inhibit several parameters associated with inflammation and to decrease resistance to infection. In a previous study, survival time was markedly decreased when mice were treated orally with SMD shortly before challenge with a high dose of Escherichia coli (E. coli) that was lethal to most of the control mice. In the present study, we evaluated selected parameters of the innate immune system using a lower challenge dose of E. coli, to determine which (if any) of these parameters reflected continued changes through 24h. Bacterial clearance from the peritoneal cavity, production of chemokines and cytokines, and body temperature were measured. All these parameters were reduced by SMD up to 12h after bacterial challenge, but the concentration of the anti-inflammatory cytokine IL-10 was increased. Even so, mice in the control and SMD-treated groups cleared most bacteria by 24h. Other parameters (cytokine concentrations and body temperature) were also normal or near normal by 24h. The same dosage of SMD administered intranasally also did not significantly decrease survival. Hypothermia from 16 to 28 h correlated with lethal outcome, but SMD significantly increased hypothermia only at 2 and 4h after challenge. In spite of substantial early inhibition by SMD of parameters known to be important for resistance to infection, bacterial clearance and survival were not altered, suggesting immunological reserve and/or rapid recovery after transient effects of SMD. Copyright © 2015. Published by Elsevier Inc.

  3. Exergaming as a viable therapeutic tool to improve static and dynamic balance among older adults and people with idiopathic Parkinson’s disease: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Dale Michael Harris

    2015-09-01

    Full Text Available The use of virtual reality games (known as ‘exergaming’ as a neurorehabilitation tool is gaining interest. Therefore, we aim to collate evidence for the effects of exergaming on the balance and postural control of older adults and people with idiopathic Parkinson’s disease (IPD. Six electronic databases were searched, from inception to April 2015, to identify relevant studies. Standardised mean differences (SMD and 95% confidence intervals (CI were used to calculate effect sizes between experimental and control groups. I2 statistics were used to determine levels of heterogeneity. 309 older adults and 74 people with IPD were assessed across eleven studies. The results showed that exergaming improved static balance (SMD 1.069, 95% CI 0.563 to 1.576, postural control (SMD 0.826, 95% CI 0.481 to 1.170 and dynamic balance (SMD -0.808, 95% CI -1.192 to -0.424 in healthy older adults. Two PD studies showed an improvement in static balance (SMD 0.124, 95% CI -0.581 to 0.828 and postural control (SMD 2.576, 95% CI 1.534 to 3.599. Our findings suggest that exergaming might be an appropriate therapeutic tool for improving balance and postural control in older adults, but more large-scale trials are needed to determine if the same is true for people with IPD.

  4. Inflammatory etiopathogenesis of systemic lupus erythematosus: an update

    Directory of Open Access Journals (Sweden)

    Podolska MJ

    2015-08-01

    Full Text Available Malgorzata J Podolska, Mona HC Biermann, Christian Maueröder, Jonas Hahn, Martin Herrmann Department of Internal Medicine 3, Institute for Clinical Immunology and Rheumatology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany Abstract: The immune system struggles every day between responding to foreign antigens and tolerating self-antigens to delicately maintain tissue homeostasis. If self-tolerance is broken, the development of autoimmunity can be the consequence, as it is in the case of the chronic inflammatory autoimmune disease systemic lupus erythematosus (SLE. SLE is considered to be a multifactorial disease comprising various processes and cell types that act abnormally and in a harmful way. Oxidative stress, infections, or, in general, tissue injury are accompanied by massive cellular demise. Several processes such as apoptosis, necrosis, or NETosis (formation of Neutrophil Extracellular Traps [NETs] may occur alone or in combination. If clearance of dead cells is insufficient, cellular debris may accumulate and trigger inflammation and leakage of cytoplasmic and nuclear autoantigens like ribonucleoproteins, DNA, or histones. Inadequate removal of cellular remnants in the germinal centers of secondary lymphoid organs may result in the presentation of autoantigens by follicular dendritic cells to autoreactive B cells that had been generated by chance during the process of somatic hypermutation (loss of peripheral tolerance. The improper exposure of nuclear autoantigens in this delicate location is consequently prone to break self-tolerance to nuclear autoantigens. Indeed, the germline variants of autoantibodies often do not show autoreactivity. The subsequent production of autoantibodies plays a critical role in the development of the complex immunological disorder fostering SLE. Immune complexes composed of cell-derived autoantigens and autoantibodies are formed and get deposited in various tissues, such as the

  5. Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome

    Science.gov (United States)

    Qin, Zongshi; Wu, Jiani; Tian, Jinhui; Zhou, Jing; Liu, Yali; Liu, Zhishun

    2016-01-01

    Alpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96–6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27–7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07–2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57–3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95–4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08–4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07–2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS. PMID:27759111

  6. Effectiveness of centre-based childcare interventions in increasing child physical activity: a systematic review and meta-analysis for policymakers and practitioners.

    Science.gov (United States)

    Finch, M; Jones, J; Yoong, S; Wiggers, J; Wolfenden, L

    2016-05-01

    The review describes the effectiveness of physical activity interventions implemented in centre-based childcare services and (i) examines characteristics of interventions that may influence intervention effects; (ii) describes the effects of pragmatic interventions and non-pragmatic interventions; (iii) assesses adverse effects; and (iv) describes cost-effectiveness of interventions Data sources were Cochrane Central Register of Controlled trials, MEDLINE, EMBASE, PsycINFO, ERIC, CINAHL, SCOPUS and SPORTDISCUS. Studies selected included randomized controlled trials conducted in centre-based childcare including an intervention to increase objectively measured physical activity in children aged less than 6 years. Data were converted into standardized mean difference (SMD) and analysed using a random effects model. Overall interventions significantly improved child physical activity (SMD 0.44; 95% confidence interval [CI]: 0.12-0.76). Significant effects were found for interventions that included structured activity (SMD 0.53; 95% CI: 0.12-0.94), delivery by experts (SMD 1.26; 95% CI: 0.20-2.32) and used theory (SMD 0.76; 95% CI: 0.08-1.44). Non-pragmatic (SMD 0.80; 95% CI: 0.12-1.48) but not pragmatic interventions (SMD 0.10; 95% CI:-0.13-0.33) improved child physical activity. One trial reported adverse events, and no trials reported cost data. Intervention effectiveness varied according to intervention and trial design characteristics. Pragmatic trials were not effective, and information on cost and adverse effects was lacking. Evidence gaps remain for policymakers and practitioners regarding the effectiveness and feasibility of childcare-based physical activity interventions. © 2016 World Obesity.

  7. Food insecurity among people with severe mental disorder in a rural Ethiopian setting: a comparative, population-based study.

    Science.gov (United States)

    Tirfessa, K; Lund, C; Medhin, G; Hailemichael, Y; Fekadu, A; Hanlon, C

    2017-11-16

    In low-income African countries, ensuring food security for all segments of the population is a high priority. Mental illness is associated consistently with poverty, but there is little evidence regarding the association with food insecurity. The aim of this study was to compare the levels of food insecurity in people with severe mental disorders (SMD) with the general population in a rural African setting with a high burden of food insecurity. Households of 292 community-ascertained people with a specialist-confirmed diagnosis of SMD (including schizophrenia and bipolar disorder) were compared with 284 households without a person with SMD in a rural district in south Ethiopia. At the time of the study, no mental health services were available within the district. Food insecurity was measured using a validated version of the Household Food Insecurity Access Scale. Disability was measured using the World Health Organisation Disability Assessment Schedule 2.0. Severe household food insecurity was reported by 32.5% of people with SMD and 15.9% of respondents from comparison households: adjusted odds ratio 2.82 (95% confidence interval 1.62 to 4.91). Higher annual income was associated independently with lower odds of severe food insecurity. When total disability scores were added into the model, the association between SMD and food insecurity became non-significant, indicating a possible mediating role of disability. Efforts to alleviate food insecurity need to target people with SMD as a vulnerable group. Addressing the disabling effects of SMD would also be expected to reduce food insecurity. Access to mental health care integrated into primary care is being expanded in this district as part of the Programme for Improving Mental health carE (PRIME). The impact of treatment on disability and food insecurity will be evaluated.

  8. A systematic review of factors associated with accidental falls in people with multiple sclerosis: a meta-analytic approach.

    Science.gov (United States)

    Giannì, Costanza; Prosperini, Luca; Jonsdottir, Johanna; Cattaneo, Davide

    2014-07-01

    To determine whether there are demographic, clinical, and instrumental variables useful to detect fall status of patients with multiple sclerosis. PubMed and the Cochrane Library. Eligible studies were identified by two independent investigators. Only studies having a clear distinction between fallers and non-fallers were included and meta-analysed. Odds ratios (ORs) and standard mean differences (SMDs) were calculated and pooled using fixed effect models. Among 115 screened articles, 15 fulfilled criteria for meta-analyses, with a total of 2425 patients included. Proportion of fallers may vary from 30% to 63% in a time frame from 1 to 12 months. No significant publication bias was found, even though 12/15 studies relied on retrospective reports of falls, thus introducing recall biases. Risk factors for falls varied across studies, owing to heterogeneity of populations included and clinical instruments used. The meta-analytic approach found that, compared with non-fallers, fallers had longer disease duration (SMD = 0.14, p = 0.02), progressive course of disease (OR = 2.02, p < 0.0001), assistive device for walking (OR = 3.16, p < 0.0001), greater overall disability level (SMD = 0.74, p < 0.0001), slower walking speed (SMD = 0.45, p = 0.0005), and worse performances in balance tests (Berg Balance Scale: SMD = -0.48, p = 0.002; Timed up-and-go test, SMD = 0.31, p = 0.04), and force-platform measures (postural sway) with eyes opened (SMD = 0.71, p = 0.006) and closed (SMD = 0.83, p = 0.01), respectively. Elucidations regarding risk factors for accidental falls in patients with multiple sclerosis (PwMs) are provided here, with worse disability score, progressive course, use of walking aid, and poorer performances in static and dynamic balance tests strongly associated with fall status. © The Author(s) 2014.

  9. Comparing Social Media Data and Survey Data in Assessing the Attractiveness of Beijing Olympic Forest Park

    Directory of Open Access Journals (Sweden)

    Zhifang Wang

    2018-02-01

    Full Text Available Together with the emerging popularity of big data in numerous studies, increasing theoretical discussions of the challenges and limitations of such data sources exist. However, there is a clear research gap in the empirical comparison studies on different data sources. The goal of this paper is to use “attractiveness” as a medium to examine the similarity and differences of Social media data (SMD and survey data in academic research, based on a case study of the Beijing Olympic Forest Park, in Beijing, China. SMD was extracted from two social media platforms and two surveys were conducted to assess the attractiveness of various locations and landscape elements. Data collection, keyword extraction and keyword prioritization were used and compared in the data gathering and analysis process. The findings revealed that SMD and survey data share many similarities. Both data sources confirm that natural ambience is more appreciated than cultural elements, particularly the naturalness of the park. Spaces of practical utility are more appreciated than facilities designed to have cultural meanings and iconic significance. Despite perceived similarities, this study concludes that SMD exhibits exaggerated and aggregated bias. This resulted from the intrinsic character of SMD as volunteered and unstructured data selected through an emotional process rather than from a rational synthesis. Exciting events were reported more often than daily experiences. Reflecting upon the strength and weakness of SMD and survey data, this study would recommend a combined landscape assessment process, which first utilizes SMD to build up an assessment framework, then applies conventional surveys for supplementary and detailed information. This would ultimately result in comprehensive understanding.

  10. Systematic review and meta-analysis shows a specific micronutrient profile in people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red blood cell copper and zinc, and higher salivary calcium and sodium.

    Directory of Open Access Journals (Sweden)

    Amene Saghazadeh

    Full Text Available Different metabolic profiles as well as comorbidities are common in people with Down Syndrome (DS. Therefore it is relevant to know whether micronutrient levels in people with DS are also different. This systematic review was designed to review the literature on micronutrient levels in people with DS compared to age and sex-matched controls without DS. We identified sixty nine studies from January 1967 to April 2016 through main electronic medical databases PubMed, Scopus, and Web of knowledge. We carried out meta-analysis of the data on four essential trace elements (Cu, Fe, Se, and Zn, six minerals (Ca, Cl, K, Mg, Na, and P, and five vitamins (vitamin A, B9, B12, D, and E. People with DS showed lower blood levels of Ca (standard mean difference (SMD = -0.63; 95% confidence interval (CI: -1.16 to -0.09, Se (SMD = -0.99; 95% CI: -1.55 to -0.43, and Zn (SMD = -1.30; 95% CI: -1.75 to -0.84, while red cell levels of Zn (SMD = 1.88; 95% CI: 0.48 to 3.28 and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57 were higher. They had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33 and Na (SMD = 1.04; 95% CI: 0.39 to 1.69. Our findings that micronutrient levels are different in people with DS raise the question whether these differences are related to the different metabolic profiles, the common comorbidities or merely reflect DS.

  11. The Immunomodulatory Effect of Acupoint Application for Childhood Asthma: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao Cun Yang

    2015-01-01

    Full Text Available Objective. To evaluate the evidence on the immunomodulatory effect of acupoint application for childhood asthma. Methods. Five electronic databases through October 2014 were searched. The risk of bias in eligible studies was assessed using the Cochrane Collaboration tool. Standardised mean difference (SMD and 95% confidence intervals (CI of random-effects model were calculated. And heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index. Results. Six studies were included in our review. The aggregated results suggested that acupoint application showed the beneficial effect for childhood asthma in improving IgA (SMD, −0.83; 95% CI −1.14 to −0.52; P<0.00001, IgE (SMD, −0.52; 95% CI −0.76 to −0.29; P<0.001, IgG (SMD, −1.17; 95% CI −1.61 to −0.74; P<0.0001, IL-4 (SMD, −0.57; 95% CI −0.91 to −0.23; P=0.0009, and IFN-γ (SMD, −0.38; 95% CI −0.71 to −0.04; P=0.03 but not IgM (SMD, −0.40; 95% CI −0.98 to 0.18; P=0.18. And the effective dose of acupoint application may be 2–6 hours/time and a total of 3 times within 4 weeks. Conclusions. This review showed the positive evidence that acupoint application had the favorable immunomodulatory effect for childhood asthma. However, more studies with long follow-up are warrant to confirm the current findings.

  12. Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors.

    Science.gov (United States)

    Leucht, Stefan; Leucht, Claudia; Huhn, Maximilian; Chaimani, Anna; Mavridis, Dimitris; Helfer, Bartosz; Samara, Myrto; Rabaioli, Matteo; Bächer, Susanne; Cipriani, Andrea; Geddes, John R; Salanti, Georgia; Davis, John M

    2017-10-01

    Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression. The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time. Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

  13. Massage Alleviates Delayed Onset Muscle Soreness after Strenuous Exercise: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jianmin Guo

    2017-09-01

    Full Text Available Purpose: The purpose of this systematic review and meta-analysis was to evaluate the effects of massage on alleviating delayed onset of muscle soreness (DOMS and muscle performance after strenuous exercise.Method: Seven databases consisting of PubMed, Embase, EBSCO, Cochrane Library, Web of Science, CNKI and Wanfang were searched up to December 2016. Randomized controlled trials (RCTs were eligible and the outcomes of muscle soreness, performance (including muscle maximal isometric force (MIF and peak torque and creatine kinase (CK were used to assess the effectiveness of massage intervention on DOMS.Results: Eleven articles with a total of 23 data points (involving 504 participants satisfied the inclusion criteria and were pooled in the meta-analysis. The findings demonstrated that muscle soreness rating decreased significantly when the participants received massage intervention compared with no intervention at 24 h (SMD: –0.61, 95% CI: –1.17 to –0.05, P = 0.03, 48 h (SMD: –1.51, 95% CI: –2.24 to –0.77, P < 0.001, 72 h (SMD: –1.46, 95% CI: –2.59 to –0.33, P = 0.01 and in total (SMD: –1.16, 95% CI: –1.60 to –0.72, P < 0.001 after intense exercise. Additionally, massage therapy improved MIF (SMD: 0.56, 95% CI: 0.21–0.90, P = 0.002 and peak torque (SMD: 0.38, 95% CI: 0.04–0.71, P = 0.03 as total effects. Furthermore, the serum CK level was reduced when participants received massage intervention (SMD: –0.64, 95% CI: –1.04 to –0.25, P = 0.001.Conclusion: The current evidence suggests that massage therapy after strenuous exercise could be effective for alleviating DOMS and improving muscle performance.

  14. Subjective memory and concentration deficits in medication-free, non-elderly Asians with major depressive disorder: prevalence and their correlates.

    Science.gov (United States)

    Srisurapanont, Manit; Bautista, Dianne; Chen, Chia-Hui; Wang, Gang; Udomratn, Pichet; Eurviriyanukul, Kanokkwan

    2015-01-15

    Subjective cognitive impairment (SCI) in major depressive disorder (MDD) is prevalent and correlated with disability. This study aimed to examine the prevalence rates and correlates of subjective memory deficit (SMD) and subjective concentration deficit (SCD) in medication-free, non-elderly Asians with MDD. The SMD and SCD were assessed by using two items of the Symptom Checklist-90-Revised (SCL-90-R). Other measurements of interest included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF-36). Adjusted odds ratios with 95% confidence intervals were calculated. Of 515 participants from China, Korea, Malaysia, Singapore, Taiwan, and Thailand, 347 (67.4%) and 377 (73.2%) had SMD and SCD, respectively. In total, 420 participants (81.6%) had SMD alone, SCD alone, and both deficits. Severe depression and poor mental health were significant correlates of SMD. Severe depression, clinically significant disability, poor physical health, and poor mental health were significantly independent correlates of SCD. Compared with young adults (18-34 years), older adults aged 50-65 years had a significantly lower risk of SCD (OR=.33, 95% CI: .19-.57). Only two SCL-90-R items were used to assess the SMD and SCD. The exclusion of MDD patients treated with psychotropic medications eliminated many patients commonly seen in typical clinic settings. SMD and SCD are prevalent in medication-free, non-elderly Asians with MDD. Both deficits are correlated with depression and mental health status. The independent correlation between SCD and disability underscores the crucial role of SCI in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The Effectiveness of Aromatherapy in Reducing Pain: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Shaheen E. Lakhan

    2016-01-01

    Full Text Available Background. Aromatherapy refers to the medicinal or therapeutic use of essential oils absorbed through the skin or olfactory system. Recent literature has examined the effectiveness of aromatherapy in treating pain. Methods. 12 studies examining the use of aromatherapy for pain management were identified through an electronic database search. A meta-analysis was performed to determine the effects of aromatherapy on pain. Results. There is a significant positive effect of aromatherapy (compared to placebo or treatments as usual controls in reducing pain reported on a visual analog scale (SMD = −1.18, 95% CI: −1.33, −1.03; p<0.0001. Secondary analyses found that aromatherapy is more consistent for treating nociceptive (SMD = −1.57, 95% CI: −1.76, −1.39, p<0.0001 and acute pain (SMD = −1.58, 95% CI: −1.75, −1.40, p<0.0001 than inflammatory (SMD = −0.53, 95% CI: −0.77, −0.29, p<0.0001 and chronic pain (SMD = −0.22, 95% CI: −0.49, 0.05, p=0.001, respectively. Based on the available research, aromatherapy is most effective in treating postoperative pain (SMD = −1.79, 95% CI: −2.08, −1.51, p<0.0001 and obstetrical and gynecological pain (SMD = −1.14, 95% CI: −2.10, −0.19, p<0.0001. Conclusion. The findings of this study indicate that aromatherapy can successfully treat pain when combined with conventional treatments.

  16. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    Science.gov (United States)

    Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

    1993-09-01

    Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

  17. Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands.

    Science.gov (United States)

    Green, Nathaniel M; Moody, Krishna-Sulayman; Debatis, Michelle; Marshak-Rothstein, Ann

    2012-11-16

    The key step in the activation of autoreactive B cells is the internalization of nucleic acid containing ligands and delivery of these ligands to the Toll-like Receptor (TLR) containing endolysosomal compartment. Ribonucleoproteins represent a large fraction of autoantigens in systemic autoimmune diseases. Here we demonstrate that many uridine-rich mammalian RNA sequences associated with common autoantigens effectively activate autoreactive B cells. Priming with type I IFN increased the magnitude of activation, and the range of which RNAs were stimulatory. A subset of RNAs that contain a high degree of self-complementarity also activated B cells through TLR3. For the RNA sequences that activated predominantly through TLR7, the activation is proportional to uridine-content, and more precisely defined by the frequency of specific uridine-containing motifs. These results identify parameters that define specific mammalian RNAs as ligands for TLRs.

  18. Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE.

    Science.gov (United States)

    Casciola-Rosen, L; Rosen, A

    1997-01-01

    Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.

  19. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

    DEFF Research Database (Denmark)

    Volck, B; Price, P A; Johansen, J S

    1998-01-01

    YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function...... of patients with RA, and the cells are assumed to play a role in joint destruction in that disorder. Therefore, we examined whether neutrophils are a source of YKL-40. YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase...... YKL-40 at the myelocyte-metamyelocyte stage, the stage of maturation at which other specific granule proteins are formed. Assuming that YKL-40 has a role as an autoantigen in RA by inducing T cell-mediated autoimmune response, YKL-40 released from neutrophils in the inflamed joint could be essential...

  20. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

    Directory of Open Access Journals (Sweden)

    Chaojun Hu

    Full Text Available Autoantibodies in cerebrospinal fluid (CSF from patients with neuropsychiatric systemic lupus erythematosus (NPSLE may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosuspatients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43.Anti-proliferating cell nuclear antigen (PCNA was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A. The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045.Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009. Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

  1. Nonelectrophoretic bidirectional transfer of a single SDS-PAGE gel with multiple antigens to obtain 12 immunoblots.

    Science.gov (United States)

    Kurien, Biji T; Scofield, R Hal

    2009-01-01

    Protein blotting is an invaluable technique in immunology to detect and characterize proteins of low abundance. Proteins resolved on sodium dodecyl sulfate (SDS) polyacrylamide gels are normally transferred electrophoretically to adsorbent membranes such as nitrocellulose or polyvinylidene diflouride membranes. Here, we describe the nonelectrophroretic transfer of the Ro 60 (or SSA) autoantigen, 220- and 240-kD spectrin antigens, and prestained molecular weight standards from SDS polyacrylamide gels to obtain up to 12 immunoblots from a single gel and multiple sera.

  2. Relationship between ZnT8Ab, the SLC30A8 gene and disease progression in children with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lotte B; Vaziri-Sani, Fariba; Pörksen, Sven

    2011-01-01

    Autoantibodies against the newly established autoantigen in type 1 diabetes, zinc transporter 8, ZnT8, are presented as two types, ZnT8RAb and ZnT8WAb. The rs13266634 variant of the SLC30A8 gene has recently been found to determine the type of ZnT8Ab. The aim of this study was to explore the impact...

  3. Progress in the biological function of alpha-enolase

    Directory of Open Access Journals (Sweden)

    Hong Ji

    2016-03-01

    Full Text Available Alpha-enolase (ENO1, also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. It is a multifunctional glycolytic enzyme involved in cellular stress, bacterial and fungal infections, autoantigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, development and reproduction of organisms. This article mainly reviews the basic characteristics and biological functions of ENO1.

  4. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison's disease.

    OpenAIRE

    Winqvist, O; Gustafsson, J; Rorsman, F; Karlsson, F A; Kämpe, O

    1993-01-01

    Autoimmune polyendocrine syndrome type I (APS I) and idiopathic Addison's disease are both disorders with adrenal insufficiency but with differences in genetic background, clinical presentation, and extent of extraadrenal manifestations. In this study the major adrenal autoantigen identified with sera from patients with APS I was characterized by analyses using indirect immunofluorescence, Western blots of adrenal subcellular fractions and of recombinant proteins, immunoprecipitations of [35S...

  5. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease

    DEFF Research Database (Denmark)

    Husby, S; Koletzko, S; Korponay-Szabó, I R

    2012-01-01

    Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather...... uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved....

  6. Prohibitin Is Involved in Patients with IgG4 Related Disease.

    Directory of Open Access Journals (Sweden)

    Hongwu Du

    Full Text Available IgG4-related disease (IgG4-RD is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD.Multiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples.One positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%, Mikulicz's disease (8/15; 53.3%, retroperitoneal fibrosis (6/11; 54.5%, other probable IgG4-RD (26/29; 89.7% and Sjögren's syndrome (4/30; 13.3% but not in apparently healthy donors (1/70; 1.4%.An association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz's disease and retroperitoneal fibrosis.

  7. The Emerging Importance of Non-HLA Autoantibodies in Kidney Transplant Complications

    OpenAIRE

    Cardinal, Héloise; Dieudé, Mélanie; Hébert, Marie-Josée

    2016-01-01

    Antibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular ...

  8. Association of immune response to endothelial cell growth factor with early disseminated and late manifestations of Lyme disease but not posttreatment Lyme disease syndrome.

    Science.gov (United States)

    Tang, Kevin S; Klempner, Mark S; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2015-12-01

    Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis.

    Science.gov (United States)

    Langebeek, Nienke; Gisolf, Elizabeth H; Reiss, Peter; Vervoort, Sigrid C; Hafsteinsdóttir, Thóra B; Richter, Clemens; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

    2014-08-21

    Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adherence. We searched PubMed for original English-language papers, published between 1996 and June 2014, and the reference lists of all relevant articles found. Studies reporting on predictors/correlates of adherence of adults prescribed ART for chronic HIV infection were included without restriction to adherence assessment method, study design or geographical location. Two researchers independently extracted the data from the same papers. Random effects models with inverse variance weights were used to aggregate findings into pooled effects estimates with 95% confidence intervals. The standardized mean difference (SMD) was used as the common effect size. The impact of study design features (adherence assessment method, study design, and the United Nations Human Development Index (HDI) of the country in which the study was set) was investigated using categorical mixed effects meta-regression. In total, 207 studies were included. The following predictors/correlates were most strongly associated with adherence: adherence self-efficacy (SMD = 0.603, P = 0.001), current substance use (SMD = -0.395, P = 0.001), concerns about ART (SMD = -0.388, P = 0.001), beliefs about the necessity/utility of ART (SMD = 0.357, P = 0.001), trust/satisfaction with the HIV care provider (SMD = 0.377, P = 0.001), depressive symptoms (SMD = -0.305, P = 0.001), stigma about HIV (SMD = -0.282, P = 0.001), and social support (SMD = 0.237, P = 0.001). Smaller but significant associations were observed for the

  10. Video-assisted Thoracoscope versus Video-assisted Mini-thoracotomy for Non-small Cell Lung Cancer: A Meta-analysis

    Directory of Open Access Journals (Sweden)

    Bing WANG

    2017-05-01

    Full Text Available Background and objective The aim of this study is to assess the effect of video-assisted thoracoscopic surgery (VATS and video-assisted mini-thoracotomy (VAMT in the treatment of non-small cell lung cancer (NSCLC. Methods We searched PubMed, EMbase, CNKI, VIP and ISI Web of Science to collect randomized controlled trials (RCTs of VATS versus VAMT for NSCLC. Each database was searched from May 2006 to May 2016. Two reviewers independently assessed the quality of the included studies and extracted relevant data, using RevMan 5.3 meta-analysis software. Results We finally identified 13 RCTs involving 1,605 patients. There were 815 patients in the VATS group and 790 patients in the VAMT group. The results of meta-analysis were as follows: statistically significant difference was found in the harvested lymph nodes (SMD=-0.48, 95%CI: -0.80--0.17, operating time (SMD=13.56, 95%CI: 4.96-22.16, operation bleeding volume (SMD=-33.68, 95%CI: -45.70--21.66, chest tube placement time (SMD=-1.05, 95%CI: -1.48--0.62, chest tube drainage flow (SMD=-83.69, 95%CI: -143.33--24.05, postoperative pain scores (SMD=-1.68, 95%CI: -1.98--1.38 and postoperative hospital stay (SMD=-2.27, 95%CI: -3.23--1.31. No statistically significant difference was found in postoperative complications (SMD=0.83, 95%CI: 0.54-1.29 and postoperative mortality (SMD=0.95, 95%CI: 0.55-1.63 between videoassisted thoracoscopic surgery lobectomy and video-assisted mini-thoracotomy lobectomy in the treatment of NSCLC. Conclusion Compared with video-assisted mini-thoracotomy lobectomy in the treatment of non-small cell lung cancer, the amount of postoperative complications and postoperative mortality were almost the same in video-assisted thoracoscopic lobectomy, but the amount of harvested lymph nodes, operating time, blood loss, chest tube drainage flow, and postoperative hospital stay were different. VATS is safe and effective in the treatment of NSCLC.

  11. Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis.

    Science.gov (United States)

    Dillon, David G; Gurdasani, Deepti; Riha, Johanna; Ekoru, Kenneth; Asiki, Gershim; Mayanja, Billy N; Levitt, Naomi S; Crowther, Nigel J; Nyirenda, Moffat; Njelekela, Marina; Ramaiya, Kaushik; Nyan, Ousman; Adewole, Olanisun O; Anastos, Kathryn; Azzoni, Livio; Boom, W Henry; Compostella, Caterina; Dave, Joel A; Dawood, Halima; Erikstrup, Christian; Fourie, Carla M; Friis, Henrik; Kruger, Annamarie; Idoko, John A; Longenecker, Chris T; Mbondi, Suzanne; Mukaya, Japheth E; Mutimura, Eugene; Ndhlovu, Chiratidzo E; Praygod, George; Pefura Yone, Eric W; Pujades-Rodriguez, Mar; Range, Nyagosya; Sani, Mahmoud U; Schutte, Aletta E; Sliwa, Karen; Tien, Phyllis C; Vorster, Este H; Walsh, Corinna; Zinyama, Rutendo; Mashili, Fredirick; Sobngwi, Eugene; Adebamowo, Clement; Kamali, Anatoli; Seeley, Janet; Young, Elizabeth H; Smeeth, Liam; Motala, Ayesha A; Kaleebu, Pontiano; Sandhu, Manjinder S

    2013-12-01

    Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings

  12. Effects of different lower-limb sensory stimulation strategies on postural regulation-A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Mei Teng Woo

    Full Text Available Systematic reviews of balance control have tended to only focus on the effects of single lower-limb stimulation strategies, and a current limitation is the lack of comparison between different relevant stimulation strategies. The aim of this systematic review and meta-analysis was to examine evidence of effects of different lower-limb sensory stimulation strategies on postural regulation and stability. Moderate- to high- pooled effect sizes (Unbiased (Hedges' g standardized mean differences (SMD = 0.31-0.66 were observed with the addition of noise in a Stochastic Resonance Stimulation Strategy (SRSS, in three populations (i.e., healthy young adults, older adults, and individuals with lower-limb injuries, and under different task constraints (i.e., unipedal, bipedal, and eyes open. A Textured Material Stimulation Strategy (TMSS enhanced postural control in the most challenging condition-eyes-closed on a stable surface (SMD = 0.61, and in older adults (SMD = 0.30. The Wearable Garments Stimulation Strategy (WGSS showed no or adverse effects (SMD = -0.68-0.05 under all task constraints and in all populations, except in individuals with lower-limb injuries (SMD = 0.20. Results of our systematic review and meta-analysis revealed that future research could consider combining two or more stimulation strategies in intervention treatments for postural regulation and balance problems, depending on individual needs.

  13. Enhancing the Impact of NASA Astrophysics Education and Public Outreach: Sharing Best Practices

    Science.gov (United States)

    Bartolone, Lindsay; Smith, D. A.; Astrophysics Science Education, NASA; Public Outreach Forum Team

    2013-01-01

    The NASA Science Education and Public Outreach Forums support the NASA Science Mission Directorate (SMD) and its education and public outreach community in enhancing the coherence, efficiency, and effectiveness of SMD-funded education and public outreach programs. As part of this effort, the four Forums (Astrophysics, Earth Science, Heliophysics, and Planetary Science) work together to coordinate resources and opportunities that enable sharing of best practices relevant to SMD-funded education and public outreach. Efforts include collaborating with SMD-funded education and public outreach programs to identify community needs for professional development; raising awareness of the existing body of best practices and educational research; and, organizing distance learning and face-to-face professional development opportunities. Topics include best practices in navigating NASA SMD education and public outreach program requirements, social media, engaging girls in science, and student misconceptions / reasoning difficulties. Opportunities to share best practices and learn from experts are extended to the broader astronomy and astrophysics community through the annual Astronomical Society of the Pacific education and public outreach conference. Evaluation of community professional development resources and opportunities is in progress.

  14. Neural circuitry of masked emotional face processing in youth with bipolar disorder, severe mood dysregulation, and healthy volunteers

    Directory of Open Access Journals (Sweden)

    Laura A. Thomas

    2014-04-01

    Full Text Available Youth with bipolar disorder (BD and those with severe, non-episodic irritability (severe mood dysregulation, SMD show face-emotion labeling deficits. These groups differ from healthy volunteers (HV in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N = 20, SMD (N = 18, and HV (N = 22 during “Aware” and “Non-aware” priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face (angry, fearful, happy, neutral, blank oval appeared (187 ms before the shape. In non-aware, a face appeared (17 ms, followed by a mask (170 ms, and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders.

  15. Neural circuitry of masked emotional face processing in youth with bipolar disorder, severe mood dysregulation, and healthy volunteers.

    Science.gov (United States)

    Thomas, Laura A; Brotman, Melissa A; Bones, Brian L; Chen, Gang; Rosen, Brooke H; Pine, Daniel S; Leibenluft, Ellen

    2014-04-01

    Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show face-emotion labeling deficits. These groups differ from healthy volunteers (HV) in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N=20), SMD (N=18), and HV (N=22) during "Aware" and "Non-aware" priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face (angry, fearful, happy, neutral, blank oval) appeared (187 ms) before the shape. In non-aware, a face appeared (17 ms), followed by a mask (170 ms), and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

    DEFF Research Database (Denmark)

    Galling, B; Vernon, J A; Pagsberg, A K

    2018-01-01

    adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval...... (CI) = -0.57 to -0.17, P SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.......42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0...

  17. Effect of anti-inflammatory treatment on depression, depressive symptoms and side effects: A systematic review and meta-analysis of randomized clinical trials

    DEFF Research Database (Denmark)

    Köhler, Karl Ole

    2014-01-01

    of pharmacological anti-inflammatory treatment in adults with depressive symptoms including adults who fulfill criteria for depression. Data Extraction and Synthesis: Data were extracted by two independent reviewers. Pooled standard mean difference (SMD) and Odds Ratios (OR) were calculated. Main Outcome Measures...... depressive symptoms (SMD=-0.34; 95%-CI: -0.57 to -0.11; I2=90%) compared to placebo. This effect was observed both in studies including patients with depression (SMD=-0.54; 95%-CI: -1.08 to -0.01; I2=68%) and depressive symptoms (SMD=-0.27; 95%-CI: -0.53 to -0.01; I2=93%). The heterogeneity of the studies...... was not explained by differences in inclusion of clinical depression versus depressive symptoms or NSAIDs versus cytokine inhibitors. Sub-analyses particularly emphasized antidepressant properties for the selective COX-2 inhibitor celecoxib in general (SMD=-0.29; 95%-CI: -0.49 to -0.08; I2=73%), on remission (OR=7...

  18. Early sitting, standing, and walking in conjunction with contemporary Bobath approach for stroke patients with severe motor deficit.

    Science.gov (United States)

    Tang, Qingping; Tan, Lihong; Li, Baojun; Huang, Xiaosong; Ouyang, Chunhong; Zhan, Hailan; Pu, Qinqin; Wu, Lixiang

    2014-01-01

    The commonly used therapeutic approach, the contemporary Bobath approach (CBA), is not sufficient to restore independent locomotion for individuals with severe motor deficit (SMD) after stroke. Therefore, we propose that the early sitting, standing, and walking in conjunction with the CBA (ECBA) be used to treat individuals with SMD after stroke. To investigate whether ECBA may enhance mobility and balance in subjects with SMD after stroke. Thirty-three men and 15 women, aged 60 to 74 years, with SMD after stroke were recruited for the study. CBA or ECBA was performed with the subjects 5 times per week in 50-minute sessions for 8 weeks. The Stroke Rehabilitation Assessment of Movement (STREAM) and the Berg Balance Scale were implemented before treatment and at 4 and 8 weeks after treatment, respectively. The STREAM scores indicated that ECBA was more efficient than the CBA intervention for lower extremity mobility, F(1, 46) = 24.0, P < .001, and basic mobility, F(1, 46) = 102.6, P < .001. Overall STREAM scores were higher in the ECBA group, F(1, 46) =24.1, P < .001, after 8 weeks of therapy. Balance scores of the ECBA subjects were higher than those of the CBA subjects after 8 weeks of therapy, F(1, 46) = 73.1, P < .001. However, there was no difference in upper extremity mobility between the 2 groups. ECBA is a valuable intervention to improve lower extremity mobility, basic mobility, and balance ability for individuals with SMD after stroke.

  19. Do We Really Know How to Treat a Child with Bipolar Disorder or One with Severe Mood Dysregulation? Is There a Magic Bullet?

    Directory of Open Access Journals (Sweden)

    Rajeev Jairam

    2012-01-01

    Full Text Available Background. Despite controversy, bipolar disorder (BD is being increasingly diagnosed in under 18s. There is scant information regarding its treatment and uncertainty regarding the status of “severe mood dysregulation (SMD” and how it overlaps with BD. This article collates available research on treatment of BD in under 18s and explores the status of SMD. Methods. Literature on treatment of BD in under 18s and on SMD were identified using major search engines; these were then collated and reviewed. Results. Some markers have been proposed to differentiate BD from disruptive behaviour disorders (DBD in children. Pharmacotherapy restricted to short-term trials of mood-stabilizers and atypical-antipsychotics show mixed results. Data on maintenance treatment and non-pharmacological interventions are scant. It is unclear whether SMD is an independent disorder or an early manifestation of another disorder. Conclusions. Valproate, lithium, risperidone, olanzapine, aripiprazole and quetiapine remain first line treatments for acute episodes in the under 18s with BD. Their efficacy in maintenance treatment remains unclear. There is no validated treatment for SMD. It is likely that some children who are currently diagnosed with BD and DBD and possibly most children currently diagnosed with SMD will be subsumed under the proposed category in the DSM V of disruptive mood dysregulation disorder with dysphoria.

  20. Are exercise programs effective for improving health-related quality of life among cancer survivors? A systematic review and meta-analysis.

    Science.gov (United States)

    Mishra, Shiraz I; Scherer, Roberta W; Snyder, Claire; Geigle, Paula; Gotay, Carolyn

    2014-11-01

    To evaluate the effectiveness of exercise interventions on overall health-related quality of life (HRQOL) and its domains among cancer survivors who have completed primary treatment. 11 electronic databases were searched from inception (dates varied) to October 2011. The authors also identified eligible trials through a search of additional sources. 40 trials with 3,694 participants met the inclusion criteria. At 12 weeks, cancer survivors exposed to exercise interventions had greater positive improvement in overall HRQOL (standardized mean difference [SMD] 0.48; 95% confidence interval [CI] [0.16, 0.81]), emotional well-being (SMD 0.33; 95% CI [0.05, 0.61]), and social functioning (SMD 0.45; 95% CI [0.02, 0.87]); and had a significant reduction in anxiety (SMD -0.26; 95% CI [-0.44, -0.07]) and fatigue (SMD -0.82; 95% CI [-1.5, -0.14]). Exercise programs have a beneficial effect on HRQOL and most of its domains and can be integrated into the management plans for cancer survivors who have completed treatment. Future research is needed to help understand specific attributes of exercise programs that are beneficial for improving HRQOL within and across cancer types. Evidence presented in this review supports the inclusion of exercise programs in clinical guidelines for the management of cancer survivors who have completed treatment, such as the Oncology Nursing Society's Putting Evidence Into Practice resource.

  1. Effects of different lower-limb sensory stimulation strategies on postural regulation-A systematic review and meta-analysis.

    Science.gov (United States)

    Woo, Mei Teng; Davids, Keith; Liukkonen, Jarmo; Orth, Dominic; Chow, Jia Yi; Jaakkola, Timo

    2017-01-01

    Systematic reviews of balance control have tended to only focus on the effects of single lower-limb stimulation strategies, and a current limitation is the lack of comparison between different relevant stimulation strategies. The aim of this systematic review and meta-analysis was to examine evidence of effects of different lower-limb sensory stimulation strategies on postural regulation and stability. Moderate- to high- pooled effect sizes (Unbiased (Hedges' g) standardized mean differences (SMD) = 0.31-0.66) were observed with the addition of noise in a Stochastic Resonance Stimulation Strategy (SRSS), in three populations (i.e., healthy young adults, older adults, and individuals with lower-limb injuries), and under different task constraints (i.e., unipedal, bipedal, and eyes open). A Textured Material Stimulation Strategy (TMSS) enhanced postural control in the most challenging condition-eyes-closed on a stable surface (SMD = 0.61), and in older adults (SMD = 0.30). The Wearable Garments Stimulation Strategy (WGSS) showed no or adverse effects (SMD = -0.68-0.05) under all task constraints and in all populations, except in individuals with lower-limb injuries (SMD = 0.20). Results of our systematic review and meta-analysis revealed that future research could consider combining two or more stimulation strategies in intervention treatments for postural regulation and balance problems, depending on individual needs.

  2. Bone mineral density, osteoporosis, and fractures among people with eating disorders: a systematic review and meta-analysis.

    Science.gov (United States)

    Solmi, M; Veronese, N; Correll, C U; Favaro, A; Santonastaso, P; Caregaro, L; Vancampfort, D; Luchini, C; De Hert, M; Stubbs, B

    2016-05-01

    To provide meta-analytical evidence of bone mineral density (BMD), fractures, and osteoporosis rates in eating disorders (ED) vs. healthy controls (HCs). Three independent authors searched major electronic databases from inception till August 2015 for cross-sectional studies reporting BMD in people with ED (anorexia nervosa, (AN); bulimia nervosa, (BN); eating disorders not otherwise specified, (EDNOS)) vs. HCs. Standardized mean differences (SMDs) ±95% and confidence intervals (CIs) were calculated for BMD, and odds ratios (ORs) for osteopenia, osteoporosis, and fractures. Overall, 57 studies were eligible, including 21 607 participants (ED = 6485, HCs = 15 122). Compared to HC, AN subjects had significantly lower BMD values at lumbar spine (SMD = -1.51, 95% CI = -1.75, -1.27, studies = 42), total hip (SMD = -1.56, 95%CI = -1.84, -1.28, studies = 23), intertrochanteric region (SMD = -1.80, 95%CI = -2.46, -1.14, studies = 7), trochanteric region (SMD = -1.05, 95%CI = -1.44, -0.66, studies = 7), and femoral neck (SMD = -0.98, 95%CI = -1.12, -0.77, studies = 20). Reduced BMD was moderated by ED illness duration and amenorrhea (P EDNOS vs. HC. People with AN have reduced BMD, increased odds of osteoporosis and risk of fractures. Proactive monitoring and interventions are required to ameliorate bone loss in AN. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection: A PRISMA-compliant study.

    Science.gov (United States)

    Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

    2017-07-01

    The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Six studies (360 RTRs) were included. Two hundred thirty six RTRs (98.3%) achieved sustained virological response within 12 weeks; HCV infection was cleared in 239 RTRs after 24-week treatment. Liver function differed significantly pre- and posttreatment (alanine aminotransferase, SMD: 0.96, 95%CIs: 0.65, 1.26; aspartate aminotransferase, SMD: 0.89, 95%CIs: 0.60, 1.18); allograft function pre- and posttreatment was not statistically different (serum creatinine, SMD: -0.13, 95%CIs: -0.38, 0.12; estimated glomerular filtration rate, SMD: 0.20, 95%CIs: -0.11, 0.51). General symptoms (fatigue nausea dizziness or headache) were the most common adverse events (AEs) (39.3%). Severe AEs, that is, anemia, portal vein thrombosis, and streptococcus bacteraemia and pneumonia, were present in 1.1%, 0.6%, and 1.1% of RTRs, respectively. Our findings suggest that DAAs are highly efficacious and safe for treating HCV-infected RTRs and without significant AE.

  4. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-06

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (piAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  5. Esophageal hypomotility and spastic motor disorders: current diagnosis and treatment.

    Science.gov (United States)

    Valdovinos, Miguel A; Zavala-Solares, Monica R; Coss-Adame, Enrique

    2014-11-01

    Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis, either from a reduction or absence of contractions, whereas spastic motor disorders (SMD) are characterized by an increase in the vigor and/or propagation velocity of esophageal body contractions. Their pathophysiology is not clearly known. The reduced excitation of the smooth muscle contraction mediated by cholinergic neurons and the impairment of inhibitory ganglion neuronal function mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent clinical manifestations for both of these dysfunctions, and gastroesophageal reflux disease (GERD) is commonly associated with these motor disorders. The introduction of high-resolution manometry (HRM) and esophageal pressure topography (EPT) has significantly enhanced the ability to diagnose EH and SMD. Novel EPT metrics in particular the development of the Chicago Classification of esophageal motor disorders has enabled improved characterization of these abnormalities. The first step in the management of EH and SMD is to treat GERD, especially when esophageal testing shows pathologic reflux. Smooth muscle relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors) and pain modulators may be useful in the management of dysphagia or pain in SMD. Endoscopic Botox injection and pneumatic dilation are the second-line therapies. Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may be considered in highly selected cases but lack evidence.

  6. Exergaming as a Viable Therapeutic Tool to Improve Static and Dynamic Balance among Older Adults and People with Idiopathic Parkinson’s Disease: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Harris, Dale M.; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Teo, Wei-Peng

    2015-01-01

    The use of virtual reality games (known as “exergaming”) as a neurorehabilitation tool is gaining interest. Therefore, we aim to collate evidence for the effects of exergaming on the balance and postural control of older adults and people with idiopathic Parkinson’s disease (IPD). Six electronic databases were searched, from inception to April 2015, to identify relevant studies. Standardized mean differences (SMDs) and 95% confidence intervals (CI) were used to calculate effect sizes between experimental and control groups. I2 statistics were used to determine levels of heterogeneity. 325 older adults and 56 people with IPD who were assessed across 11 ­studies. The results showed that exergaming improved static balance (SMD 1.069, 95% CI 0.563–1.576), postural control (SMD 0.826, 95% CI 0.481–1.170), and dynamic balance (SMD −0.808, 95% CI −1.192 to −0.424) in healthy older adults. Two IPD studies showed an improvement in static balance (SMD 0.124, 95% CI −0.581 to 0.828) and postural control (SMD 2.576, 95% CI 1.534–3.599). Our findings suggest that exergaming might be an appropriate therapeutic tool for improving balance and postural control in older adults, but more ­large-scale trials are needed to determine if the same is true for people with IPD. PMID:26441634

  7. Exergaming as a Viable Therapeutic Tool to Improve Static and Dynamic Balance among Older Adults and People with Idiopathic Parkinson's Disease: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Harris, Dale M; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Teo, Wei-Peng

    2015-01-01

    The use of virtual reality games (known as "exergaming") as a neurorehabilitation tool is gaining interest. Therefore, we aim to collate evidence for the effects of exergaming on the balance and postural control of older adults and people with idiopathic Parkinson's disease (IPD). Six electronic databases were searched, from inception to April 2015, to identify relevant studies. Standardized mean differences (SMDs) and 95% confidence intervals (CI) were used to calculate effect sizes between experimental and control groups. I (2) statistics were used to determine levels of heterogeneity. 325 older adults and 56 people with IPD who were assessed across 11 -studies. The results showed that exergaming improved static balance (SMD 1.069, 95% CI 0.563-1.576), postural control (SMD 0.826, 95% CI 0.481-1.170), and dynamic balance (SMD -0.808, 95% CI -1.192 to -0.424) in healthy older adults. Two IPD studies showed an improvement in static balance (SMD 0.124, 95% CI -0.581 to 0.828) and postural control (SMD 2.576, 95% CI 1.534-3.599). Our findings suggest that exergaming might be an appropriate therapeutic tool for improving balance and postural control in older adults, but more -large-scale trials are needed to determine if the same is true for people with IPD.

  8. Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit.

    Science.gov (United States)

    Miller, Larry E; Zimmermann, Angela K; Ouwehand, Arthur C

    2016-06-07

    To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) in adults and to identify factors that influence these outcomes. We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT. A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38 (95%CI: 0.23-0.53, P probiotics in subjects with vs without constipation (SMD: 0.57 vs 0.22, P probiotic strains (R (2) = 20%, P probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019 (SMD: 0.67, P probiotic strains yielded negligible reductions in ITT relative to control. Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.

  9. Contribution of defective PS recognition and efferocytosis to chronic inflammation and autoimmunity

    Directory of Open Access Journals (Sweden)

    Stanley Gititu Kimani

    2014-11-01

    Full Text Available Rapid and efficient clearance of apoptotic cells results in elimination of auto-antigens and provides a strong anti-inflammatory and immunosuppressive signal to prevent autoimmunity. While professional and non-professional phagocytes utilize a wide array of surface receptors to recognize apoptotic cells, recognition of phosphatidylserine (PS on apoptotic cells by PS receptors on phagocytes is emblematic signal for efferocytosis in metazoans. PS-dependent efferocytosis is associated with production of anti-inflammatory factors such as IL-10 and TGF-β that function, in part, to maintain tolerance to auto-antigens. In contrast, when apoptotic cells fail to be recognized and processed for degradation, auto-antigens persist, which can trigger immune activation leading to autoantibody production and autoimmunity. Despite the fact that genetic mouse models clearly demonstrate that loss of PS receptors can lead to age-dependent autoimmune diseases reminiscent of systemic lupus erythematosus (SLE, link between PS and defective clearance in chronic inflammation and human autoimmunity is not well delineated. In this hypothesis and theory, we review emerging questions developing in the field that may be of relevance to SLE and human autoimmunity.

  10. Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Mistry, Pragnesh; Kaplan, Mariana J

    2017-12-01

    Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

  11. TAM receptor knockout mice are susceptible to retinal autoimmune induction.

    Science.gov (United States)

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

    2011-06-16

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

  12. 60 kD Ro and nRNP A frequently initiate human lupus autoimmunity.

    Directory of Open Access Journals (Sweden)

    Latisha D Heinlen

    2010-03-01

    Full Text Available Systemic lupus erythematosus (SLE is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%. However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%, nRNP A (24%, anti-phospholipids (18% or rheumatoid factor (15%. We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98% or anti-52 kD Ro (95%. The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns.

  13. Endemic pemphigus over a century: Part II.

    Science.gov (United States)

    Abréu-Vélez, Ana María; Roselino, Ana Maria; Howard, Michael S; Reason, Iara J de Messias

    2010-03-01

    Endemic pemphigus foliaceus (EPF) is an autoimmune disease, classically occurring in a restricted geographic area. Foci of EPF have been described in several Central and South American countries, often affecting young people and Amerindians, with some female predilection. Although most American EPF cases have been documented in Brazil, cases have been reported in Peru, Paraguay, El Salvador and Venezuela. An additional variant of EPF has been described in El Bagre, Colombia, (El Bagre-EPF) affecting older men and a few post-menopausal females. Finally, one additional type of EPF has been described in nomadic tribes affecting females of child bearing age in Tunisia, Africa. The main aim of this review is to summarize current knowledge about autoantigens, and immunologic and genetic studies in EPF. We utilized a retrospective review of the literature, aiming to compile and compare the multiple geographic foci of EPF. The primary autoantigens in EPF are still considered to be desmogleins in the case of the Tunisian and all American cases, in contradistinction to plakins and desmogleins in El Bagre-EPF. Although several autoantigens are been suggested, their biochemical nature needs further elucidation. Current knowledge still supports the concept that an antibody mediated immune response represents the principal pathophysiology in all variants of EPF. A strong genetic susceptibility appears to contribute to disease development in several people affected by these diseases; however, no specific genes have been confirmed at present. We conclude that further investigation is necessary to define these disorders immunologically and genetically.

  14. Additive manufacturing of Ti-6Al-4V components by shaped metal deposition: Microstructure and mechanical properties

    International Nuclear Information System (INIS)

    Baufeld, Bernd; Biest, Omer Van der; Gault, Rosemary

    2010-01-01

    Shaped metal deposition (SMD) is a relatively new technology of additive manufacturing, which creates near-net shaped components by additive manufacture utilizing tungsten inert gas welding. Especially for Ti alloys, which are difficult to shape by traditional methods and for which the loss of material during machining is also very costly, SMD has great advantages. In the case of Ti-6Al-4V the dense SMD components exhibit large, columnar prior β grains, with a Widmanstaetten α/β microstructure. These prior β grains are slightly tilted in a direction following the temperature field resulting from the moving welding torch. The ultimate tensile strength is between 929 and 1014 MPa, depending on orientation and location of the tensile specimens. Tensile testing vertically to the deposition layers exhibits a strain at failure of 16 ± 3%, while testing parallel to the layers gives a lower value of about 9%.

  15. Empirical evidence of study design biases in randomized trials

    DEFF Research Database (Denmark)

    Page, Matthew J.; Higgins, Julian P. T.; Clayton, Gemma

    2016-01-01

    search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta......-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR SMD ... studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD...

  16. Impact of a daily exercise dose on knee joint cartilage

    DEFF Research Database (Denmark)

    Bricca, A; Juhl, C B; Grodzinsky, A J

    2017-01-01

    -analysis of 14 studies investigating cartilage thickness showed no effect in the low dose exercise group (SMD -0.02; 95% CI -0.42 to 0.38; I(2) = 0.0%), large but non-significant cartilage thickening in the moderate dose exercise group (SMD 0.95; 95% CI -0.33 to 2.23; I(2) = 72.1%) and non-significant cartilage...... thinning in the high dose exercise group (SMD -0.19; 95% CI -0.49 to 0.12; I(2) = 0.0%). Results were independent of analyzed covariates. The overall quality of the studies was poor because of inadequate reporting of data and high risk of bias. CONCLUSIONS: Our results suggest that the relationship between...

  17. Disagreements in meta-analyses using outcomes measured on continuous or rating scales: observer agreement study

    DEFF Research Database (Denmark)

    Tendal, Britta; Higgins, Julian P T; Jüni, Peter

    2009-01-01

    difference (SMD), the protocols for the reviews and the trial reports (n=45) were retrieved. DATA EXTRACTION: Five experienced methodologists and five PhD students independently extracted data from the trial reports for calculation of the first SMD result in each review. The observers did not have access...... to the reviews but to the protocols, where the relevant outcome was highlighted. The agreement was analysed at both trial and meta-analysis level, pairing the observers in all possible ways (45 pairs, yielding 2025 pairs of trials and 450 pairs of meta-analyses). Agreement was defined as SMDs that differed less...... than 0.1 in their point estimates or confidence intervals. RESULTS: The agreement was 53% at trial level and 31% at meta-analysis level. Including all pairs, the median disagreement was SMD=0.22 (interquartile range 0.07-0.61). The experts agreed somewhat more than the PhD students at trial level (61...

  18. Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis

    DEFF Research Database (Denmark)

    Eriksen, Patrick; Bartels, Else M; Altman, Roy D

    2014-01-01

    placebo-controlled trials was performed, and random-effects models were applied with inconsistency (I(2) ) and heterogeneity (tau(2) ) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI......)]) served as effect size. RESULTS: The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD -0.51 [95% CI -0.72, -0.30]), although a high level of between-trial inconsistency was observed (I(2) = 88%). The single most important explanation (i.e., covariate......) was brand, reducing heterogeneity by 41% (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD -1.07 [95% CI -1.47, -0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less...

  19. The Effectiveness of Aromatherapy in Reducing Pain: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Sheafer, Heather; Tepper, Deborah

    2016-01-01

    Background. Aromatherapy refers to the medicinal or therapeutic use of essential oils absorbed through the skin or olfactory system. Recent literature has examined the effectiveness of aromatherapy in treating pain. Methods. 12 studies examining the use of aromatherapy for pain management were identified through an electronic database search. A meta-analysis was performed to determine the effects of aromatherapy on pain. Results. There is a significant positive effect of aromatherapy (compared to placebo or treatments as usual controls) in reducing pain reported on a visual analog scale (SMD = −1.18, 95% CI: −1.33, −1.03; p aromatherapy is more consistent for treating nociceptive (SMD = −1.57, 95% CI: −1.76, −1.39, p aromatherapy is most effective in treating postoperative pain (SMD = −1.79, 95% CI: −2.08, −1.51, p aromatherapy can successfully treat pain when combined with conventional treatments. PMID:28070420

  20. Toll-like receptor 3 stimulation promotes Ro52/TRIM21 synthesis and nuclear redistribution in salivary gland epithelial cells, partially via type I interferon pathway

    Science.gov (United States)

    Kyriakidis, N C; Kapsogeorgou, E K; Gourzi, V C; Konsta, O D; Baltatzis, G E; Tzioufas, A G

    2014-01-01

    Up-regulated expression of Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2) and lupus LA protein/Sjögren's syndrome antigen B (La/SSB) autoantigens has been described in the salivary gland epithelial cells (SGEC) of patients with Sjögren's syndrome (SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional Toll-like receptor (TLR)-3, whereas Ro52/TRIM21 negatively regulates TLR-3-mediated inflammation. Herein, we investigated the effect of TLR-3-signalling on the expression of Ro52/TRIM21, as well as Ro60/TROVE2 and La/SSB autoantigens, by SGECs. The effect of TLR-3 or TLR-4 stimulation on autoantigen expression was evaluated by polyI:C or lipopolysaccharide (LPS) treatment, respectively, of SGEC lines (10 from SS patients, 12 from non-SS controls) or HeLa cells, followed by analysis of mRNA and protein expression. PolyI:C, but not LPS, resulted in a two-step induction of Ro52/TRIM21 mRNA expression by SGECs, a 12-fold increment at 6 h followed by a 2·5-fold increment at 24–48 h, whereas it induced a late two-fold up-regulation of Ro60/TROVE2 and La/SSB mRNAs at 48 h. Although protein expression levels were not affected significantly, the late up-regulation of Ro52/TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout the nucleus. These late phenomena were mediated significantly by interferon (IFN)-β production, as attested by cognate secretion and specific inhibition experiments and associated with IFN regulatory factor (IRF)3 degradation. TLR-3-signalling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells. TLR-3 signalling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their over-expression in inflamed tissues and possibly in their exposure to the immune

  1. A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I).

    Science.gov (United States)

    Reddy, Varikasuvu Seshadri; Bukke, Suman; Dutt, Naveen; Rana, Puneet; Pandey, Arun Kumar

    2017-07-01

    Available studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. The objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. All major databases were searched for eligible studies. We included 12 case-control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. Random-effects meta-analysis indicated a decrease in circulatory (SMD=-0.44), erythrocellular (SMD=-0.52) and CSF (SMD=-0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=-0.55) and without (SMD=-0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. This meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Effectiveness of Aquatic Exercise in Improving Lower Limb Strength in Musculoskeletal Conditions: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Heywood, Sophie; McClelland, Jodie; Mentiplay, Benjamin; Geigle, Paula; Rahmann, Ann; Clark, Ross

    2017-01-01

    To investigate the effectiveness of aquatic exercise in improving lower limb strength in people with musculoskeletal conditions. A systematic search used 5 databases, including MEDLINE, CINAHL, Embase, SPORTDiscus, and The Cochrane Library. Randomized controlled trials evaluating aquatic exercise with a resistance training component for adults with musculoskeletal conditions compared with no intervention or land-based exercise were identified. Fifteen studies from the initial yield of 1214 met these criteria. Data related to participant demographics, study design, and methods, interventions, and outcomes, including numerical means and SDs, were extracted independently by 2 reviewers. Nine of the 15 studies were of high quality, scoring at least 6 on the Physiotherapy Evidence Database Scale. Limited consideration of the prescription of resistance in the aquatic exercise and application of resistance training principles existed. Low- or very low-quality evidence indicates there was no difference in average effect between aquatic exercise and no exercise in improving hip abductor strength (standardized mean difference [SMD], .28; 95% confidence interval [CI], -.04 to .59), knee extensor strength (SMD, .18; 95% CI, -.03 to .40), knee flexor strength (SMD, .13; 95% CI, -.20 to .45), or lower limb endurance (SMD, .35; 95% CI, -.06 to .77). Low-quality evidence indicates no difference in average effect between aquatic and land exercise for knee extensor (SMD, -.24; 95% CI, -.49 to .02) or flexor strength (SMD, -.15; 95% CI, -.53 to .22). It is likely that the inadequate application of resistance in water is a significant contributor to the limited effectiveness of aquatic exercise interventions in improving hip and knee muscle strength in people with musculoskeletal conditions. Future research is needed to quantify resistance with aquatic exercises and to determine if using opportunities for greater resistance in aquatic rehabilitation and appropriate resistance

  3. Eating attentively: a systematic review and meta-analysis of the effect of food intake memory and awareness on eating1234

    Science.gov (United States)

    Aveyard, Paul; Daley, Amanda; Jolly, Kate; Lewis, Amanda; Lycett, Deborah; Higgs, Suzanne

    2013-01-01

    Background: Cognitive processes such as attention and memory may influence food intake, but the degree to which they do is unclear. Objective: The objective was to examine whether such cognitive processes influence the amount of food eaten either immediately or in subsequent meals. Design: We systematically reviewed studies that examined experimentally the effect that manipulating memory, distraction, awareness, or attention has on food intake. We combined studies by using inverse variance meta-analysis, calculating the standardized mean difference (SMD) in food intake between experimental and control groups and assessing heterogeneity with the I2 statistic. Results: Twenty-four studies were reviewed. Evidence indicated that eating when distracted produced a moderate increase in immediate intake (SMD: 0.39; 95% CI: 0.25, 0.53) but increased later intake to a greater extent (SMD: 0.76; 95% CI: 0.45, 1.07). The effect of distraction on immediate intake appeared to be independent of dietary restraint. Enhancing memory of food consumed reduced later intake (SMD: 0.40; 95% CI: 0.12, 0.68), but this effect may depend on the degree of the participants’ tendencies toward disinhibited eating. Removing visual information about the amount of food eaten during a meal increased immediate intake (SMD: 0.48; 95% CI: 0.27, 0.68). Enhancing awareness of food being eaten may not affect immediate intake (SMD: 0.09; 95% CI: −0.42, 0.35). Conclusions: Evidence indicates that attentive eating is likely to influence food intake, and incorporation of attentive-eating principles into interventions provides a novel approach to aid weight loss and maintenance without the need for conscious calorie counting. PMID:23446890

  4. Inflammatory Markers and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Bin Su

    Full Text Available Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD. We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD. Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015. A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations. Sensitivity analyses for publication bias were performed. We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls. Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92-1.50; P < 0.001, leukocytes (SMD: 1.07; 95%: 0.25-1.88; P = 0.010, IL-6 (SMD: 0.90; 95%CI: 0.48-1.31; P < 0.001, IL-8 (SMD: 2.34; 95%CI: 0.69-4.00; P = 0.006, and fibrinogen levels (SMD: 0.87; 95%CI: 0.44-1.31; P < 0.001 when compared with control. However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266. Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α.

  5. A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity.

    Science.gov (United States)

    Beserra, Bruna T S; Fernandes, Ricardo; do Rosario, Vinicius A; Mocellin, Michel C; Kuntz, Marilyn G F; Trindade, Erasmo B S M

    2015-10-01

    Several studies have reported the effects of prebiotics and synbiotics supplementation in lipid profile and glucose homeostasis, however a pooled analysis of clinical trials that assessed these parameters has not been performed in overweight or obese individuals. The aim of this study was to evaluate the effects of prebiotics and synbiotics on plasma lipid profile, fasting insulin and fasting glucose in adults with overweight or obesity. Randomized controlled trials were systematically searched before May 2014 in electronic databases and screening reference lists. Combined and stratified (diabetics and non-diabetics trials) meta-analyzes were performed. Thirteen trials, representing 513 adult participants with Body Mass Index ≥25 kg/m² were included. Prebiotic supplementation reduced plasma total cholesterol (SMD -0.25; 95% CI -0.48, -0.02) and LDL-c (SMD -0.22; 95% CI -0.44, -0.00) concentrations in overall analysis, and reduced triglycerides (SMD -0.72; 95% CI -1.20, -0.23) and increased HDL-c (SMD 0.49; 95% CI 0.01, 0.97) concentrations in diabetic trials. Synbiotic supplementation reduced plasma fasting insulin (SMD -0.39; 95% CI -0.75, -0.02) and triglycerides (SMD -0.43; 95% CI -0.70, -0.15) concentrations. The improvement of the evaluated parameters supports prebiotics and synbiotics supplementation as an adjuvant therapy in obesity-related comorbidities, such as dyslipidemia and insulin resistance. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  6. Using the system maintenance datastore to characterize lifetime maintenance for PLiM

    International Nuclear Information System (INIS)

    Watson, P.; Dam, R.; Nickerson, J.

    2004-01-01

    A comprehensive Plant Life Management (PLiM) program involves evaluating a large amount of information. For any plant, there are numerous maintenance, surveillance and inspection programs for the important systems, structures and components. There is extensive industry experience on component failure modes, degradation mechanisms and recommended maintenance practices. This information forms the basis of the aging assessment work, through which improvements to these plant programs are identified. AECL has developed several tools to manage the quantities of information required in aging assessment studies, such as the SYSTMS (SYtematic approach for the development of STrategy for Maintenance and Surveillance) tool and the System Maintenance Datastore (SMD). The SMD has been developed to serve as a hub to a Systematic based Adaptive Maintenance Program (SAMP), by storing maintenance resource requirements for recommended maintenance tasks for use by the other processes in a SAMP. The SMD can be used to (a) quantify the savings or cost of optimising a maintenance program, (b) characterize and understand long term trends in condition-based maintenance due to component aging, (c) quantify the resource savings due to optimum timing of component replacement or general plant refurbishment, and (d) provide aging assessment cost information for input to plant asset evaluation. The SMD contains data for regular maintenance program tasks, plant condition assessment recommendations, and equipment refurbishment costs. A prototype SMD has been developed with data tables populated with information from operating CANDU stations. The SMD is now available to be used either with a SYSTMS evaluation or with a plant's database of maintenance tasks. (author)

  7. Physical activity interventions for people with mental illness: a systematic review and meta-analysis.

    Science.gov (United States)

    Rosenbaum, Simon; Tiedemann, Anne; Sherrington, Catherine; Curtis, Jackie; Ward, Philip B

    2014-09-01

    To determine effects of physical activity on depressive symptoms (primary objective), symptoms of schizophrenia, anthropometric measures, aerobic capacity, and quality of life (secondary objectives) in people with mental illness and explore between-study heterogeneity. MEDLINE, Cochrane Controlled Trials Register, PsycINFO, CINAHL, Embase, and the Physiotherapy Evidence Database (PEDro) were searched from earliest record to 2013. Randomized controlled trials of adults with a DSM-IV-TR, ICD-10, or clinician-confirmed diagnosis of a mental illness other than dysthymia or eating disorders were selected. Interventions included exercise programs, exercise counseling, lifestyle interventions, tai chi, or physical yoga. Study methodological quality and intervention compliance with American College of Sports Medicine (ACSM) guidelines were also assessed. Two investigators extracted data. Data were pooled using random-effects meta-analysis. Meta-regression was used to examine sources of between-study heterogeneity. Thirty-nine eligible trials were identified. The primary meta-analysis found a large effect of physical activity on depressive symptoms (n = 20; standardized mean difference (SMD) = 0.80). The effect size in trial interventions that met ACSM guidelines for aerobic exercise did not differ significantly from those that did not meet these guidelines. The effect for trials with higher methodological quality was smaller than that observed for trials with lower methodological quality (SMD = 0.39 vs 1.35); however, the difference was not statistically significant. A large effect was found for schizophrenia symptoms (SMD = 1.0), a small effect was found for anthropometry (SMD = 0.24), and moderate effects were found for aerobic capacity (SMD = 0.63) and quality of life (SMD = 0.64). Physical activity reduced depressive symptoms in people with mental illness. Larger effects were seen in studies of poorer methodological quality. Physical activity reduced symptoms of

  8. Eating attentively: a systematic review and meta-analysis of the effect of food intake memory and awareness on eating.

    Science.gov (United States)

    Robinson, Eric; Aveyard, Paul; Daley, Amanda; Jolly, Kate; Lewis, Amanda; Lycett, Deborah; Higgs, Suzanne

    2013-04-01

    Cognitive processes such as attention and memory may influence food intake, but the degree to which they do is unclear. The objective was to examine whether such cognitive processes influence the amount of food eaten either immediately or in subsequent meals. We systematically reviewed studies that examined experimentally the effect that manipulating memory, distraction, awareness, or attention has on food intake. We combined studies by using inverse variance meta-analysis, calculating the standardized mean difference (SMD) in food intake between experimental and control groups and assessing heterogeneity with the I(2) statistic. Twenty-four studies were reviewed. Evidence indicated that eating when distracted produced a moderate increase in immediate intake (SMD: 0.39; 95% CI: 0.25, 0.53) but increased later intake to a greater extent (SMD: 0.76; 95% CI: 0.45, 1.07). The effect of distraction on immediate intake appeared to be independent of dietary restraint. Enhancing memory of food consumed reduced later intake (SMD: 0.40; 95% CI: 0.12, 0.68), but this effect may depend on the degree of the participants' tendencies toward disinhibited eating. Removing visual information about the amount of food eaten during a meal increased immediate intake (SMD: 0.48; 95% CI: 0.27, 0.68). Enhancing awareness of food being eaten may not affect immediate intake (SMD: 0.09; 95% CI: -0.42, 0.35). Evidence indicates that attentive eating is likely to influence food intake, and incorporation of attentive-eating principles into interventions provides a novel approach to aid weight loss and maintenance without the need for conscious calorie counting.

  9. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients.

    Science.gov (United States)

    Machado, Mariana V; Oliveira, António G; Cortez-Pinto, Helena

    2011-09-01

    Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a meta-analysis to evaluate HS prevalence and risk factors, in HBV infection. Standard guidelines for performance of meta-analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random-effects model and DerSimonian-Laid method. Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI [0.45-0.67], P SMD 2.17, 95%CI [1.23, 3.11], P SMD 0.84, 95%CI [0.00, 1.67], P = 0.049), triglycerides (SMD 1.18, 95%CI [0.48, 1.89], P = 0.001), cholesterol (SMD 0.88, 95%CI [0.31, 1.45], P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI [1.10-2.15], P = 0.011) and negatively with HBV DNA (SMD -74.12, 95%CI [-82.93, -65.31], P infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  10. A Systematic Review and Meta-Analysis of Baduanjin Qigong for Health Benefits: Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Liye Zou

    2017-01-01

    Full Text Available Objective. To investigate the effects of practicing Baduanjin Qigong on different health outcomes. Methods. Six electronic databases were used for literature search through entering the following key words: Baduanjin Qigong, quality of life, sleep quality, and health-related outcomes. Results. Nineteen randomized controlled trials were used for meta-analysis. The aggregated results from this systematic review have shown significant benefits in favour of Baduanjin Qigong on quality of life (SMD, −0.75; 95% CI −1.26 to −0.24; P=0.004, sleep quality (SMD, −0.55; 95% CI −0.97 to −0.12; P=0.01, balance (SMD, −0.94; 95% CI −1.59 to 0.30; P=0.004, handgrip strength (SMD, -0.69; 95% CI −1.2 to −0.19; P=0.007, trunk flexibility (SMD, −0.66; 95% CI −1.13 to −0.19; P=0.006, systolic (SMD, −0.60; 95% CI −0.94 to −0.27; P=0.0004 and diastolic blood pressure (SMD, −0.46; 95% CI −0.73 to −0.20; P=0.0005, and resting heart rate (SMD, −0.87; 95% CI −1.47 to −0.27; P=0.005. The aggregated results of meta-analyses examining the effect of Baduanjin Qigong on leg power, cardiopulmonary endurance, and pulmonary function remain unclear because of a small number of studies. Conclusions. The aggregated results from this systematic review show that Baduanjin Qigong practice is beneficial for quality of life, sleep quality, balance, handgrip strength, trunk flexibility, systolic and diastolic blood pressure, and resting heart rate. Further studies are necessary to confirm the effects of Baduanjin Qigong on leg power, cardiopulmonary endurance, and pulmonary function (e.g., vital capacity, while considering a long-term follow-up. Registration Number. This trial is registered with International Prospective Register of Systematic Reviews (PROSPERO: CRD42016036966.

  11. Soft and Hard Tissue Changes Following Immediate Placement or Immediate Restoration of Single-Tooth Implants in the Esthetic Zone: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Yan, Qi; Xiao, Li-Qun; Su, Mei-Ying; Mei, Yan; Shi, Bin

    This systematic review aimed to compare immediate protocols with conventional protocols of single-tooth implants in terms of changes in the surrounding hard and soft tissue in the esthetic area. Electronic and manual searches were performed in PubMed, EMBASE, Cochrane, and other data systems for research articles published between January 2001 and December 2014. Only randomized controlled trials (RCTs) reporting on hard and or soft tissue characteristics following a single-tooth implant were included. Based on the protocol used in each study, the included studies were categorized into three groups to assess the relationships between the factors and related esthetic indexes. Variables such as marginal bone level changes (mesial, distal, and mean bone level), peri-implant soft tissue changes (papilla level, midbuccal mucosa, and probing depth), and other esthetic indices were taken into consideration. The data were analyzed using RevMan version 5.3, Stata 12, and GRADEpro 3.6.1 software. A total of 13 RCTs met the inclusion criteria. Four studies examined immediate implant placement, five studies examined immediate implant restoration, and four studies examined immediate loading. Comparing the bone level changes following immediate and conventional restoration, no significant differences were found in the bone level of the mesial site (standard mean difference [SMD] = -0.04 mm; 95% confidence interval [CI]: -0.25 to 0.17 mm), the distal site (SMD = -0.15 mm; 95% CI: -0.38 to 0.09 mm), and the mean bone level changes (SMD = 0.05 mm; 95% CI: -0.18 to 0.27 mm). The difference in the marginal bone level changes between immediate and conventional loading was also not statistically significant (SMD = -0.05 mm; 95% CI: -0.15 to 0.06 mm for the mesial site and SMD = -0.02 mm; 95% CI: -0.09 to 0.05 mm for the distal site). Soft tissue changes following immediate and conventional restoration reported no significant differences in the papillae level of the mesial site (SMD = 0

  12. The Intersection of NASA Astrophysics Education and Public Outreach and Higher Education: A Special Interest Group Meeting

    Science.gov (United States)

    Sharma, M.; Smith, D.; Schultz, G.; Bianchi, L.; Blair, W.

    2011-09-01

    This paper presents highlights from a group discussion on how the NASA Science Mission Directorate (SMD) education and public outreach (EPO) community could better support undergraduate astronomy education through EPO products and resources - current and future - targeted at the college level. The discussion was organized by the SMD Astrophysics EPO Forum through a Special Interest Group Meeting at the 2010 ASP Annual Meeting in Boulder. Our session took advantage of the simultaneous presence of EPO professionals and the Cosmos in the Classroom participants to seek out diverse perspectives on and experiences in higher education.

  13. The Frequency of Serous Macular Detachment in Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Onur Yaya

    2015-05-01

    Full Text Available Objectives: To investigate the epidemiology and frequency of serous macular detachment (SMD in patients diagnosed with diabetic macular edema (DME. Materials and Methods: Hundred and forty-three eyes of 104 patients with DME were examined retrospectively. According to the results of OCT, the patients were separated into two groups; patients diagnosed with SMD and DME (group 1 and patients diagnosed with DME (group 2. They were assessed based on demographic characteristics, average age, duration of diabetes mellitus (DM, hypertension (HT history, best-corrected visual acuity, and diabetic retinopathy stages. Results: The average age of the patients was 61±8.7 years. Forty-three patients (41.3% were female and 61 patients (58.7% were male. Fifty-four of 104 patients (51.9% had DME with SMD. 21 (38.8% patients had bilateral SMD. In group 1, 31 patients were male (57.4% and 23 patients were female (42.6%. In group 2, 30 (60% patients were male and 20 (40% patients were female. In group 1, average age was 60.2±9.6 and the average duration of DM was 12.2±7.0 years, whereas the average age was 61.9±7.6 and the average duration of DM was 14.06±6.8 years in group 2. Forty-two patients in group 1 (77.8% and 30 patients (60% in group 2 had history of HT. Before the treatment, the average best-corrected visual acuity was found to be 0.30±0.24 in group 1 and 0.32±0.25 in group 2. Conclusion: Today, it is thought that diabetic maculopathy is the leading cause of SMD and it is a determining factor of treatment applications. In our study, we aimed at investigating the frequency of SMD in DME and the risk factors for the development of SMD. Although there were some differences between the factors, only the history of HT was found statistically higher in patients with SMD (p=0.04. (Turk J Ophthalmol 2015; 45: 92-96

  14. Tai Chi for Chronic Pain Conditions: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Kong, Ling Jun; Lauche, Romy; Klose, Petra; Bu, Jiang Hui; Yang, Xiao Cun; Guo, Chao Qing; Dobos, Gustav; Cheng, Ying Wu

    2016-04-29

    Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD], -0.54; 95% confidence intervals [CI], -0.77 to -0.30; P chronic pain from low back pain (SMD, -0.81; 95% CI, -1.11 to -0.52; P complementary and alternative medicine for chronic pain conditions.

  15. Effectiveness of conservative interventions including exercise, manual therapy and medical management in adults with shoulder impingement: a systematic review and meta-analysis of RCTs.

    Science.gov (United States)

    Steuri, Ruedi; Sattelmayer, Martin; Elsig, Simone; Kolly, Chloé; Tal, Amir; Taeymans, Jan; Hilfiker, Roger

    2017-09-01

    To investigate the effectiveness of conservative interventions for pain, function and range of motion in adults with shoulder impingement. Systematic review and meta-analysis of randomised trials. Medline, CENTRAL, CINAHL, Embase and PEDro were searched from inception to January 2017. Randomised controlled trials including participants with shoulder impingement and evaluating at least one conservative intervention against sham or other treatments. For pain, exercise was superior to non-exercise control interventions (standardised mean difference (SMD) -0.94, 95% CI -1.69 to -0.19). Specific exercises were superior to generic exercises (SMD -0.65, 95% CI -0.99 to -0.32). Corticosteroid injections were superior to no treatment (SMD -0.65, 95% CI -1.04 to -0.26), and ultrasound guided injections were superior to non-guided injections (SMD -0.51, 95% CI -0.89 to -0.13). Nonsteroidal anti-inflammatory drugs (NSAIDS) had a small to moderate SMD of -0.29 (95% CI -0.53 to -0.05) compared with placebo. Manual therapy was superior to placebo (SMD -0.35, 95% CI -0.69 to -0.01). When combined with exercise, manual therapy was superior to exercise alone, but only at the shortest follow-up (SMD -0.32, 95% CI -0.62 to -0.01). Laser was superior to sham laser (SMD -0.88, 95% CI -1.48 to -0.27). Extracorporeal shockwave therapy (ECSWT) was superior to sham (-0.39, 95% CI -0.78 to -0.01) and tape was superior to sham (-0.64, 95% CI -1.16 to -0.12), with small to moderate SMDs. Although there was only very low quality evidence, exercise should be considered for patients with shoulder impingement symptoms and tape, ECSWT, laser or manual therapy might be added. NSAIDS and corticosteroids are superior to placebo, but it is unclear how these treatments compare to exercise. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Soil-transmitted helminth infection, loss of education and cognitive impairment in school-aged children: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Noel Pabalan

    2018-01-01

    Full Text Available Evidence of an adverse influence of soil transmitted helminth (STH infections on cognitive function and educational loss is equivocal. Prior meta-analyses have focused on randomized controlled trials only and have not sufficiently explored the potential for disparate influence of STH infection by cognitive domain. We re-examine the hypothesis that STH infection is associated with cognitive deficit and educational loss using data from all primary epidemiologic studies published between 1992 and 2016.Medline, Biosis and Web of Science were searched for original studies published in the English language. Cognitive function was defined in four domains (learning, memory, reaction time and innate intelligence and educational loss in two domains (attendance and scholastic achievement. Pooled effect across studies were calculated as standardized mean differences (SMD to compare cognitive and educational measures for STH infected/non-dewormed children versus STH uninfected /dewormed children using Review Manager 5.3. Sub-group analyses were implemented by study design, risk of bias (ROB and co-prevalence of Schistosoma species infection. Influential studies were excluded in sensitivity analysis to examine stability of pooled estimates.We included 36 studies of 12,920 children. STH infected/non-dewormed children had small to moderate deficits in three domains-learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01-0.03 compared to STH-uninfected/dewormed children. There were no differences by infection/treatment status for reaction time, school attendance and scholastic achievement (SMD: -0.26 to -0.16, P = 0.06-0.19. Heterogeneity of the pooled effects in all six domains was high (P<0.01; I2 = 66-99%. Application of outlier treatment reduced heterogeneity in learning domain (P = 0.12; I2 = 33% and strengthened STH-related associations in all domains but intelligence (SMD: -0.20, P = 0.09. Results varied by study design and ROB. Among experimental

  17. Excess mortality in persons with severe mental disorders

    DEFF Research Database (Denmark)

    Liu, Nancy H; Daumit, Gail L; Dua, Tarun

    2017-01-01

    Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base...

  18. Low dimensional temporal organization of spontaneous eye blinks in adults with developmental disabilities and stereotyped movement disorder.

    Science.gov (United States)

    Lee, Mei-Hua; Bodfish, James W; Lewis, Mark H; Newell, Karl M

    2010-01-01

    This study investigated the mean rate and time-dependent sequential organization of spontaneous eye blinks in adults with intellectual and developmental disability (IDD) and individuals from this group who were additionally categorized with stereotypic movement disorder (IDD+SMD). The mean blink rate was lower in the IDD+SMD group than the IDD group and both of these groups had a lower blink rate than a contrast group of healthy adults. In the IDD group the n to n+1 sequential organization over time of the eye-blink durations showed a stronger compensatory organization than the contrast group suggesting decreased complexity/dimensionality of eye-blink behavior. Very low blink rate (and thus insufficient time series data) precluded analysis of time-dependent sequential properties in the IDD+SMD group. These findings support the hypothesis that both IDD and SMD are associated with a reduction in the dimension and adaptability of movement behavior and that this may serve as a risk factor for the expression of abnormal movements.

  19. Funding and Strategic Alignment Guidance for Infusing Small Business Innovation Research Technology Into Science Mission Directorate Projects at Glenn Research Center for 2015

    Science.gov (United States)

    Nguyen, Hung D.; Steele, Gynelle C.

    2016-01-01

    This report is intended to help NASA program and project managers incorporate Glenn ResearchCenter Small Business Innovation Research/Small Business Technology Transfer (SBIR)/(STTR)technologies into NASA Science Mission Directorate (SMD) programs/projects. Other Government and commercial project managers can also find this useful.

  20. Estimation of the sauter mean diameter for biodiesels by the mixture topological index

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Qing; Gao, Jixian; Liao, Yuhui; Wang, Dezheng; Wang, Jinfu [Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology, Department of Chemical Engineering, Tsinghua University, Beijing 100084 (China)

    2011-02-15

    A pure component topological index was integrated with the modified Grunberg-Nissan or the modified Dalton-type mass-average equation to calculate the mean topological index {chi}{sub m,1} or {chi}{sub m,2} of five biodiesel fuels (peanut, canola, coconut, and palm, soybean oil). Then, the {chi}{sub m,1} or {chi}{sub m,2} was respectively related with the SMD values of biodiesel fuels (taken from the literature, at 313 K), and two regression equations were obtained. The regression equation derived from {chi}{sub m,1} has a higher predictive accuracy than the regression equation derived from {chi}{sub m,2}, and the deviations of these two regression equations were within 1.73% and 1.87%, respectively. Furthermore, a regression equation derived from the correlation of {chi}{sub m,1} and SMD was used to calculate the SMD values of biodiesel fuels (at 353 K), and the deviations were within 0.78%. Three types of hypothetical biodiesel fuels were investigated to know the effect of the molecular structure (carbon number and unsaturated bond) on the SMD. A suitable material for the preparation of a biodiesel having the comparable atomization with the diesel no.1 or no.2 will be composed of such components (low carbon number and more unsaturated bonds). (author)

  1. Static Memory Deduplication for Performance Optimization in Cloud Computing

    Directory of Open Access Journals (Sweden)

    Gangyong Jia

    2017-04-01

    Full Text Available In a cloud computing environment, the number of virtual machines (VMs on a single physical server and the number of applications running on each VM are continuously growing. This has led to an enormous increase in the demand of memory capacity and subsequent increase in the energy consumption in the cloud. Lack of enough memory has become a major bottleneck for scalability and performance of virtualization interfaces in cloud computing. To address this problem, memory deduplication techniques which reduce memory demand through page sharing are being adopted. However, such techniques suffer from overheads in terms of number of online comparisons required for the memory deduplication. In this paper, we propose a static memory deduplication (SMD technique which can reduce memory capacity requirement and provide performance optimization in cloud computing. The main innovation of SMD is that the process of page detection is performed offline, thus potentially reducing the performance cost, especially in terms of response time. In SMD, page comparisons are restricted to the code segment, which has the highest shared content. Our experimental results show that SMD efficiently reduces memory capacity requirement and improves performance. We demonstrate that, compared to other approaches, the cost in terms of the response time is negligible.

  2. ON THE INCONSISTENCY BETWEEN COSMIC STELLAR MASS DENSITY AND STAR FORMATION RATE UP TO z ∼ 8

    International Nuclear Information System (INIS)

    Yu, H.; Wang, F. Y.

    2016-01-01

    In this paper, we test the discrepancy between the stellar mass density (SMD) and instantaneous star formation rate in the redshift range 0 < z < 8 using a large observational data sample. We first compile the measurements of SMDs up to z ∼ 8. Comparing the observed SMDs with the time-integral of instantaneous star formation history (SFH), we find that the observed SMDs are lower than that implied from the SFH at z < 4. We also use the Markov chain Monte Carlo (MCMC) method to derive the best-fitting SFH from the observed SMD data. At 0.5 < z < 6, the observed star formation rate densities are larger than the best-fitting one, especially at z ∼ 2 where they are larger by a factor of about two. However, at lower (z < 0.5) and higher redshifts (z > 6), the derived SFH is consistent with the observations. This is the first time that the discrepancy between the observed SMD and instantaneous star formation rate has been tested up to very high redshift z ≈ 8 using the MCMC method and a varying recycling factor. Several possible reasons for this discrepancy are discussed, such as underestimation of SMD, initial mass function, and evolution of cosmic metallicity

  3. Pediatric Bipolar Disorder versus Severe Mood Dysregulation: Risk for Manic Episodes on Follow-Up

    Science.gov (United States)

    Stringaris, Argyris; Baroni, Argelinda; Haimm, Caroline; Brotman, Melissa; Lowe, Catherine H.; Myers, Frances; Rustgi, Eileen; Wheeler, Wanda; Kayser, Reilly; Towbin, Kenneth; Leibenluft, Ellen

    2010-01-01

    Objective: An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be…

  4. [Cardiovascular risk factors in users with severe mental disorder].

    Science.gov (United States)

    Paños-Martínez, Montserrat; Patró-Moncunill, Ester; Santiago-Barragán, Ángel-María; Marti-Mestre, Marc; Torralbas-Ortega, Jordi; Escayola-Maranges, Anna; Granero-Lázaro, Alberto

    2016-01-01

    To identify the prevalence of the cardiovascular risk (RCV) in users with a Severe Mental Disorder (SMD) attended in mental health service in ParcTaulí (Sabadell - Barcelona). This is an observational, descriptive and transversal study of the factors of cardiovascular risk in 789 users with SMD. The instrument used was the scale of assessment of the Registre Gironí del Cor, which estimates the risk of cardiovascular disease. 26.6% of the sample has RCV (22.5% moderate, 3.8% high and 0.3% very high). The analysis of the modifiable risk factors shows that 16.5% of the patients are hypertensive, 55.2% are smokers, 19.77% have hyperglycaemia (8.2% of whom are diagnosed of diabetes mellitus), 40.2% have obesity, 36.2% overweight and 47.27% hypercholesterolemia. The study confirms that the prevalence of the RVC in SMD users is greater than the RCV in general population and it's associated to the presence of modifiable risk factors. Health education carried out by nurses is the best to prevent the RCV in SMD users. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  5. 76 FR 7864 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Science.gov (United States)

    2011-02-11

    ...: Psychiatric Unit Criteria Work Sheet and Supporting Regulations 412.25 and 412.27; Use: A limited number of... National Correct Coding Initiative in Medicaid, SMD Letter 10-017 dated September 1, 2010. Use; The Patient... State Use of National Correct Coding Initiative. A State Medicaid Director letter, 10-017 dated...

  6. Treatment effectiveness and fidelity of manual therapy to the knee: A systematic review and meta-analysis.

    Science.gov (United States)

    Salamh, Paul; Cook, Chad; Reiman, Michael P; Sheets, Charles

    2017-09-01

    Manual therapy (MT) is a commonly used treatment for knee osteoarthritis (OA) but to date only one systematic review has explored its effectiveness. The purpos e of the present study was to perform a systematic review and meta-analysis of the literature, to determine the effectiveness and fidelity of studies using MT techniques in individuals with knee OA. Relevant studies were assessed for inclusion. Effectiveness was measured using effect sizes, and methodological bias and treatment fidelity were both explored. Effect sizes were calculated using standardized mean differences (SMD) based on pooled data depending on statistical and clinical heterogeneity, as well as risk of bias. The search captured 2,969 studies; after screening, 12 were included. Four had a low risk of bias and high treatment fidelity. For self-reported function, comparing MT with no treatment resulted in a large effect size (standardized mean difference [SMD] 0.84), as did adding MT to a comparator treatment (SMD 0.78). A significant difference was found for pain when adding MT to a comparator treatment (SMD 0.73). The findings in the present meta-analytical review support the use of MT versus a number of different comparators for improvement in self-reported knee function. Lesser support is present for pain reduction, and no endorsement of functional performance can be made at this time. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Enzymatic studies on planar supported membranes using a widefield fluorescence LAURDAN Generalized Polarization imaging approach

    DEFF Research Database (Denmark)

    Brewer, Jonathan R.; Thoke, Henrik Seir; Stock, Robeto

    2017-01-01

    studied structural and dynamical transformations induced by Sphingomyelinase D (SM-D) on planar supported membranes composed of N-lauroyl sphingomyelin (C12SM). GP data show the evolution of an initially compositionally homogeneous symmetric bilayer existing in a single liquid disordered phase...

  8. The influence of atomizer internal design and liquid physical properties on effervescent atomizing of coal-water slurry

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Meng; Duan, Yufeng [Southeast Univ., Nanjing (China). Inst. of Thermal Engineering

    2013-07-01

    This study investigated the dependence of effervescent atomizing of coal-water slurry (CWS) on atomizer internal design and fluid properties. Results demonstrate that internal design of atomizer and fluid properties directly affect the two-phase flow pattern inside the atomizer which consequently affects the spray quality. The influence of mixing chamber length on spray quality is not significant at the ALR of 0.15 except for spray 0.75 glycerol/0.248 water/0.002 xanthan mixture. The same trend also found in the effect of angle of aeration holes at ALR of 0.15. Large diameter of the inclined aeration holes shows small SMD for water. The consistency index of fluids has no effect on the spray quality and Sauter Mean Diameter (SMD) increases when polymer additions were added to the glycerin-water mixture. The radial profile of SMD for spray water are almost flat, however, the largest SMD can be obtained at the edge of spray for three other fluids.

  9. WITHDRAWN

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Lund, Søren S; Gluud, Christian

    2015-01-01

    intervals (CI). Health-related quality of life and costs of intervention were assessed with standardized mean differences (SMD) and 95% Cl. MAIN RESULTS: Twenty-eight trials with 34,912 T2D participants randomised 18,717 participants to intensive glycaemic control versus 16,195 participants to conventional...

  10. Computational and Experimental Study of Bubble Size in Bubble Columns

    DEFF Research Database (Denmark)

    Hansen, Rolf

    sammenklumpning og opbrydning af bobler, hvorved en Sauter gennemsnitsdiameter (SMD) beregnes i domænet. Boblestørrelsesfordelingen måles i en kvadratisk boblekolonne med ”Interferometric Particle Imaging” (IPI), som er en ikke-indtrængende optisk laserbaseret metode. Boblehastigheden måles samtidig med ”Particle...... Tracking Velocimetry” (PTV). Målingerne udføres for tre superficielle gashastigheder i en plan i midten af boblekolonnen. IPImålingerne viser en SMD på omkring 6.0mm for hele måleområdet, hvilket også er observeret visuelt. Lokale boblestørrelseshistogrammer præsenteres for at få data, der kan sammenlignes...... med beregningerne. Den eksperimentelle SMD synes at være konstant lodret gennem boblekolonnen, men faldende fra midten ind mod væggen horisontalt. Den eksperimentelle SMD synes også at falde med stigende superficiel gashastighed.  En beregningsanalyse af flowmønstret i den kvadratiske boblekolonne er...

  11. Motiverende mobilteknologi i skole-hjemsamarbejde

    DEFF Research Database (Denmark)

    Sønnichsen, Lise Hostrup

    2016-01-01

    Artikel handler om, hvordan brugen af en handicapkompenserende applikation ShowMyDay (SMD) kan betyde en kvalitativ forskel i skole-hjem-samarbejdet omkring elever med ASF og lignende vanskeligheder. Derudover giver artiklen i et implementeringsperspektiv et bud på forudsætningerne herfor ved...

  12. Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort

    DEFF Research Database (Denmark)

    O'Gorman, A; Suvitaival, T; Ahonen, L

    2017-01-01

    altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18:1), LPC(18:2), LPC(20:3); phosphatidlycholines (PCs) PC(32:2; PC(34:2), PC(36:4), PC(0-34-3) and sphingomyelin (SM) SM(d18:1/24:0)), all...

  13. An Ultra-Wideband Schottky Diode Based Envelope Detector for 2.5 Gbps signals

    DEFF Research Database (Denmark)

    Cimoli, Bruno; Valdecasa, Guillermo Silva; Granja, Angel Blanco

    2016-01-01

    to 2.5 Gbps at 6-9 GHz carrier frequency. The detector uses microstrip and surface-mount device (SMD) components and it is fabricated on a Rogers 6002 substrate. Experimental results show error free transmissions up to 2.5 Gbps at an input power level of -11 dBm. The highest measured conversion gain...

  14. ON THE INCONSISTENCY BETWEEN COSMIC STELLAR MASS DENSITY AND STAR FORMATION RATE UP TO z ∼ 8

    Energy Technology Data Exchange (ETDEWEB)

    Yu, H.; Wang, F. Y., E-mail: fayinwang@nju.edu.cn [School of Astronomy and Space Science, Nanjing University, Nanjing 210093 (China)

    2016-04-01

    In this paper, we test the discrepancy between the stellar mass density (SMD) and instantaneous star formation rate in the redshift range 0 < z < 8 using a large observational data sample. We first compile the measurements of SMDs up to z ∼ 8. Comparing the observed SMDs with the time-integral of instantaneous star formation history (SFH), we find that the observed SMDs are lower than that implied from the SFH at z < 4. We also use the Markov chain Monte Carlo (MCMC) method to derive the best-fitting SFH from the observed SMD data. At 0.5 < z < 6, the observed star formation rate densities are larger than the best-fitting one, especially at z ∼ 2 where they are larger by a factor of about two. However, at lower (z < 0.5) and higher redshifts (z > 6), the derived SFH is consistent with the observations. This is the first time that the discrepancy between the observed SMD and instantaneous star formation rate has been tested up to very high redshift z ≈ 8 using the MCMC method and a varying recycling factor. Several possible reasons for this discrepancy are discussed, such as underestimation of SMD, initial mass function, and evolution of cosmic metallicity.

  15. Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis

    DEFF Research Database (Denmark)

    Johansen, Mette; Bahrt, Henriette; Altman, Roy D

    2016-01-01

    ). METHODS: A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum...

  16. Evaluation of forest thinning materials for TMP production

    Science.gov (United States)

    John H. Klungness; Roland Gleisner; Doreen Mann; Karen L. Scallon; J.Y. Zhu; Eric G. Horn; Louis L. Edwards

    2005-01-01

    We used SilviScan analysis and tracheid measurement to evaluate the effect of suppressed growth on the fundamental properties of wood fiber. Suppressed growth reduced cell tracheid length, but the high content of mature wood may translate into longer fibers overall. In pilot-scale refining experiments, blending 25% chips from small-diameter trees (SMD) with 75% mill...

  17. Feasibility and reliability of the modified berg balance scale in persons with severe intellectual and visual disabilities

    NARCIS (Netherlands)

    Waninge, Aly; van Wijck, R.; Steenbergen, B.; van der Schans, Cees

    2011-01-01

    Background: The purpose of this study was to determine the feasibility and reliability of the modified Berg Balance Scale (mBBS) in persons with severe intellectual and visual disabilities (severe multiple disabilities, SMD) assigned Gross Motor Function Classification System (GMFCS) grades I and

  18. Feasibility and reliability of the modified Berg Balance Scale in persons with severe intellectual and visual disabilities

    NARCIS (Netherlands)

    Waninge, A.; van Wijck, R.; Steenbergen, B.; van der Schans, C. P.

    Background The purpose of this study was to determine the feasibility and reliability of the modified Berg Balance Scale (mBBS) in persons with severe intellectual and visual disabilities (severe multiple disabilities, SMD) assigned Gross Motor Function Classification System (GMFCS) grades I and II.

  19. [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.

  20. The Sound Access Parent Outcomes Instrument (SAPOI): Construction of a new instrument for children with severe multiple disabilities who use cochlear implants or hearing aids.

    Science.gov (United States)

    Hayward, Denyse V; Ritter, Kathryn; Mousavi, Amin; Vatanapour, Shabnam

    2016-01-01

    To report on the Phase 2 development of the Sound Access Parent Outcomes Instrument (SAPOI), a new instrument focused on formalizing outcomes that parents of children with severe multiple disabilities (SMD) who use amplification prioritize as important. Phase 2 of this project involved item selection and refinement of the SAPOI based on (a) Phase 1 study participant input, (b) clinical specialist feedback, and (c) test-retest instrument reliability. Phase 1 participant responses were utilized to construct a draft version of the SAPOI. Next, clinical specialists examined the instrument for content validity and utility and instrument reliability was examined through a test-retest process with parents of children with SMD. The draft SAPOI was constructed based on Phase 1 participant input. Clinical specialists supported content validity and utility of the instrument and the inclusion of 19 additional items across four categories, namely Child Affect, Child Interaction, Parent Well-being, and Child's Device Use. The SAPOI was completed twice at one-month intervals by parents of children with SMD to examine instrument reliability across the four categories (Child Affect, Child Interaction, Parent Well-being, and Child's Device Use). Instrument reliability was strong-to-excellent across all four sections. The SAPOI shows promise as a much-needed addition to the assessment battery currently used for children with SMD who use cochlear implants and hearing aids. It provides valuable information regarding outcomes resulting from access to sound in this population that currently used assessments do not identify.

  1. Reliability and microstructure of lead-free solder joints in industrial electronics after accelerated thermal aging

    NARCIS (Netherlands)

    Scaltro, F.; Biglari, M.H.; Kodentsov, A.; Yakovleva, O.; Brom, E.

    2009-01-01

    The reliability of lead-free (LF) solder joints in surface-mounted device components (SMD) has been investigated after thermo-cycle testing. Kirkendall voids have been observed at the interface component/solder together with the formation of fractures. The evolution, the morphology and the elemental

  2. Funding and Strategic Alignment Guidance for Infusing Small Business Innovation Research Technology into NASA Programs Associated with the Science Mission Directorate

    Science.gov (United States)

    Nguyen, Hung D.; Steele, Gynelle C.

    2015-01-01

    This report is intended to help NASA program and project managers incorporate Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) technologies that have gone through Phase II of the SBIR program into NASA Science Mission Directorate (SMD) programs. Other Government and commercial project managers can also find this information useful.

  3. Cognitive behavioural therapy for ADHD in adults

    DEFF Research Database (Denmark)

    Jensen, Christina Mohr; Amdisen, Birgitte Lind; Jørgensen, Karsten Juhl

    2016-01-01

    Systematically review and analyse the efficacy of CBT versus treatment as usual in adults with ADHD. The literature was systematically searched ending the 28 March 2014. Standardised mean differences (SMD) and 95% confidence intervals were calculated. CBT was efficacious in reducing symptoms of A...

  4. Investigations of the Gas-Liquid Multiphase System Involving Macro-Instability in a Baffled Stirred Tank Reactor

    Directory of Open Access Journals (Sweden)

    Shuo Zhang

    2016-01-01

    Full Text Available Bubble Sauter Mean Diameter (SMD in gas-liquid multiphase system is of particular interest and the quantification of gas characteristics is still a challenge today. In this contribution, multiphase Computational Fluid Dynamic (CFD simulations are combined with Population Balance Model (PBM to investigate the bubble SMD in baffled stirred tank reactor (STR. Hereby, special attention is given to the phenomenon known as the fluid macro-instability (MI, which is a large-scale low-frequency fluid velocity variation in baffled STRs, since the fluid MIs have a dominating influence on the bubble breakage and coalescence processes. The simulations, regarding the fluid velocity, are validated with Laser Doppler Anemometry (LDA experiments, in which the instant radial velocity is analyzed through Fast Fourier Transform (FFT spectrum. The frequency peaks of the fluid MIs are found both in the simulation and in the experiment with a high degree of accuracy. After the validation, quantitative predictions of overall bubble SMD with and without MIs are carried out. Due to the accurate prediction of the fluid field, the influence of the fluid MI to bubble SMD is presented. This result provides more adequate information for engineers working in the field of estimating bubble SMDs in baffled STRs.

  5. Effect of Massage Therapy on Labor Pain Reduction in Primiparous Women: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials in Iran.

    Science.gov (United States)

    Ranjbaran, Mehdi; Khorsandi, Maahboobeh; Matourypour, Pegah; Shamsi, Mohsen

    2017-01-01

    Pain is a common experience for women during labor. Therefore, pain relief care for mothers during labor is very important. This meta-analysis was conducted to evaluate the efficacy of massage therapy on labor pain reduction in primiparous women. In this meta-analysis, the databases of Web of Knowledge, PubMed, Scopus, Cochrane, Iranmedex, Scientific Information Database (SID), and Magiran were searched for published articles in English and Persian language up to January 2016. Among the studies, with regard to the inclusion and exclusion criteria, 10 studies were selected. Data were analyzed by using Stata software version 11, and standard mean difference (SMD) of effects of massage therapy was calculated. The heterogeneity among studies was evaluated by the Chi-square based Q-test and I 2 statistics. The results of Chi-square based on Q-test and I 2 statistics showed heterogeneity among studies in the latent phase ( Q = 63.52, P value massage therapy reduces labor pain in the latent phase (SMD = -1.23, 95% CI: -1.73 to -0.74), active phase (SMD = -1.59, 95% CI: -2.06 to -1.12), and transitional phase (SMD = -1.90, 95% CI: -3.09 to -0.71). This study provides valid evidence for the effect of massage therapy in Iran for labor pain relief. Therefore, the use of massage therapy can be recommended in the primiparous women.

  6. Numerical study of chemical reactions in a surface microdischarge tube with mist flow based on experiment

    International Nuclear Information System (INIS)

    Shibata, T; Nishiyama, H

    2014-01-01

    Recently, a water treatment method of spraying solution into a discharge region has been developed and shows high energy efficiency. In this study, a simulation model of a water treatment method using a surface microdischarge (SMD) tube with mist flow is proposed for further understanding the detailed chemical reactions. Our model has three phases (plasma, gas and liquid) and three simulation steps. The carrier gas is humid air including 2% or 3% water vapour. The chemical species diffusion characteristics in the SMD tube and the concentrations in a droplet are clarified in a wide pH interval. The simulation results show that the chemical species generated on the SMD tube inner wall are diffused to the central axis and dissolved into fine droplets. Especially, OH radicals dissolve into droplets a few mm away from the SMD tube wall because of acidification of the droplets. Furthermore, the hydrogen peroxide density, which is the most important indicator of a radical reaction in water, is influenced by the initial solution pH. This pH dependence results from ozone self-decomposition in water. (paper)

  7. Numerical study of chemical reactions in a surface microdischarge tube with mist flow based on experiment

    Science.gov (United States)

    Shibata, T.; Nishiyama, H.

    2014-03-01

    Recently, a water treatment method of spraying solution into a discharge region has been developed and shows high energy efficiency. In this study, a simulation model of a water treatment method using a surface microdischarge (SMD) tube with mist flow is proposed for further understanding the detailed chemical reactions. Our model has three phases (plasma, gas and liquid) and three simulation steps. The carrier gas is humid air including 2% or 3% water vapour. The chemical species diffusion characteristics in the SMD tube and the concentrations in a droplet are clarified in a wide pH interval. The simulation results show that the chemical species generated on the SMD tube inner wall are diffused to the central axis and dissolved into fine droplets. Especially, OH radicals dissolve into droplets a few mm away from the SMD tube wall because of acidification of the droplets. Furthermore, the hydrogen peroxide density, which is the most important indicator of a radical reaction in water, is influenced by the initial solution pH. This pH dependence results from ozone self-decomposition in water.

  8. The efficacy and safety of Urtica dioica in treating Benign Prostatic ...

    African Journals Online (AJOL)

    Administrator

    Conclusion: This meta-analysis indicates that Urtica dioica to be an effective and ... and no significant adverse effects have been reported by patients after taking ... risk for dichotomous outcomes and the standardized mean difference (SMD) for .... of sex hormone-binding globulin to its receptor on prostate cell membranes ...

  9. Sugarcane Elongin C is involved in infection by sugarcane mosaic disease pathogens.

    Science.gov (United States)

    Zhai, Yushan; Deng, Yuqing; Cheng, Guangyuan; Peng, Lei; Zheng, Yanru; Yang, Yongqing; Xu, Jingsheng

    2015-10-23

    Sugarcane (Saccharum sp. hybrid) provides the main source of sugar for humans. Sugarcane mosaic disease (SMD) is a major threat to sugarcane production. Currently, control of SMD is mainly dependent on breeding resistant cultivars through hybridization, which is time-consuming. Understanding the mechanism of viral infection may facilitate novel strategies to breed cultivars resistant to SMD and to control the disease. In this study, a wide interaction was detected between the viral VPg protein and host proteins. Several genes were screened from sugarcane cDNA library that could interact with Sugarcane streak mosaic virus VPg, including SceIF4E1 and ScELC. ScELC was predicted to be a cytoplasmic protein, but subcellular localization analysis showed it was distributed both in cytoplasmic and nuclear, and interactions were also detected between ScELC and VPg of SCMV or SrMV that reveal ScELC was widely used in the SMD pathogen infection process. ScELC and VPgs interacted in the nucleus, and may function to enhance the viral transcription rate. ScELC also interacted with SceIF4E2 both in the cytoplasm and nucleus, but not with SceIF4E1 and SceIF4E3. These results suggest that ScELC may be essential for the function of SceIF4E2, an isomer of eIF4E. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Peep Vain - koolitaja või vaid õhumüüja? / Siim Saidla

    Index Scriptorium Estoniae

    Saidla, Siim, 1981-

    2002-01-01

    Koolitusfirma Vain SMD juhatuse esimehest ja omanikust Peep Vainust räägivad tema koolitustel osalenud. Lisad: Peep Vainu CV; "Kui täna oleks 6. septembri hommik, siis teeksin teisiti" - katkendid Peep Vainu intervjuust iseendaga. Kommenteerivad Mare Pork ja Aune Past

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 101 - 150 of 641 ... SS Tomar, MD Akheel, SMD Javeed. Vol 4, No 1 ... Vol 4, No 5 (2014), Central Line Associated Blood Stream Infection Rate after Intervention and Comparing Outcome with National Healthcare Safety Network and International Nosocomial Infection Control Consortium Data, Abstract PDF. SZ Bukhari ...

  12. Synchronized droplet size measurements for Coal-Water-Slurry (CWS) diesel sprays of an electronically-controlled fuel injection system

    Science.gov (United States)

    Kihm, K. D.; Terracina, D. P.; Payne, S. E.; Caton, J. A.

    Experiments were completed to study intermittent coal-water slurry (CWS) fuel sprays injected from an electronically-controlled accumulator injector system. A laser diffraction particle analyzing (LDPA) technique was used to measure the spray diameters (Sauter mean diameter, SMD) assuming the Rosin-Rammler two parameter model. In order to ensure an accurate synchronization of the measurement with the intermittent sprays, a new synchronization technique was developed using the light extinction signal as a triggering source for the data taking initiation. This technique allowed measurement of SMD's near the spray tip where the light extinction was low and the data were free from the multiscattering bias. Coal-water slurry fuel with 50% coal loading in mass containing 5 (mu)m mass median diameter coal particulates was considered. Injection pressures ranging from 28 to 110 MPa, two different nozzle orifice diameters, 0.2 ad 0.4 mm, and four axial measurement locations from 60 to 120 mm from the nozzle orifice were studied. Measurements were made for pressurized (2.0 MPa in gauge) and for ambient chamber conditions. The spray SMD showed an increase with the distance of the axial measurement location and with the ambient gas density, and showed a decrease with increasing injection pressure. A correlation of the Sauter mean diameter with the injection conditions was determined. The results were also compared with previous SMD correlations that were available only for diesel fuel sprays.

  13. Static Memory Deduplication for Performance Optimization in Cloud Computing.

    Science.gov (United States)

    Jia, Gangyong; Han, Guangjie; Wang, Hao; Yang, Xuan

    2017-04-27

    In a cloud computing environment, the number of virtual machines (VMs) on a single physical server and the number of applications running on each VM are continuously growing. This has led to an enormous increase in the demand of memory capacity and subsequent increase in the energy consumption in the cloud. Lack of enough memory has become a major bottleneck for scalability and performance of virtualization interfaces in cloud computing. To address this problem, memory deduplication techniques which reduce memory demand through page sharing are being adopted. However, such techniques suffer from overheads in terms of number of online comparisons required for the memory deduplication. In this paper, we propose a static memory deduplication (SMD) technique which can reduce memory capacity requirement and provide performance optimization in cloud computing. The main innovation of SMD is that the process of page detection is performed offline, thus potentially reducing the performance cost, especially in terms of response time. In SMD, page comparisons are restricted to the code segment, which has the highest shared content. Our experimental results show that SMD efficiently reduces memory capacity requirement and improves performance. We demonstrate that, compared to other approaches, the cost in terms of the response time is negligible.

  14. Physical activity for women with breast cancer after adjuvant therapy.

    Science.gov (United States)

    Lahart, Ian M; Metsios, George S; Nevill, Alan M; Carmichael, Amtul R

    2018-01-29

    exercise and resistance training, and seven used resistance training only. Thirty studies described the comparison group as usual or standard care, no intervention, or control. One-fifth of studies reported at least 20% intervention attrition and the average physical activity adherence was approximately 77%.No data were available on effects of physical activity on breast cancer-related and all-cause mortality, or on breast cancer recurrence. Analysis of immediately postintervention follow-up values and change from baseline to end of intervention scores revealed that physical activity interventions resulted in significant small-to-moderate improvements in HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies, 1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively; low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26 studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15 studies, 1579 women, respectively; low-quality evidence), perceived physical function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI 0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence), anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95% CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women, moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women, respectively; very low-quality evidence).Investigators reported few minor adverse events.Small improvements in physical activity interventions were sustained for three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to -0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and self-reported physical activity (SMD 0.44, 95% CI 0

  15. Effect of control and design parameters of injector nozzle on diesel efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Prokopov, N.V.; Burdykin, V.D.

    1981-01-01

    The effect of the rod mass and spring rigidity on the efficiency of the SMD-14N diesel engine is investigated. It is found that by reducing the mass of the movable parts and selection of the rigidity of the spring it is possible to reduce the specific consumption of fuel by 2-5%.

  16. Transmission policy in the United States

    International Nuclear Information System (INIS)

    Joskow, P.L.

    2005-01-01

    This paper provides an overview of the development of electric power transmission access, pricing and investment policies in the US over the last 15 years and evaluates the current state of those policies. Pre-liberalization transmission access and pricing policies are reviewed first since more recent policies have evolved from them. FERC's efforts to ensure that transmission owning utilities provide non-discriminatory access and pricing to wholesale transmission customers, culminating in Order 888 and 889 are discussed. These rules did not respond to problems created by a highly balkanized transmission system and only partially responded to problems caused by common ownership and operation of transmission networks with generating and marketing businesses in the same regions. These problems motivated FERC to seek to create Regional Transmission Organizations (RTO) meeting a long list of criteria related to governance, network operations, transmission pricing and investment as reflected in Order 2000. The slow pace of 'voluntary' reform following Order 2000 led FERC to issue a proposed Standard Market Design Rule (SMD) which provided more detailed prescriptions for wholesale market design, network operations, regional planning, resource adequacy, and transmission investment. The SMD rule confronted enormous resistance from groups of utilities and states that had not embraced an electricity sector liberalization agenda. However, many of the provisions of the SMD are being implemented by the RTOs and ISOs in the Northeast and Midwest. PJM's market rules and transmission pricing, planning and investment policies are reviewed as an articulation of FERC's RTO and SMD visions. (author)

  17. Comparing auditory filter bandwidths, spectral ripple modulation detection, spectral ripple discrimination, and speech recognition: Normal and impaired hearing.

    Science.gov (United States)

    Davies-Venn, Evelyn; Nelson, Peggy; Souza, Pamela

    2015-07-01

    Some listeners with hearing loss show poor speech recognition scores in spite of using amplification that optimizes audibility. Beyond audibility, studies have suggested that suprathreshold abilities such as spectral and temporal processing may explain differences in amplified speech recognition scores. A variety of different methods has been used to measure spectral processing. However, the relationship between spectral processing and speech recognition is still inconclusive. This study evaluated the relationship between spectral processing and speech recognition in listeners with normal hearing and with hearing loss. Narrowband spectral resolution was assessed using auditory filter bandwidths estimated from simultaneous notched-noise masking. Broadband spectral processing was measured using the spectral ripple discrimination (SRD) task and the spectral ripple depth detection (SMD) task. Three different measures were used to assess unamplified and amplified speech recognition in quiet and noise. Stepwise multiple linear regression revealed that SMD at 2.0 cycles per octave (cpo) significantly predicted speech scores for amplified and unamplified speech in quiet and noise. Commonality analyses revealed that SMD at 2.0 cpo combined with SRD and equivalent rectangular bandwidth measures to explain most of the variance captured by the regression model. Results suggest that SMD and SRD may be promising clinical tools for diagnostic evaluation and predicting amplification outcomes.

  18. Comparing auditory filter bandwidths, spectral ripple modulation detection, spectral ripple discrimination, and speech recognition: Normal and impaired hearinga)

    Science.gov (United States)

    Davies-Venn, Evelyn; Nelson, Peggy; Souza, Pamela

    2015-01-01

    Some listeners with hearing loss show poor speech recognition scores in spite of using amplification that optimizes audibility. Beyond audibility, studies have suggested that suprathreshold abilities such as spectral and temporal processing may explain differences in amplified speech recognition scores. A variety of different methods has been used to measure spectral processing. However, the relationship between spectral processing and speech recognition is still inconclusive. This study evaluated the relationship between spectral processing and speech recognition in listeners with normal hearing and with hearing loss. Narrowband spectral resolution was assessed using auditory filter bandwidths estimated from simultaneous notched-noise masking. Broadband spectral processing was measured using the spectral ripple discrimination (SRD) task and the spectral ripple depth detection (SMD) task. Three different measures were used to assess unamplified and amplified speech recognition in quiet and noise. Stepwise multiple linear regression revealed that SMD at 2.0 cycles per octave (cpo) significantly predicted speech scores for amplified and unamplified speech in quiet and noise. Commonality analyses revealed that SMD at 2.0 cpo combined with SRD and equivalent rectangular bandwidth measures to explain most of the variance captured by the regression model. Results suggest that SMD and SRD may be promising clinical tools for diagnostic evaluation and predicting amplification outcomes. PMID:26233047

  19. Effect of antithrombin, protein C and protein S on portal vein thrombosis in liver cirrhosis: a meta-analysis.

    Science.gov (United States)

    Qi, Xingshun; Chen, Hui; Han, Guohong

    2013-07-01

    The effects of antithrombin (AT), protein C (PC) and protein S (PS) on the pathogenesis of portal vein thrombosis (PVT) in liver cirrhosis remain controversial in different studies. In this study, a systematic review and meta-analysis to examine this issue were performed. PubMed database was employed to identify all studies in which AT, PC and PS concentrations were measured in both cirrhotic patients with and without PVT. A standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to evaluate the effect of AT, PC and PS on PVT. Data were pooled using both fixed-effect and random-effect models. Only the pooled data using random-effect model were considered appropriate, when significant heterogeneity was observed. Nine studies involving 160 cirrhotic patients with PVT and 428 cirrhotic patients without PVT were eligible. AT and PC concentrations were similar between PVT and non-PVT groups (AT: SMD = -0.21, 95% CI = -0.56 to 0.14, P = 0.24; PC: SMD = -0.23, 95% CI = -0.55 to 0.09, P = 0.16). But PS concentration was significantly lower in the PVT group than in the non-PVT group (SMD = -0.29, 95% CI = -0.49 to -0.08, P = 0.006). Subgroup analyses were further conducted in 4 studies in which baseline liver function was similar between cirrhotic patients with and without PVT, showing similar AT, PC and PS concentrations between the 2 groups (AT: SMD = -0.10, 95% CI = -0.36 to 0.16, P = 0.57; PC: SMD = -0.18, 95% CI = -0.62 to 0.25, P = 0.41; PS: SMD = -0.10, 95% CI = -0.59 to 0.39, P = 0.69). AT, PC and PS concentrations might not be associated with the pathogenesis of PVT in liver cirrhosis, especially when the impact of liver function was excluded.

  20. Systematic review and meta-analysis of the efficacy and safety of Biqi capsule in rheumatoid arthritis patients.

    Science.gov (United States)

    Chen, Xiu-Min; Wu, Jia-Qi; Huang, Qing-Chun; Zhang, Jian-Yong; Pen, Jian-Hong; Huang, Zhi-Sheng; Chu, Yong-Liang; He, Xiao-Hong; Wang, Mao-Jie; Huang, Run-Yue

    2018-06-01

    Biqi capsule is a Traditional Chinese Medicine preparation for treating rheumatoid arthritis (RA), and clinical studies have indicatedthat its effect may be more beneficial than that of Western medicine. The present study aimed to estimate the efficacy and safety of Biqi capsule alone or combined with methotrexate (MTX) compared with MTX alone for treating RA by performing a meta-analysis of randomized controlled trials and controlled clinical trials. A systematic literature search of studies published until March 2017 was performed. References from relevant studies were screened to obtain additional articles. The results were independently evaluated for relevance, and full-text studies were assessed for eligibility. The risk of bias was assessed using the Cochrane collaboration tool for assessing risk of bias. Out of 558 citations that were initially retrieved, a total of 5 studies comprising 522 patients met the inclusion criteria. The risk of bias of these trials was generally unclear or high. Meta-analysis indicated that Biqi capsule had better effects on C-reactive protein [standardized mean difference (SMD), -7.05; 95% CI -(10.77-3.33)] and tender joint count [SMD, -3.02; 95% CI, -(3.81-2.22)] and fewer adverse effects (AEs) than MTX [relative risk (RR), 0.19; 95% CI, 0.08-0.43]. Biqi capsule plus MTX was superior to MTX in terms of the total effect (RR, 1.17; 95% CI, 1.06-1.28), rheumatoid factor [SMD, -12.54; 95% CI, -(16.87-8.20)], swollen joint count [SMD, -1.50; 95% CI, -(1.99-1.01)], score of joint swelling [SMD -2.07; 95% CI, -(2.76-1.38)], tender joint count [SMD, -2.16; 95% CI, -(2.86-1.47)] and score of joint tenderness [SMD, -4.69; 95% CI, -(5.92-3.47)]. There was no difference in AEs between Biqi capsule plus MTX and MTX (RR, 0.71; 95% CI, 0.34-1.50). In conclusion, the present study indicated that compared with MTX, Biqi capsule plus MTX appeared to have more benefits but that Biqi capsule alone was not better for RA patients than MTX. In the

  1. Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

    Science.gov (United States)

    Ezeamama, Amara E; Bustinduy, Amaya L; Nkwata, Allan K; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J; King, Charles H

    2018-01-01

    By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in

  2. Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Amara E Ezeamama

    2018-01-01

    Full Text Available By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC is associated with educational loss and cognitive deficits.This review was prospectively registered in the PROSPERO database (CRD42016040052. Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD and 95% confidence intervals (CI were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12, scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20, learning (SMD = -0.39, 95%CI: -0.70, -0.09 and memory (SMD = -0.28, 95%CI: -0.52, -0.04 tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30 and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06. Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits

  3. Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis

    Science.gov (United States)

    Wang, Kai; Ju, Qing; Cao, Jing; Tang, Wenze; Zhang, Jian

    2017-01-01

    Abstract Background and objective: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis in general; however, it is heterogeneous to detect relative biomarkers for predicting the disease progression. Serum biomarkers can be conveniently collected to detect and help to differentially diagnose IPF and predict IPF prognosis. This meta-analysis aimed to evaluate the use of serum surfactant proteins A and D (SP-A and SP-D) for differential diagnosis and prognosis of IPF. Methods: Relevant articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases and reviewed by 2 independent readers. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the difference in serum levels of SP-A/D among patients with IPF, when compared to patients with non-IPF interstitial lung disease (ILD), pulmonary infection, and healthy control. Hazard ratio (HR) and 95% CI were used to compare the relative risk of mortality. Results: Twenty-one articles (totalling 1289 IPF patients) were included in final meta-analysis. Serum SP-A levels were significantly higher in patients with IPF than in patients with non-IPF ILD (SMD: 1.108 [0.584, 1.632], P infection (SMD: 1.320 [0.999, 1.640], P SMD: 2.802 [1.901, 3.702], P SMD: 0.459 [−0.000, 0.919], P = .050). Serum SP-D levels were significantly higher in patients with IPF than in patients with pulmonary infection (SMD: 1.308 [0.813, 1.803], P SMD: 2.235 [1.739, 2.731], P < .001). Risk of death in patients with IPF and elevated serum SP-A was increased 39% compared to patients with low SP-A groups. Elevated SP-D increased risk by 111% when compared to low SP-D. In acute exacerbation of IPF, serum SP-A/D were higher than those in stable stage. The comparisons and prognosis might be different in Asian and Caucasian patients. Conclusions: Serum SP-A/D detection might be useful for differential diagnosis and prediction of survival in patients with IPF. PMID:28591049

  4. Comparison of outcomes from smoking and nonsmoking donors: thirteen-year experience.

    Science.gov (United States)

    Berman, Marius; Goldsmith, Kim; Jenkins, David; Sudarshan, Catherine; Catarino, Pedro; Sukumaran, Nair; Dunning, John; Sharples, Linda D; Tsui, Steven; Parmar, Jasvir

    2010-12-01

    Lung transplantation remains the best treatment option for a variety of end-stage lung diseases. Pressure on the limited donor pool has led to the use of extended criteria donors. One aspect of this has been the liberalization of the use of smoking donors (SmD). This study is a retrospective review of lung transplants performed between April 1995 and August 2008 at a single institute. We examined the impact of donor smoking on short-term and long-term survival in relationship to recipient and donor demographics such as ischemic time, cytomegalovirus status, rates of rejection and infection, ventilation, and intensive care stay. Endpoints were survival, infection, and rejection. During this 13-year period, 454 lung transplants were performed. Smoking history was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one patients died within 3 months of transplant leaving 353 alive at 3 months posttransplant. Fatalities within the first 3 months were significantly higher in the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No significant difference in rejection and infection rates between recipients of lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51 and 0.09) was found. Although recipients of lungs from SmD had higher odds of ventilation for more than 10 hours, the odds were only increased by 20%, which was not statistically significant. Recipients from SmD had significantly longer stays in the intensive care (odds ratio 1.9, p = 0.002). There was little evidence for an effect of SmD on the development of bronchiolitis obliterans. In this large cohort of patients, donor smoking history has an effect on early survival but no effect on long-term survival. The cause of this early mortality is independent of infection and rejection. However, these data suggest that overall outcomes from the use of donor lungs from smokers are acceptable, particularly in the current era with limited donor organs

  5. Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Kai; Ju, Qing; Cao, Jing; Tang, Wenze; Zhang, Jian

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) has a poor prognosis in general; however, it is heterogeneous to detect relative biomarkers for predicting the disease progression. Serum biomarkers can be conveniently collected to detect and help to differentially diagnose IPF and predict IPF prognosis. This meta-analysis aimed to evaluate the use of serum surfactant proteins A and D (SP-A and SP-D) for differential diagnosis and prognosis of IPF. Relevant articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases and reviewed by 2 independent readers. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the difference in serum levels of SP-A/D among patients with IPF, when compared to patients with non-IPF interstitial lung disease (ILD), pulmonary infection, and healthy control. Hazard ratio (HR) and 95% CI were used to compare the relative risk of mortality. Twenty-one articles (totalling 1289 IPF patients) were included in final meta-analysis. Serum SP-A levels were significantly higher in patients with IPF than in patients with non-IPF ILD (SMD: 1.108 [0.584, 1.632], P infection (SMD: 1.320 [0.999, 1.640], P SMD: 2.802 [1.901, 3.702], P SMD: 0.459 [-0.000, 0.919], P = .050). Serum SP-D levels were significantly higher in patients with IPF than in patients with pulmonary infection (SMD: 1.308 [0.813, 1.803], P SMD: 2.235 [1.739, 2.731], P < .001). Risk of death in patients with IPF and elevated serum SP-A was increased 39% compared to patients with low SP-A groups. Elevated SP-D increased risk by 111% when compared to low SP-D. In acute exacerbation of IPF, serum SP-A/D were higher than those in stable stage. The comparisons and prognosis might be different in Asian and Caucasian patients. Serum SP-A/D detection might be useful for differential diagnosis and prediction of survival in patients with IPF.

  6. Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis

    Science.gov (United States)

    Bustinduy, Amaya L.; Nkwata, Allan K.; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J.; King, Charles H.

    2018-01-01

    Background By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The

  7. Relationships between craniocervical posture and pain-related disability in patients with cervico-craniofacial pain

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    López-de-Uralde-Villanueva I

    2015-07-01

    Full Text Available Ibai López-de-Uralde-Villanueva,1–4 Hector Beltran-Alacreu,1–3 Alba Paris-Alemany,1–4 Santiago Angulo-Díaz-Parreño,2,3,5 Roy La Touche1–4 1Department of Physiotherapy, Faculty of Health Science, 2Research Group on Movement and Behavioral Science and Study of Pain, The Center for Advanced Studies University La Salle, Universidad Autónoma de Madrid, Aravaca, Madrid, Spain; 3Institute of Neuroscience and Craniofacial Pain (INDCRAN, Madrid, Spain; 4Hospital La Paz Institute for Health Research, IdiPAZ, Madrid, Spain; 5Faculty of Medicine, Universidad San Pablo CEU, Madrid, Spain Objectives: This cross-sectional correlation study explored the relationships between craniocervical posture and pain-related disability in patients with chronic cervico-craniofacial pain (CCFP. Moreover, we investigated the test–retest intrarater reliability of two craniocervical posture measurements: head posture (HP and the sternomental distance (SMD. Methods: Fifty-three asymptomatic subjects and 60 CCFP patients were recruited. One rater measured HP and the SMD using a cervical range of motion device and a digital caliper, respectively. The Spanish versions of the neck disability index and the craniofacial pain and disability inventory were used to assess pain-related disability (neck disability and craniofacial disability, respectively. Results: We found no statistically significant correlations between craniocervical posture and pain-related disability variables (HP and neck disability [r=0.105; P>0.05]; HP and craniofacial disability [r=0.132; P>0.05]; SMD and neck disability [r=0.126; P>0.05]; SMD and craniofacial disability [r=0.195; P>0.05]. A moderate positive correlation was observed between HP and SMD for both groups (asymptomatic subjects, r=0.447; CCFP patients, r=0.52. Neck disability was strongly positively correlated with craniofacial disability (r=0.79; P>0.001. The test–retest intrarater reliability of the HP measurement was high for

  8. Changes in urinary Cu, Zn, and Se levels in cancer patients after treatment with Sha Shen Mai Men Dong Tang

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    Tung-Yuan Lai

    2016-04-01

    Full Text Available Sha Shen Mai Men Dong Tang (SMD-2; 沙參麥冬湯 shā shēn mài dōng tāng is a Chinese medicinal herb (CMH; 中草藥 zhōng cǎo yào used to treat symptoms associated with cancer therapy. The objective of this study was to assess the effect of SMD-2 on the levels of urinary copper (Cu, zinc (Zn, and selenium (Se in lung cancer patients and head and neck cancer patients receiving chemoradiotherapy. Forty-two head and neck cancer patients and 10 lung cancer patients participated in our clinical trial. Each patient received chemoradiotherapy for 4 weeks. In addition, each patient was treated with SMD-2 for 8 weeks, including 2 weeks prior to and after the chemoradiotherapy treatment. Comparison of urinary Cu, Zn, and Se levels and the ratios of Zn to Cu and Se to Cu at three time points in the two types of cancer were assessed using the generalized estimating equations (GEEs. After the patients received chemoradiotherapy for 4 weeks, SMD-2 treatment was found to be associated with a significant decrease in urinary Cu levels, whereas urinary Zn and Se levels increased significantly. In addition, the ratios of Zn to Cu and Se to Cu in the urine samples of these patients also increased significantly. Both the urinary Zn levels and the ratio of Zn to Cu in head and neck cancer patients were significantly higher than in lung cancer patients. Urinary Zn and Se levels and the ratios of Zn to Cu and Se to Cu, but not urinary Cu levels, increased significantly during and after treatment when assessed using the GEE model. The SMD-2 treatments significantly increased Zn and Se levels in the urine of head and neck cancer patients. Increased Zn and Se levels in urine strengthened immune system.

  9. The Effectiveness of Green Tea or Green Tea Extract on Insulin Resistance and Glycemic Control in Type 2 Diabetes Mellitus: A Meta-Analysis

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    Jinyue Yu

    2017-08-01

    Full Text Available Green tea or green tea extract (GT/GTE has been demonstrated to reduce insulin resistance and improve glycemic control. However, evidence for this health beneficial effect is inconsistent. This systematic review evaluated the effect of GT/GTE on insulin resistance and glycemic control in people with pre-diabetes/type 2 diabetes mellitus (T2DM. Ovid MEDLINE, Embase, AMED, Web of Science, and the Cochrane Library were searched up to April 2017 for randomised controlled trials of participants with pre-diabetes or T2DM, where the intervention was GT/GTE. Meta-analysis was performed to assess the standardised mean difference (SMD in biomarkers of insulin resistance and glycemic control between GT/GTE and placebo groups. Six studies (n=382 were pooled into random-effects meta-analysis. Overall, no differences were found between GT/GTE and the placebo for glycosylated hemoglobin (HbA1c: SMD, −0.32; 95% confidence interval [CI], −0.86 to 0.23, homeostatic model assessment for insulin resistance (HOMA-IR: SMD, 0.10; 95% CI, −0.17 to 0.38, fasting insulin (SMD, −0.25; 95% CI, −0.64 to 0.15, and fasting glucose (SMD, −0.10; 95% CI, −0.50 to 0.30. No evidence support the consumption of GT/GTE could reduce the levels of HbA1c, HOMA-IR, fasting insulin, or fasting glucose in people with pre-diabetes/T2DM. However, the studies included were small and of varying quality.

  10. EEG Neurofeedback treatments in children with ADHD: An updated meta-analysis of Randomized Controlled Trials

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    Jean-Arthur eMicoulaud Franchi

    2014-11-01

    Full Text Available Objective We undertook a meta-analysis of published Randomized Controlled Trials (RCT with semi-active control and sham-NF groups to determine whether EEG-NF significantly improves the overall symptoms, inattention and hyperactivity/impulsivity dimensions for probably unblinded assessment (parent assessment and probably blinded assessment (teacher assessment in children with Attention Deficit Hyperactivity Disorder (ADHD.Data Sources A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis.Data Extraction Effect sizes for ADHD symptoms were expressed as standardized mean differences (SMD with 95% confidence intervals.ResultsFive identified studies met eligibility criteria, 263 patients with ADHD were included, 146 patients were trained with EEG-NF. On parent assessment (probably unblinded assessment, the overall ADHD score (SMD=-0.49 [-0.74, -0.24], the inattention score (SMD=-0.46 [-0.76, -0.15] and the hyperactivity/impulsivity score (SMD=-0.34 [-0.59, -0.09] were significantly improved in patients receiving EEG-NF compared to controls. On teacher assessment (probably blinded assessment, only the inattention score was significantly improved in patients receiving EEG-NF compared to controls (SMD=-0.30 [-0.58, -0.03]. ConclusionsThis meta-analysis of EEG-NF in children with ADHD highlights improvement in the inattention dimension of ADHD symptoms. Future investigations should pay greater attention to adequately blinded studies and EEG-NF protocols that carefully control the implementation and embedding of training.

  11. Assessment of response to endocrine therapy using FDG PET/CT in metastatic breast cancer: a pilot study

    International Nuclear Information System (INIS)

    Mortazavi-Jehanno, Nina; Giraudet, Anne-Laure; Champion, Laurence; Edeline, Veronique; Madar, Olivier; Pecking, Alain Paul; Lerebours, Florence; Stanc, Elise Le; Bellet, Dominique; Alberini, Jean-Louis

    2012-01-01

    The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by 18 F-FDG PET/CT. The study group comprised 22 patients with breast cancer (age 58 ± 11 years, mean ± SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 ± 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV max between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS. (orig.)

  12. Assessment of response to endocrine therapy using FDG PET/CT in metastatic breast cancer: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Mortazavi-Jehanno, Nina; Giraudet, Anne-Laure; Champion, Laurence; Edeline, Veronique; Madar, Olivier; Pecking, Alain Paul [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Lerebours, Florence [Institut Curie, Hopital Rene Huguenin, Service d' Oncologie Medicale, Saint-Cloud (France); Stanc, Elise Le [Hopital Foch, Service de Medecine Nucleaire, Suresnes (France); Bellet, Dominique [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Universite Paris Descartes, Pharmacologie Chimique et Genetique and Imagerie, Inserm U1022 CNRS UMR 8151, Faculte des sciences pharmaceutiques et biologiques, Paris (France); Alberini, Jean-Louis [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Universite Versailles Saint-Quentin, Faculte de Medecine, Versailles (France)

    2012-03-15

    The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by {sup 18}F-FDG PET/CT. The study group comprised 22 patients with breast cancer (age 58 {+-} 11 years, mean {+-} SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 {+-} 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV{sub max} between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS. (orig.)

  13. Computer-Based Cognitive Programs for Improvement of Memory, Processing Speed and Executive Function during Age-Related Cognitive Decline: A Meta-Analysis.

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    Yan-kun Shao

    Full Text Available Several studies have assessed the effects of computer-based cognitive programs (CCP in the management of age-related cognitive decline, but the role of CCP remains controversial. Therefore, this systematic review evaluated the evidence on the efficacy of CCP for age-related cognitive decline in healthy older adults.Six electronic databases (through October 2014 were searched. The risk of bias was assessed using the Cochrane Collaboration tool. The standardized mean difference (SMD and 95% confidence intervals (CI of a random-effects model were calculated. The heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index.Twelve studies were included in the current review and were considered as moderate to high methodological quality. The aggregated results indicate that CCP improves memory performance (SMD, 0.31; 95% CI 0.16 to 0.45; p < 0.0001 and processing speed (SMD, 0.50; 95% CI 0.14 to 0.87; p = 0.007 but not executive function (SMD, -0.12; 95% CI -0.33 to 0.09; p = 0.27. Furthermore, there were long-term gains in memory performance (SMD, 0.59; 95% CI 0.13 to 1.05; p = 0.01.CCP may be a valid complementary and alternative therapy for age-related cognitive decline, especially for memory performance and processing speed. However, more studies with longer follow-ups are warranted to confirm the current findings.

  14. Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

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    Li Wang

    Full Text Available Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT. The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT.PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN use, and length of hospital stay.Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99 and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25. In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively. However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively.Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

  15. Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

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    Yan-hui Li

    Full Text Available BACKGROUND: Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM, the role of massage therapy in the management of FM remained controversial. OBJECTIVE: The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. METHODS: Electronic databases (up to June 2013 were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD and 95% confidence intervals (CI were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2 statistic. RESULTS: Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03, anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01, and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005 in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52. CONCLUSION: Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

  16. Anxiety, depression, and health-related quality of life in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis.

    Science.gov (United States)

    Akioyamen, Leo E; Genest, Jacques; Shan, Shubham D; Inibhunu, Happy; Chu, Anna; Tu, Jack V

    2018-06-01

    Heterozygous familial hypercholesterolemia (FH) is a common genetic disease predisposing affected individuals to a high risk of cardiovascular disease. Yet, considerable uncertainty exists regarding its impact on psychosocial wellbeing. We performed a systematic review and meta-analysis of the association between FH and symptoms of anxiety and depression, and health-related quality of life (HRQL). We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO, and PubMed for peer-reviewed literature published in English between January 1, 1990 and January 1, 2018. Quantitative and qualitative studies were eligible if they included patients with confirmed FH and evaluated its association with symptoms of anxiety or depression, or HRQL. We performed a narrative synthesis of studies, including thematic analysis of qualitative studies, and where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals. We found 10 eligible studies measuring HRQL, depression and anxiety. Random-effects meta-analysis of 4 (n = 4293) and 5 studies (n = 5098), respectively, showed that patients with FH had slightly lower symptoms of anxiety (SMD: -0.29 [95% CI: -0.53, -0.04]) and mental HRQL (SMD: -0.10 [95% -0.20, -0.00]) relative to general population controls. No significant differences existed in depressive symptoms (SMD: 0.04 [95% CI: -0.12, 0.19]) or physical HRQL scores (SMD: 0.02 [95% CI: -0.09, 0.12]). Our systematic review suggests that patients with FH may report small but measurable differences in anxiety symptoms and mental HRQL. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Li; Gu, Zhenyang; Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji

    2015-01-01

    Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

  18. Massage Therapy for Neck and Shoulder Pain: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ling Jun Kong

    2013-01-01

    Full Text Available Objective. To evaluate the effectiveness of massage therapy (MT for neck and shoulder pain. Methods. Seven English and Chinese databases were searched until December 2011 for randomized controlled trials (RCTs of MT for neck and shoulder pain. The methodological quality of RCTs was assessed based on PEDro scale. The meta-analyses of MT for neck and shoulder pain were performed. Results. Twelve high-quality studies were included. In immediate effects, the meta-analyses showed significant effects of MT for neck pain (standardised mean difference, SMD, 1.79; 95% confidence intervals, CI, 1.01 to 2.57; P<0.00001 and shoulder pain (SMD, 1.50; 95% CI, 0.55 to 2.45; P=0.002 versus inactive therapies. And MT showed short-term effects for shoulder pain (SMD, 1.51; 95% CI, 0.53 to 2.49; P=0.003. But MT did not show better effects for neck pain (SMD, 0.13; 95% CI, −0.38 to 0.63; P=0.63 or shoulder pain (SMD, 0.88; 95% CI, −0.74 to 2.51; P=0.29 than active therapies. In addition, functional status of the shoulder was not significantly affected by MT. Conclusion. MT may provide immediate effects for neck and shoulder pain. However, MT does not show better effects on pain than other active therapies. No evidence suggests that MT is effective in functional status.

  19. Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

    2014-01-01

    Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2) statistic. Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52). Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

  20. Impact of lifestyle interventions on depressive symptoms in individuals at-risk of, or with, type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Cezaretto, A; Ferreira, S R G; Sharma, S; Sadeghirad, B; Kolahdooz, F

    2016-08-01

    Depression affects one in four individuals with type 2 diabetes mellitus (T2DM). The impact of T2DM lifestyle interventions on depression is unclear. The aim of this analysis was to examine the influence of lifestyle interventions on depressive symptoms scores in individuals at-risk of or with T2DM. Major bibliographic databases were searched for studies published in English from 1990 to 2015. Meta-analysis was conducted by random-effects model. Nineteen studies were included in the meta-analyses. A significant reduction in depression scores was shown for lifestyle interventions in the pooled analysis (Standardized Mean Difference (SMD): -0.165; 95%CI: -0.265, -0.064; I(2):67.9%) and when limited to individuals with T2DM (SMD: -0.202; 95%CI: -0.288, -0.079; I(2):72.5%). In subgroup analyses the most effective intervention methods were face-to-face individual consultations (SMD: -0.241; 95%CI: -0.403, -0.078, I(2): 50.8%) with a duration of ≤6 months (SMD: -0.203; 95%CI: -0.381, -0.026, I(2):59.9%). Interventions were most effective when delivered four times a month (SMD: -0.247; 95%CI: -0.441, -0.053, I(2):76.3%). Lifestyle interventions were effective in improving depression among people with T2DM. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  1. Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Li, Sheyu; Wei, Jia; Zhang, Chenghui; Li, Xiaodan; Meng, Wentong; Mo, Xianming; Zhang, Qianying; Liu, Qilin; Ren, Kaiyun; Du, Rong; Tian, Haoming; Li, Jianwei

    2016-01-01

    The aim of this study was to assess the association between circulating cell-derived microparticles (MPs) and type 2 diabetes mellitus (T2DM). A literature search was performed systematically in PubMed and Embase to identify available case-control or cross-sectional studies that compared different types of cell-derived MPs in patients with T2DM and non-diabetic controls. Pooled standardized mean differences (SMDs) of each MP type were pooled using meta-analysis. Forty-eight studies involving 2,460 patients with T2DM and 1,880 non-diabetic controls were included for systematic review and 34 of which were included for quantitative study by meta-analysis. In the overall analysis, the levels of circulating total MPs (TMPs), platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs) and endothelium-derived MPs (EMPs) were significantly higher in T2DM patients than those in controls (TMPs: SMD, 0.64; 95%CI, 0.12∼1.15; P=0.02; PMPs: SMD, 1.19; 95%CI, 0.88∼1.50; P <0.00001; MMPs: SMD, 0.92; 95%CI, 0.66∼1.17; P <0.00001; EMPs: SMD, 0.73; 95%CI, 0.50∼0.96; P <0.00001). Meanwhile, no significant difference was shown in leukocyte-derived MPs (LMPs) level between diabetic and non-diabetic groups (SMD, 0.37; 95%CI, -0.15∼0.89; P=0.17). The counts of TMPs, PMPs, MMPs and EMPs elevated in patients with T2DM. And cell-derived MPs may play a role in the pathogenesis of T2DM. © 2016 The Author(s) Published by S. Karger AG, Basel.

  2. Mindfulness-based therapies in the treatment of somatization disorders: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shaheen E Lakhan

    Full Text Available BACKGROUND: Mindfulness-based therapy (MBT has been used effectively to treat a variety of physical and psychological disorders, including depression, anxiety, and chronic pain. Recently, several lines of research have explored the potential for mindfulness-therapy in treating somatization disorders, including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. METHODS: Thirteen studies were identified as fulfilling the present criteria of employing randomized controlled trials to determine the efficacy of any form of MBT in treating somatization disorders. A meta-analysis of the effects of mindfulness-based therapy on pain, symptom severity, quality of life, depression, and anxiety was performed to determine the potential of this form of treatment. FINDINGS: While limited in power, the meta-analysis indicated a small to moderate positive effect of MBT (compared to wait-list or support group controls in reducing pain (SMD = -0.21, 95% CI: -0.37, -0.03; p<0.05, symptom severity (SMD = -0.40, 95% CI: -0.54, -0.26; p<0.001, depression (SMD = -0.23, 95% CI: -0.40, -0.07, p<0.01, and anxiety (SMD = -0.20, 95% CI: -0.42, 0.02, p = 0.07 associated with somatization disorders, and improving quality of life (SMD = 0.39, 95% CI: 0.19, 0.59; p<0.001 in patients with this disorder. Subgroup analyses indicated that the efficacy of MBT was most consistent for irritable bowel syndrome (p<0.001 for pain, symptom severity, and quality of life, and that mindfulness-based stress reduction (MBSR and mindfulness-based cognitive therapy (MCBT were more effective than eclectic/unspecified MBT. CONCLUSIONS: Preliminary evidence suggests that MBT may be effective in treating at least some aspects of somatization disorders. Further research is warranted.

  3. Use of simulation-based education to improve outcomes of central venous catheterization: a systematic review and meta-analysis.

    Science.gov (United States)

    Ma, Irene W Y; Brindle, Mary E; Ronksley, Paul E; Lorenzetti, Diane L; Sauve, Reg S; Ghali, William A

    2011-09-01

    Central venous catheterization (CVC) is increasingly taught by simulation. The authors reviewed the literature on the effects of simulation training in CVC on learner and clinical outcomes. The authors searched computerized databases (1950 to May 2010), reference lists, and considered studies with a control group (without simulation education intervention). Two independent assessors reviewed the retrieved citations. Independent data abstraction was performed on study design, study quality score, learner characteristics, sample size, components of interventional curriculum, outcomes assessed, and method of assessment. Learner outcomes included performance measures on simulators, knowledge, and confidence. Patient outcomes included number of needle passes, arterial puncture, pneumothorax, and catheter-related infections. Twenty studies were identified. Simulation-based education was associated with significant improvements in learner outcomes: performance on simulators (standardized mean difference [SMD] 0.60 [95% CI 0.45 to 0.76]), knowledge (SMD 0.60 [95% CI 0.35 to 0.84]), and confidence (SMD 0.41 [95% CI 0.30 to 0.53] for studies with single-group pretest and posttest design; SMD 0.52 (95% CI 0.23 to 0.81) for studies with nonrandomized, two-group design). Furthermore, simulation-based education was associated with improved patient outcomes, including fewer needle passes (SMD -0.58 [95% CI -0.95 to -0.20]), and pneumothorax (relative risk 0.62 [95% CI 0.40 to 0.97]), for studies with nonrandomized, two-group design. However, simulation-based training was not associated with a significant reduction in risk of either arterial puncture or catheter-related infections. Despite some limitations in the literature reviewed, evidence suggests that simulation-based education for CVC provides benefits in learner and select clinical outcomes.

  4. IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

    Science.gov (United States)

    Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

    2012-05-10

    Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

  5. Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

    Science.gov (United States)

    Rapoport, Basil

    2014-01-01

    Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

  6. Rapid induction of autoantibodies during ARDS and septic shock

    Directory of Open Access Journals (Sweden)

    Meduri G Umberto

    2010-10-01

    Full Text Available Abstract Background Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction. Methods Using Luciferase Immunoprecipitation Systems (LIPS, a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time. Results From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected. Conclusion The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.

  7. Expression of Toll-like receptors and their detection of nuclear self-antigen leading to immune activation in JSLE.

    Science.gov (United States)

    Midgley, Angela; Thorbinson, Colin; Beresford, Michael W

    2012-05-01

    Toll-like receptors (TLRs) essential in the functioning of the immune system have been implicated in the development of autoimmunity. TLR3, 7, 8 and 9 are capable of recognizing nucleic autoantigens typical of SLE. Their expression correlates positively with disease activity in adult-onset SLE. This study aimed to determine the role of TLRs in JSLE and whether apoptotic neutrophils are a source of nuclear autoantigen being detected through TLR3, 7, 8 and 9, leading to an inflammatory response. TLR3, 7, 8 and 9 mRNA and protein expression were measured in peripheral blood mononuclear cells (PBMCs) in JSLE patients compared with JIA and non-inflammatory controls. Activation of the TLRs by JSLE serum-induced apoptotic neutrophils was detected by measuring IFN-α mRNA and protein expression, and confirmed using myeloid differentiation factor 88 (MyD88) and TIR domain-containing adapter-inducing IFN-β (TRIF) inhibitors. JSLE patients have increased TLR3, 8 and 9 mRNA and protein expression compared with controls (P < 0.05). Incubation of PBMCs with apoptotic neutrophils demonstrated a dose-response relationship for IFN-α mRNA expression. Inhibition of TLR signalling by blocking MyD88 and TRIF signalling decreased IFN-α mRNA expression in PBMCs incubated with apoptotic neutrophils (P < 0.05). This study demonstrated significantly increased TLR expression in JSLE compared with controls. Our data indicate that apoptotic neutrophils trigger TLR activation through their presentation of autoantigens. The role of TLRs in this inflammatory response was demonstrated by a dose-response relationship to apoptotic neutrophil concentration and confirmed by a decrease in IFN-α production after inhibition of TLR signalling.

  8. Immuno-chemistry of hydroxyl radical modified GAD-65: A possible role in experimental and human diabetes mellitus.

    Science.gov (United States)

    Moinuddin; Ansari, Nadeem A; Shahab, Uzma; Habeeb, Safia; Ahmad, Saheem

    2015-10-01

    The repertoire of known auto-antigens is limited to a very small proportion of all human proteins, and the reason why only some proteins become auto-antigens is unclear. The 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD-65) is a major auto-antigen in type I diabetes, and in various neurological diseases. Most patients with type I diabetes (70-80%) have auto-antibodies against GAD-65, which often appear years before clinical onset of the autoimmune diabetes. Thus, the aim of the study is to focus on the immunogenicity of GAD65 and its reactive oxygen species (ROS) conformer in STZ-induced diabetic rats and on human diabetic patients. In the present study, GAD-65 was modified by hydroxyl radical following Fenton's reaction. The modifications in the structure of the GAD-65 are supported by UV-vis and fluorescence spectral studies. Immunogenicity of both native and hydroxyl radical modified GAD-65 (ROS-GAD-65) was studied in experimental rabbits and was confirmed by inducing type I diabetes in experimental male albino rats using streptozotocin (45 mg/kg). We found that ROS-GAD-65 was a better immunogen as compared to the native GAD-65. A considerable high binding to ROS-GAD-65 was observed as compared to native GAD-65 in both the serum antibodies from diabetes animal models and as well as in the serum samples of type I diabetes. Hydrogen peroxide under the exposure of UV light produces hydroxyl radical (·OH) which is most potent oxidant, and could cause protein damage (GAD-65) to the extent of generating neo-epitopes on the molecule, thus making it immunogenic. © 2015 International Union of Biochemistry and Molecular Biology.

  9. Elevated expression of the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma

    OpenAIRE

    Barghash, Ahmad; Golob-Schwarzl, Nicole; Helms, Volkhard; Haybaeck, Johannes; Kessler, Sonja M.

    2016-01-01

    Esophageal adenocarcinoma (EAC) represents the sixth leading cause of cancer-related deaths and develops in Barret's esophagus affected tissues. The IGF2 mRNA binding protein IMP2/IGF2BP2/p62 was originally identified as an autoantigen in hepatocellular carcinoma. Aim of this study was to investigate the expression and prognostic role of IMP2 in EAC. Human EAC and Barret's esophagus tissue showed overexpression of IMP2, particularly in tumors of increased size and in metastatic tissues. Molec...

  10. Treatment of renal manifestations of ANCA-associated vasculitis.

    Science.gov (United States)

    Galesic, Kresimir; Ljubanovic, Danica; Horvatic, Ivica

    2013-01-01

    Vasculitis is a clinicopathological entity characterized by inflammation and necrosis of blood vessels. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Two major autoantigens for ANCA are myeloperoxidase (MPO) and proteinase 3 (PR3), which are proteins in the primary granules of neutrophils and in the lysosomes of monocytes. They are expressed in mature neutrophils of patients with ANCA, while absent in healthy subjects. The kidney is the most commonly affected vital organ in ANCA-associated vasculitis, and patient outcomes are largely determined by the severity of renal disease at diagnosis and by its response to treatment.

  11. Structural insight into the function of myelin basic protein as a ligand for integrin αMβ2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano; Gjelstrup, Mikkel Carstensen

    2008-01-01

    protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate......Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic...

  12. Polymeric Gene Delivery for Diabetic Treatment

    Directory of Open Access Journals (Sweden)

    Sung Wan Kim

    2011-08-01

    Full Text Available Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4 were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal.

  13. No Contribution of GAD-65 and IA-2 Autoantibodies around Time of Diagnosis to the Increasing Incidence of Juvenile Type 1 Diabetes

    DEFF Research Database (Denmark)

    Thorsen, Steffen U.; Pipper, Christian B.; Mortensen, Henrik B.

    2016-01-01

    Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D) has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma...... associated antigen-2A (IA-2A) mirrored the 3.4% annual increase in incidence of T1D. Methods. From the Danish Childhood Diabetes Register, we randomly selected 500 patients and 500 siblings for GADA and IA-2A analysis (1997 through 2005). Blood samples were taken within three months after onset. A robust log...

  14. The master two-dimensional gel database of human AMA cell proteins: towards linking protein and genome sequence and mapping information (update 1991)

    DEFF Research Database (Denmark)

    Celis, J E; Leffers, H; Rasmussen, H H

    1991-01-01

    autoantigens" and "cDNAs". For convenience we have included an alphabetical list of all known proteins recorded in this database. In the long run, the main goal of this database is to link protein and DNA sequencing and mapping information (Human Genome Program) and to provide an integrated picture......The master two-dimensional gel database of human AMA cells currently lists 3801 cellular and secreted proteins, of which 371 cellular polypeptides (306 IEF; 65 NEPHGE) were added to the master images during the last 10 months. These include: (i) very basic and acidic proteins that do not focus...

  15. Citrullination: the loss of tolerance and development of autoimmunity in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    G. Ferraccioli

    2011-09-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by synovial inflammation and pannus formation, which can lead to severe destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Moreover the presence of autoantibodies to citrullinated proteins in sera of patients with RA enhances the strength of this hypothesis. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as phosphorylation, glycosylation and citrullination can increase the morphological and the functional diversity of the proteome.

  16. V(D)J recombination process and the Pre-B to immature B-cells transition are altered in Fanca ?/? mice

    OpenAIRE

    Nguyen, Thuy Vy; Pawlikowska, Patrycja; Firlej, Virginie; Rosselli, Filippo; Aoufouchi, Sa?d

    2016-01-01

    B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor and overcome the negative selection induced by reactivity with autoantigens. Two rounds of DNA recombination are required for the production of functional immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the continuation of B-lymphocyte development in the BM. Both rounds depend on the joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases with the DNA non-homologous end-...

  17. Non-MHC Antigenic Targets of the Humoral Immune Response in Transplantation

    OpenAIRE

    Zhang, Qiuheng; Reed, Elaine F.

    2010-01-01

    There is a growing body of data supporting a role for non-HLA antibodies in acute and chronic rejection of solid organ transplants. While many of these non-HLA antigens remain poorly defined, the principle antigenic targets are expressed on cells of the allograft including endothelium and epithelium. These non-HLA antigens are classified as either alloantigens, such as the major histocompatibility complex class I chain-related gene A (MICA) or MICB, or tissue-specific autoantigens such as vim...

  18. Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis

    OpenAIRE

    Muratori, L; Cataleta, M; Muratori, P; Lenzi, M; Bianchi, F

    1998-01-01

    Background—Liver/kidney microsomal antibody type 1 (LKM1) and liver cytosol antibody type 1 (LC1) are the serological markers of type 2 autoimmune hepatitis (AIH). 
Aims—Since LKM1 and LC1 react against two distinct liver specific autoantigens (cytochrome P450IID6 (CYP2D6) and a 58 kDa cytosolic polypeptide respectively), the aim was to see whether LKM1 and LC1 concentrations correlate with liver disease activity. 
Patients—Twenty one patients with type 2 AIH were studied. 
Methods—A...

  19. iStent as a Solo Procedure for Glaucoma Patients: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Malvankar-Mehta, Monali S; Chen, Yufeng Nancy; Iordanous, Yiannis; Wang, Wan Wendy; Costella, John; Hutnik, Cindy M L

    2015-01-01

    Glaucoma is a leading cause of irreversible blindness. It is firmly entrenched in the traditional treatment paradigm to start with pharmacotherapy. However, pharmacotherapy is not benign and has been well documented to have a number of significant challenges. Minimally invasive glaucoma surgery (MIGS) that targets the outflow pathway with minimal to no scleral dissection has resulted in the need to reconsider the glaucoma treatment paradigm. To perform a systematic review and meta-analysis to evaluate and quantify the effect on post-operative intraocular pressure (IOP) and number of topical glaucoma medications, in patients receiving the iStent MIGS device as the solo procedure without concurrent cataract surgery. A systematic review was conducted by searching various databases between January 1, 2000, and June 30, 2014. Studies reporting up to a maximum follow-up period of 24 months were retrieved and screened using the EPPI-Reviewer 4 gateway. Percentage reduction in IOP (IOPR%), and mean reduction in topical glaucoma medications after surgery were computed. Meta-analysis was performed using STATA v. 13.0. The standardized mean difference (SMD) was calculated as the effect size for continuous scale outcomes. Heterogeneity was determined using the I2 statistics, Z-value, and χ2 statistics. Fixed-effect and random-effect models were developed based on heterogeneity. Sub-group analysis was performed based on the number of iStents implanted and the follow-up period. The outcome measures were changes in the IOP and number of glaucoma medications. The search strategy identified 105 records from published literature and 9 records from the grey literature. Five studies with 248 subjects were included for quantitative synthesis. A 22% IOP reduction (IOPR%) from baseline occurred at 18-months after one iStent implant, 30% at 6-months after two iStents implantations, and 40% at 6-months after implantation of three iStents. A mean reduction of 1.2 bottles per patient of

  20. Interventions for Adolescent Mental Health: An Overview of Systematic Reviews.

    Science.gov (United States)

    Das, Jai K; Salam, Rehana A; Lassi, Zohra S; Khan, Marium Naveed; Mahmood, Wajeeha; Patel, Vikram; Bhutta, Zulfiqar A

    2016-10-01

    Many mental health disorders emerge in late childhood and early adolescence and contribute to the burden of these disorders among young people and later in life. We systematically reviewed literature published up to December 2015 to identify systematic reviews on mental health interventions in adolescent population. A total of 38 systematic reviews were included. We classified the included reviews into the following categories for reporting the findings: school-based interventions (n = 12); community-based interventions (n = 6); digital platforms (n = 8); and individual-/family-based interventions (n = 12). Evidence from school-based interventions suggests that targeted group-based interventions and cognitive behavioral therapy are effective in reducing depressive symptoms (standard mean difference [SMD]: -.16; 95% confidence interval [CI]: -.26 to -.05) and anxiety (SMD: -.33; 95% CI: -.59 to -.06). School-based suicide prevention programs suggest that classroom-based didactic and experiential programs increase short-term knowledge of suicide (SMD: 1.51; 95% CI: .57-2.45) and knowledge of suicide prevention (SMD: .72; 95% CI: .36-1.07) with no evidence of an effect on suicide-related attitudes or behaviors. Community-based creative activities have some positive effect on behavioral changes, self-confidence, self-esteem, levels of knowledge, and physical activity. Evidence from digital platforms supports Internet-based prevention and treatment programs for anxiety and depression; however, more extensive and rigorous research is warranted to further establish the conditions. Among individual- and family-based interventions, interventions focusing on eating attitudes and behaviors show no impact on body mass index (SMD: -.10; 95% CI: -.45 to .25); Eating Attitude Test (SMD: .01; 95% CI: -.13 to .15); and bulimia (SMD: -.03; 95% CI: -.16 to .10). Exercise is found to be effective in improving self-esteem (SMD: .49; 95% CI: .16-.81) and reducing

  1. Exercise in prevention and treatment of anxiety and depression among children and young people.

    Science.gov (United States)

    Larun, L; Nordheim, L V; Ekeland, E; Hagen, K B; Heian, F

    2006-07-19

    Depression and anxiety are common psychological disorders for children and adolescents. Psychological (e.g. psychotherapy), psychosocial (e.g. cognitive behavioral therapy) and biological (e.g. SSRIs or tricyclic drugs) treatments are the most common treatments being offered. The large variety of therapeutic interventions give rise to questions of clinical effectiveness and side effects. Physical exercise is inexpensive with few, if any, side effects. To assess the effects of exercise interventions in reducing or preventing anxiety or depression in children and young people up to 20 years of age. We searched the Cochrane Controlled Trials Register (latest issue available), MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC and Sportdiscus up to August 2005. Randomised trials of vigorous exercise interventions for children and young people up to the age of 20, with outcome measures for depression and anxiety. Two authors independently selected trials for inclusion, assessed methodological quality and extracted data. The trials were combined using meta-analysis methods. A narrative synthesis was performed when the reported data did not allow statistical pooling. Sixteen studies with a total of 1191 participants between 11 and 19 years of age were included.Eleven trials compared vigourous exercise versus no intervention in a general population of children. Six studies reporting anxiety scores showed a non-significant trend in favour of the exercise group (standard mean difference (SMD) (random effects model) -0.48, 95% confidence interval (CI) -0.97 to 0.01). Five studies reporting depression scores showed a statistically significant difference in favour of the exercise group (SMD (random effects model) -0.66, 95% CI -1.25 to -0.08). However, all trials were generally of low methodological quality and they were highly heterogeneous with regard to the population, intervention and measurement instruments used. One small trial investigated children in treatment showed no

  2. Yoga for improving health-related quality of life, mental health and cancer-related symptoms in women diagnosed with breast cancer.

    Science.gov (United States)

    Cramer, Holger; Lauche, Romy; Klose, Petra; Lange, Silke; Langhorst, Jost; Dobos, Gustav J

    2017-01-03

    ) with 95% confidence intervals (CIs) and conducted random-effects model meta-analyses. We assessed potential risk of publication bias through visual analysis of funnel plot symmetry and heterogeneity between studies by using the Chi 2 test and the I 2 statistic. We conducted subgroup analyses for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention. We included 24 studies with a total of 2166 participants, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias.Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life (pooled SMD 0.22, 95% CI 0.04 to 0.40; 10 studies, 675 participants), reduced fatigue (pooled SMD -0.48, 95% CI -0.75 to -0.20; 11 studies, 883 participants) and reduced sleep disturbances in the short term (pooled SMD -0.25, 95% CI -0.40 to -0.09; six studies, 657 participants). The funnel plot for health-related quality of life was asymmetrical, favouring no therapy, and the funnel plot for fatigue was roughly symmetrical. This hints at overall low risk of publication bias. Yoga did not appear to reduce depression (pooled SMD -0.13, 95% CI -0.31 to 0.05; seven studies, 496 participants; low-quality evidence) or anxiety (pooled SMD -0.53, 95% CI -1.10 to 0.04; six studies, 346 participants; very low-quality evidence) in the short term and had no medium-term effects on health-related quality of life (pooled SMD 0.10, 95% CI -0.23 to 0.42; two studies, 146 participants; low-quality evidence) or fatigue (pooled SMD -0.04, 95% CI -0.36 to 0.29; two studies, 146 participants; low-quality evidence). Investigators reported no serious adverse events.Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce

  3. Total hip arthroplasty after a previous pelvic osteotomy: A systematic review and meta-analysis.

    Science.gov (United States)

    Shigemura, T; Yamamoto, Y; Murata, Y; Sato, T; Tsuchiya, R; Wada, Y

    2018-06-01

    There are several reports regarding total hip arthroplasty (THA) after a previous pelvic osteotomy (PO). However, to our knowledge, until now there has been no formal systematic review and meta-analysis published to summarize the clinical results of THA after a previous PO. Therefore, we conducted a systematic review and meta-analysis of results of THA after a previous PO. We focus on these questions as follows: does a previous PO affect the results of subsequent THA, such as clinical outcomes, operative time, operative blood loss, and radiological parameters. Using PubMed, Web of Science, and Cochrane Library, we searched for relevant original papers. The pooling of data was performed using RevMan software (version 5.3, Cochrane Collaboration, Oxford, UK). A p-value50%, significant heterogeneity was assumed and a random-effects model was applied for the meta-analysis. A fixed-effects model was applied in the absence of significant heterogeneity. Eleven studies were included in this meta-analysis. The pooled results indicated that there was no significant difference in postoperative Merle D'Aubigne-Postel score (I 2 =0%, SMD=-0.15, 95% CI: -0.36 to 0.06, p=0.17), postoperative Harris hip score (I 2 =60%, SMD=-0.23, 95% CI: -0.50 to 0.05, p=0.10), operative time (I 2 =86%, SMD=0.37, 95% CI: -0.09 to 0.82, p=0.11), operative blood loss (I 2 =82%, SMD=0.23, 95% CI: -0.17 to 0.63, p=0.25), and cup abduction angle (I 2 =43%, SMD=-0.08, 95% CI: -0.25 to 0.09, p=0.38) between THA with and without a previous PO. However, cup anteversion angle of THA with a previous PO was significantly smaller than that of without a previous PO (I 2 =77%, SMD=-0.63, 95% CI: -1.13 to -0.13, p=0.01). Systematic review and meta-analysis of results of THA after a previous PO was performed. A previous PO did not affect the results of subsequent THA, except for cup anteversion. Because of the low quality evidence currently available, high-quality randomized controlled trials are required

  4. A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids effects on inflammatory markers in colorectal cancer.

    Science.gov (United States)

    Mocellin, Michel C; Camargo, Carolina Q; Nunes, Everson Araujo; Fiates, Giovanna M R; Trindade, Erasmo B S M

    2016-04-01

    Cancer and inflammation are closely related and an exacerbated inflammatory process can lead to tumor progression and a worse prognosis for the patient with cancer. Scientific literature has shown evidence that n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory action, and for this reason could be useful as an adjuvant in the treatment of some cancers. A systematic review and meta-analysis of the literature was conducted until September, 2014, to evaluate the effects of n-3 PUFA on inflammatory mediators in colorectal cancer (CRC) patients. Clinical trials were systematically searched in three electronic databases and screening reference lists. Random meta-analysis model was used to calculate the overall and stratified effect sizes. Nine trials, representing 475 patients with CRC, evaluated effects of n-3 PUFA on cytokines (n = 6) and/or acute phase proteins (n = 5) levels. n-3 PUFA reduce the levels of IL-6 (SMD -2.34; 95% CI -4.37, -0.31; p = 0.024) and increase albumin (SMD 0.31; 95% CI 0.06, 0.56; p = 0.014) in overall analyses. In stratified analyses, reduction in IL-6 levels occurs in surgical patients that received 0.2 g/kg of fish oil parenterally at postoperative period (SMD -0.65; 95% CI -1.06, -0.24; p = 0.002), while, increase in albumin concentration occurs in surgical patients that received ≥ 2.5 g/d of EPA + DHA orally at preoperative period (SMD 0.34; 95% CI 0.02, 0.66; p = 0.038). In patients undergoing chemotherapy, the supplementation of 0.6 g/d of EPA + DHA during 9 week reduces CRP levels (SMD -0.95; 95% CI -1.73, -0.17; p = 0.017), and CRP/albumin ratio (SMD -0.95; 95% CI -1.73, -0.18; p = 0.016). The results suggest benefits on some inflammatory mediators with the use of n-3 PUFA on CRC patients, but these benefits are specific to certain supplementation protocols involving duration, dose and route of administration, and also, the concomitant anti-cancer treatment adopted. Copyright © 2015 Elsevier Ltd and

  5. Reference Evapotranspiration Retrievals from a Mesoscale Model Based Weather Variables for Soil Moisture Deficit Estimation

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    Prashant K. Srivastava

    2017-10-01

    Full Text Available Reference Evapotranspiration (ETo and soil moisture deficit (SMD are vital for understanding the hydrological processes, particularly in the context of sustainable water use efficiency in the globe. Precise estimation of ETo and SMD are required for developing appropriate forecasting systems, in hydrological modeling and also in precision agriculture. In this study, the surface temperature downscaled from Weather Research and Forecasting (WRF model is used to estimate ETo using the boundary conditions that are provided by the European Center for Medium Range Weather Forecast (ECMWF. In order to understand the performance, the Hamon’s method is employed to estimate the ETo using the temperature from meteorological station and WRF derived variables. After estimating the ETo, a range of linear and non-linear models is utilized to retrieve SMD. The performance statistics such as RMSE, %Bias, and Nash Sutcliffe Efficiency (NSE indicates that the exponential model (RMSE = 0.226; %Bias = −0.077; NSE = 0.616 is efficient for SMD estimation by using the Observed ETo in comparison to the other linear and non-linear models (RMSE range = 0.019–0.667; %Bias range = 2.821–6.894; NSE = 0.013–0.419 used in this study. On the other hand, in the scenario where SMD is estimated using WRF downscaled meteorological variables based ETo, the linear model is found promising (RMSE = 0.017; %Bias = 5.280; NSE = 0.448 as compared to the non-linear models (RMSE range = 0.022–0.707; %Bias range = −0.207–−6.088; NSE range = 0.013–0.149. Our findings also suggest that all the models are performing better during the growing season (RMSE range = 0.024–0.025; %Bias range = −4.982–−3.431; r = 0.245–0.281 than the non−growing season (RMSE range = 0.011–0.12; %Bias range = 33.073–32.701; r = 0.161–0.244 for SMD estimation.

  6. The Effects of Traditional Chinese Exercise in Treating Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yingjie Zhang

    Full Text Available Traditional Chinese exercise (TCE includes a variety of exercise, which is being accepted by more and more people in the treatment of knee osteoarthritis (OA from different countries. With the attendant, many clinical reports focus on it. Our meta-analysis aimed to systematically assess the effects of traditional Chinese exercise on pain, stiffness, physical function, quality of life, mental health and adverse events in people with knee osteoarthritis.PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL, the Web of Science, and Chinese Biomedical Literature Database (CBM were searched from the time of their inception through April 2016 and risk of bias was independently assessed by two authors. Outcome measures included pain, physical functional, joint stiffness, quality of life, mental health and safety. For pooled outcomes, standardized mean differences (SMD and 95% confidence intervals (CI were calculated.Eight randomized controlled trials with a sample size of 375 cases met the criteria to be included in the study indicating that high quality literature is lacking in this field. Results of the meta-analysis showed that short-term TCE could relieve pain (SMD: -0.77;95% CI: -1.13 to -0.41; P<0.0001, improve physical function (SMD -0.75; 95% CI: -0.98 to -0.52; P<0.00001, and alleviate stiffness (SMD: -0.56; 95%: CI -0.96 to -0.16; P<0.006, but had no significant effect on quality of life (SMD: 0.57; 95% CI: 0.17 to 0.97; P = 0.005, and mental health (SMD 4.12; 95% CI: -0.50 to 8.73; P = 0.08. Moreover, TCE was not associated with serious adverse events.Our systematic review revealed that short-term TCE was potentially beneficial in terms of reducing pain, improving physical function and alleviating stiffness. These results may suggest that TCE could prove useful as an adjuvant treatment for patients with knee OA. Further studies are urgently needed to confirm these results.

  7. Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta-analysis.

    Science.gov (United States)

    Beumer, Lucy; Wong, Jennie; Warden, Stuart J; Kemp, Joanne L; Foster, Paul; Crossley, Kay M

    2016-04-01

    To explore the effects of exercise (water-based or land-based) and/or manual therapies on pain in adults with clinically and/or radiographically diagnosed hip osteoarthritis (OA). A systematic review and meta-analysis was performed, with patient reported pain assessed using a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Data were grouped by follow-up time (0-3 months=short term; 4-12 months=medium term and; >12 months=long term), and standardised mean differences (SMD) with 95% CIs were used to establish intervention effect sizes. Study quality was assessed using modified PEDro scores. 19 trials were included. Four studies showed short-term benefits favouring water-based exercise over minimal control using the WOMAC pain subscale (SMD -0.53, 95% CI -0.96 to -0.10). Six studies supported a short-term benefit of land-based exercise compared to minimal control on VAS assessed pain (SMD -0.49, 95% CI -0.70 to -0.29). There were no medium (SMD -0.23, 95% CI -0.48 to 0.03) or long (SMD -0.22, 95% CI -0.51 to 0.06) term benefits of exercise therapy, or benefit of combining exercise therapy with manual therapy (SMD -0.38, 95% CI -0.88 to 0.13) when compared to minimal control. Best available evidence indicates that exercise therapy (whether land-based or water-based) is more effective than minimal control in managing pain associated with hip OA in the short term. Larger high-quality RCTs are needed to establish the effectiveness of exercise and manual therapies in the medium and long term. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Quantification of sauter mean diameter in diesel sprays using scattering-absorption extinction measurements

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Gabrielle L; Magnotti, Gina M; Knox, Benjamin W; Genzale, Caroline L; Matusik, Katarzyna E; Duke, Daniel J; Powell, Christopher F; Kastengren, Alan L

    2017-05-18

    Quantitative measurements of the primary breakup process in diesel sprays are lacking due to a range of experimental and diagnostic challenges, including: high droplet number density environments, very small characteristic drop size scales (~1-10 μm), and high characteristic velocities in the primary breakup region (~600 m/s). Due to these challenges, existing measurement techniques have failed to resolve a sufficient range of the temporal and spatial scales involved and much remains unknown about the primary atomization process in practical diesel sprays. To gain a better insight into this process, we have developed a joint visible and x-ray extinction measurement technique to quantify axial and radial distributions of the path-integrated Sauter Mean Diameter (SMD) and Liquid Volume Fraction (LVF) for diesel-like sprays. This technique enables measurement of the SMD in regions of moderate droplet number density, enabling construction of the temporal history of drop size development within practical diesel sprays. The experimental campaign was conducted jointly at the Georgia Institute of Technology and Argonne National Laboratory using the Engine Combustion Network “Spray D” injector. X-ray radiography liquid absorption measurements, conducted at the Advanced Photon Source at Argonne, quantify the liquid-fuel mass and volume distribution in the spray. Diffused back-illumination liquid scattering measurements were conducted at Georgia Tech to quantify the optical thickness throughout the spray. By application of Mie-scatter equations, the ratio of the absorption and scattering extinction measurements is demonstrated to yield solutions for the SMD. This work introduces the newly developed scattering-absorption measurement technique and highlights the important considerations that must be taken into account when jointly processing these measurements to extract the SMD. These considerations include co-alignment of measurements taken at different institutions

  9. Serum uric acid levels in patients with Parkinson's disease: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Min Wen

    Full Text Available Lower serum uric acid (UA levels have been reported as a risk factor in Parkinson's disease (PD. However, the results have been inconsistent so far.The aim of the present study was to clarify the potential relationship of uric acid with PD.Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs with 95% confidence intervals (CIs. Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0.Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001 and these results showed no geographic regional (Asia: SMD = -0.65, 95% CI [-0.84, -0.46], Z = 6.75, p <0.001; Non-Asia: SMD = -0.25, 95% CI [-0.43, -0.07], Z = 2.70, p = 0.007 and sex differences (women: SMD = -0.53, 95% CI [-0.70, -0.35], z = 5.98, p <0.001; men: SMD = -0.66, 95% CI [-0.87, -0.44], z = 6.03, p <0.001. Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001.Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate

  10. Meta-analytic methods for pooling rates when follow-up duration varies: a case study

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    Wolf Fredric M

    2004-07-01

    Full Text Available Abstract Background Meta-analysis can be used to pool rate measures across studies, but challenges arise when follow-up duration varies. Our objective was to compare different statistical approaches for pooling count data of varying follow-up times in terms of estimates of effect, precision, and clinical interpretability. Methods We examined data from a published Cochrane Review of asthma self-management education in children. We selected two rate measures with the largest number of contributing studies: school absences and emergency room (ER visits. We estimated fixed- and random-effects standardized weighted mean differences (SMD, stratified incidence rate differences (IRD, and stratified incidence rate ratios (IRR. We also fit Poisson regression models, which allowed for further adjustment for clustering by study. Results For both outcomes, all methods gave qualitatively similar estimates of effect in favor of the intervention. For school absences, SMD showed modest results in favor of the intervention (SMD -0.14, 95% CI -0.23 to -0.04. IRD implied that the intervention reduced school absences by 1.8 days per year (IRD -0.15 days/child-month, 95% CI -0.19 to -0.11, while IRR suggested a 14% reduction in absences (IRR 0.86, 95% CI 0.83 to 0.90. For ER visits, SMD showed a modest benefit in favor of the intervention (SMD -0.27, 95% CI: -0.45 to -0.09. IRD implied that the intervention reduced ER visits by 1 visit every 2 years (IRD -0.04 visits/child-month, 95% CI: -0.05 to -0.03, while IRR suggested a 34% reduction in ER visits (IRR 0.66, 95% CI 0.59 to 0.74. In Poisson models, adjustment for clustering lowered the precision of the estimates relative to stratified IRR results. For ER visits but not school absences, failure to incorporate study indicators resulted in a different estimate of effect (unadjusted IRR 0.77, 95% CI 0.59 to 0.99. Conclusions Choice of method among the ones presented had little effect on inference but affected the

  11. Meta-analytic methods for pooling rates when follow-up duration varies: a case study.

    Science.gov (United States)

    Guevara, James P; Berlin, Jesse A; Wolf, Fredric M

    2004-07-12

    Meta-analysis can be used to pool rate measures across studies, but challenges arise when follow-up duration varies. Our objective was to compare different statistical approaches for pooling count data of varying follow-up times in terms of estimates of effect, precision, and clinical interpretability. We examined data from a published Cochrane Review of asthma self-management education in children. We selected two rate measures with the largest number of contributing studies: school absences and emergency room (ER) visits. We estimated fixed- and random-effects standardized weighted mean differences (SMD), stratified incidence rate differences (IRD), and stratified incidence rate ratios (IRR). We also fit Poisson regression models, which allowed for further adjustment for clustering by study. For both outcomes, all methods gave qualitatively similar estimates of effect in favor of the intervention. For school absences, SMD showed modest results in favor of the intervention (SMD -0.14, 95% CI -0.23 to -0.04). IRD implied that the intervention reduced school absences by 1.8 days per year (IRD -0.15 days/child-month, 95% CI -0.19 to -0.11), while IRR suggested a 14% reduction in absences (IRR 0.86, 95% CI 0.83 to 0.90). For ER visits, SMD showed a modest benefit in favor of the intervention (SMD -0.27, 95% CI: -0.45 to -0.09). IRD implied that the intervention reduced ER visits by 1 visit every 2 years (IRD -0.04 visits/child-month, 95% CI: -0.05 to -0.03), while IRR suggested a 34% reduction in ER visits (IRR 0.66, 95% CI 0.59 to 0.74). In Poisson models, adjustment for clustering lowered the precision of the estimates relative to stratified IRR results. For ER visits but not school absences, failure to incorporate study indicators resulted in a different estimate of effect (unadjusted IRR 0.77, 95% CI 0.59 to 0.99). Choice of method among the ones presented had little effect on inference but affected the clinical interpretability of the findings. Incidence rate

  12. Baseline and postoperative levels of C-reactive protein and interleukins as inflammatory predictors of atrial fibrillation following cardiac surgery: a systematic review and meta-analysis.

    Science.gov (United States)

    Weymann, Alexander; Popov, Aron-Frederik; Sabashnikov, Anton; Ali-Hasan-Al-Saegh, Sadeq; Ryazanov, Mikhail; Tse, Gary; Mirhosseini, Seyed Jalil; Liu, Tong; Lotfaliani, Mohammadreza; Sedaghat, Meghdad; Baker, William L; Ghanei, Azam; Yavuz, Senol; Zeriouh, Mohamed; Izadpanah, Payman; Dehghan, Hamidreza; Testa, Luca; Nikfard, Maryam; Sá, Michel Pompeu Barros de Oliveira; Mashhour, Ahmed; Nombela-Franco, Luis; Rezaeisadrabadi, Mohammad; D'Ascenzo, Fabrizio; Zhigalov, Konstantin; Benedetto, Umberto; Aminolsharieh Najafi, Soroosh; Szczechowicz, Marcin; Roever, Leonardo; Meng, Lei; Gong, Mengqi; Deshmukh, Abhishek J; Palmerini, Tullio; Linde, Cecilia; Filipiak, Krzysztof J; Stone, Gregg W; Biondi-Zoccai, Giuseppe; Calkins, Hugh

    2018-01-01

    Postoperative atrial fibrillation (POAF) is a leading arrhythmia with high incidence and serious clinical implications after cardiac surgery. Cardiac surgery is associated with systemic inflammatory response including increase in cytokines and activation of endothelial and leukocyte responses. This systematic review and meta-analysis aimed to determine the strength of evidence for evaluating the association of inflammatory markers, such as C-reactive protein (CRP) and interleukins (IL), with POAF following isolated coronary artery bypass grafting (CABG), isolated valvular surgery, or a combination of these procedures. We conducted a meta-analysis of studies evaluating measured baseline (from one week before surgical procedures) and postoperative levels (until one week after surgical procedures) of inflammatory markers in patients with POAF. A compre-hensive search was performed in electronic medical databases (Medline/PubMed, Web of Science, Embase, Science Direct, and Google Scholar) from their inception through May 2017 to identify relevant studies. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. A literature search of all major databases retrieved 1014 studies. After screening, 42 studies were analysed including a total of 8398 patients. Pooled analysis showed baseline levels of CRP (standard mean difference [SMD] 0.457 mg/L, p < 0.001), baseline levels of IL-6 (SMD 0.398 pg/mL, p < 0.001), postoperative levels of CRP (SMD 0.576 mg/L, p < 0.001), postoperative levels of IL-6 (SMD 1.66 pg/mL, p < 0.001), postoperative levels of IL-8 (SMD 0.839 pg/mL, p < 0.001), and postoperative levels of IL-10 (SMD 0.590 pg/mL, p < 0.001) to be relevant inflammatory parameters significantly associated with POAF. Perioperative inflammation is proposed to be involved in the pathogenesis of POAF. Therefore, perioperative assessment of CRP, IL-6, IL-8, and IL-10 can help clinicians in terms of predicting and monitoring for POAF.

  13. Dietary toxicity of soluble and insoluble molybdenum to northern bobwhite quail (Colinus virginianus).

    Science.gov (United States)

    Stafford, Jennifer M; Lambert, Charles E; Zyskowski, Justin A; Engfehr, Cheryl L; Fletcher, Oscar J; Clark, Shanna L; Tiwary, Asheesh; Gulde, Cynthia M; Sample, Bradley E

    2016-03-01

    Limited data are available on the effects of molybdenum (Mo) on avian wildlife, which impairs evaluation of ecological exposure and risk. While Mo is an essential trace nutrient in birds, little is known of its toxicity to birds exposed to molybdenum disulfide (MoS2), the predominant form found in molybdenite ore. The chemical form and bioavailability of Mo is important in determining its toxicity. Avian toxicity tests typically involve a soluble form of Mo, such as sodium molybdate dihydrate (SMD, Na2MoO4·2H2O); however MoS2 is generally insoluble, with low bioaccessibility under most environmental conditions. The current study monitored survival and general health (body weight and food consumption) of 9-day old northern bobwhite exposed to soluble Mo (SMD) and ore-related Mo (MoS2) in their diet for 30 days. Toxicity and bioavailability (e.g. tissue distribution) of the two Mo forms were compared. Histopathology evaluations and serum, kidney, liver, and bone tissue sample analyses were conducted. Copper, a nutrient integrally associated with Mo toxicity, was also measured in the diet and tissue. No treatment-related mortality occurred and no treatment-related lesions were recorded for either Mo form. Tissue analyses detected increased Mo concentrations in serum, kidney, liver, and bone tissues following exposure to SMD, with decreasing concentrations following a post-exposure period. For the soluble form, a No-Observed-Adverse-Effect Concentration (NOAEC) of 1200 mg Mo as SMD/kg feed (134 mg SMD/kg body weight/day) was identified based on body weight and food consumption. No adverse effects were observed in birds exposed to MoS2 at the maximum dose of 5000 mg MoS2/kg feed (545 mg MoS2/kg body weight/day). These results show that effects associated with MoS2, the more environmentally prevalent and less bioavailable Mo form, are much less than those observed for SMD. These data should support more realistic representations of exposure and risks to avian receptors

  14. Superior Effects of High-Intensity Interval Training vs. Moderate Continuous Training on Arterial Stiffness in Episodic Migraine: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Henner Hanssen

    2017-12-01

    Full Text Available Background: Migraine is associated with increased cardiovascular risk and vascular dysfunction. Since aerobic exercise can reduce cardiovascular risk, the present randomized controlled trail aimed at investigating the effects of high-intensity interval training (HIT vs. moderate continuous exercise training (MCT on arterial stiffness in migraine patients.Methods: Forty-eight episodic migraineurs were initially enrolled in the study. 37 patients [female: 30; age: 37 (SD: 10; BMI: 23.1 (5.2; Migraine days per month: 3.7 (2.5] completed the intervention. Central blood pressure, pulse wave reflection, and aortic pulse wave velocity (PWV were obtained by an oscillometric monitor. Incremental treadmill exercise testing yielded maximal and submaximal fitness parameters. Participants were randomly assigned to either HIT, MCT, or a control group (CON. The intervention groups trained twice a week over a 12-week intervention period.Results: After adjustment for between-group baseline differences, a moderate meaningful overall reduction of the augmentation index at 75 min−1 heart rate (AIx@75 was observed [partial eta squared (ηp2 = 0.16; p = 0.06]. With 91% likely beneficial effects, HIT was more effective in reducing AIx@75 than MCT [HIT: pre 22.0 (9.7, post 14.9 (13.0, standardized mean difference (SMD = 0.62; MCT: pre 16.6 (8.5, post 21.3 (10.4, SMD −0.49]. HIT induced a relevant reduction in central systolic blood pressure [cSBP: pre 118 (23 mmHg, post 110 (16 mmHg, SMD = 0.42] with a 59% possibly beneficial effect compared to CON, while MCT showed larger effects in lowering central diastolic blood pressure [pre 78 (7 mmHg, post 74 (7 mmHg, SMD = 0.61], presenting 60% possibly beneficial effects compared to CON. Central aortic PWV showed no changes in any of the three groups. Migraine days were reduced more successfully by HIT than MCT (HIT: SMD = 1.05; MCT: SMD = 0.43.Conclusion: HIT but not MCT reduces AIx@75 as a measure of pulse wave

  15. The Role of Pathogenic Autoantibodies in Autoimmunity

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    Merrill J. Rowley

    2015-11-01

    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  16. PM1-Alpha ELISA: the assay of choice for the detection of anti-PM/Scl autoantibodies?

    Science.gov (United States)

    Mahler, Michael; Fritzler, Marvin J

    2009-03-01

    A characteristic serological feature of patients suffering from the overlap polymyositis and scleroderma (PM/Scl) syndrome are antibodies to the human counterpart of the yeast exosome referred to as the PM/Scl complex. Historically, the detection of anti-PM/Scl antibodies was laborious and relied largely on indirect immunofluorescence and immunodiffusion techniques. In 1992 the major autoantigen PM/Scl-100 was identified and cloned. Subsequently, the major epitopes were mapped and one of these, termed PM1-Alpha, became the antigen for a novel ELISA exhibiting high sensitivity and specificity for the detection of anti-PM/Scl antibodies. Comparative studies with other methods using other PM/Scl autoantigens have shown that the PM1-Alpha ELISA has higher sensitivity and specificity than assays that employed recombinant PM/Scl-75c and PM/Scl-100. Anti-PM1-Alpha antibodies were identified in 55.0% of sera from PM/Scl overlap syndrome patients, but were also seen in 7.9% of SSc and in 7.5% of PM patients. The frequency in other systemic autoimmune diseases and in infectious diseases was significant lower. In summary, the data derived from individual studies suggest that PM1-Alpha may become the "gold standard" for the detection of anti-PM/Scl antibodies.

  17. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

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    Satoko Arai

    2013-04-01

    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  18. Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity.

    Science.gov (United States)

    Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda

    2013-10-01

    Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

  19. The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/- mice.

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    Peter M Mihailovic

    Full Text Available Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/- mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/- mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/- with different doses of the shortened peptide (Cramp resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs, whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/- mouse model.

  20. Role of immune system in type 1 diabetes mellitus pathogenesis.

    Science.gov (United States)

    Szablewski, Leszek

    2014-09-01

    The immune system is the body's natural defense system against invading pathogens. It protects the body from infection and works to communicate an individual's well-being through a complex network of interconnected cells and cytokines. This system is an associated host defense. An uncontrolled immune system has the potential to trigger negative complications in the host. Type 1 diabetes results from the destruction of pancreatic β-cells by a β-cell-specific autoimmune process. Examples of β-cell autoantigens are insulin, glutamic acid decarboxylase, tyrosine phosphatase, and insulinoma antigen. There are many autoimmune diseases, but type 1 diabetes mellitus is one of the well-characterized autoimmune diseases. The mechanisms involved in the β-cell destruction are still not clear; it is generally believed that β-cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes are involved in the β-cell-specific autoimmune process. It is necessary to determine what exact factors are causing the immune system to become unregulated in such a manner as to promote an autoimmune response. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Londei, M.; Savill, C.M.; Verhoef, A.; Brennan, F.; Leech, Z.A.; Feldmann, M.; Duance, V.; Maini, R.N.

    1989-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis

  2. Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides

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    Peter Lamprecht

    2018-04-01

    Full Text Available Anti-neutrophil cytoplasmic autoantibodies (ANCA targeting proteinase 3 (PR3 and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

  3. The Pathogenesis of Lupus Nephritis

    Science.gov (United States)

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  4. Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

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    A. Hanyecz

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA, and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.

  5. Autoimmunity due to molecular mimicry as a cause of neurological disease.

    Science.gov (United States)

    Levin, Michael C; Lee, Sang Min; Kalume, Franck; Morcos, Yvette; Dohan, F Curtis; Hasty, Karen A; Callaway, Joseph C; Zunt, Joseph; Desiderio, Dominic; Stuart, John M

    2002-05-01

    One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.

  6. The Emerging Importance of Non-HLA Autoantibodies in Kidney Transplant Complications.

    Science.gov (United States)

    Cardinal, Héloise; Dieudé, Mélanie; Hébert, Marie-Josée

    2017-02-01

    Antibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular injury, and/or rejection creates permissive conditions for the expression of cryptic autoantigens, allowing these autoantibodies to bind antigenic targets and further enhance vascular inflammation and renal dysfunction. Antiperlecan/LG3 antibodies and antiangiotensin II type 1 receptor antibodies have been found before transplant in patients with de novo transplants and portend negative long-term outcome in patients with renal transplants. Here, we review mounting evidence suggesting an important role for autoantibodies to cryptic antigens as novel accelerators of kidney dysfunction and acute or chronic allograft rejection. Copyright © 2017 by the American Society of Nephrology.

  7. Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis

    Science.gov (United States)

    Brooks, Wesley H.

    2017-01-01

    Viruses are suspected of significant roles in autoimmune diseases but the mechanisms are unclear. We get some insight by considering demands a virus places on host cells. Viruses not only require production of their own proteins, RNA and/or DNA, but also production of additional cellular machinery, such as ribosomes, to handle the increased demands. Since the nucleolus is a major site of RNA processing and ribonucleoprotein assembly, nucleoli are targeted by viruses, directly when viral RNA and proteins enter the nucleolus and indirectly when viruses induce increased expression of cellular polyamine genes. Polyamines are at high levels in nucleoli to assist in RNA folding. The size and activity of nucleoli increase directly with increases in polyamines. Nucleolar expansion due to abnormal increases in polyamines could disrupt nearby chromatin, such as the inactive X chromosome, leading to expression of previously sequestered DNA. Sudden expression of a large concentration of Alu elements from the disrupted inactive X can compete with RNA transcripts containing intronic Alu sequences that normally maintain nucleolar structural integrity. Such disruption of nucleolar activity can lead to misfolded RNAs, misassembled ribonucleoprotein complexes, and fragmentation of the nucleolus. Many autoantigens in lupus are, at least transiently, components of the nucleolus. Considering these effects of viruses, the “X chromosome–nucleolus nexus” hypothesis, which proposed disruption of the inactive X by the nucleolus during stress, is now expanded here to propose subsequent disruption of the nucleolus by previously sequestered Alu elements, which can fragment the nucleolus, leading to generation of autoantigens. PMID:29234321

  8. The value of the Widal test in the diagnosis of Prolonged Septicemic Salmonellosis

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    José Roberto Lambertucci

    1985-04-01

    Full Text Available Twenty patients with prolonged septicemic salmonellosis (Group 1 and 20 with schistosomiasis mansoni (Group 2 were selected for this study. In both groups, the Widal test was done using antigens of the sample Ty 901 (S. typhi. The test was also applied in 6 group 1 patients with antigens prepared from salmonellae isolated from these patients (autoantigens. Titres over 1:200 were considered significant. Ten group 1 patients (50% were positive for antigen "H" and 5 (25% were positive for antigen "O". Three patients with negative "H" and "O" reactions became positive with high titres when using autoantigens. Two other cases maintained the same positive titres and one case showed a fourfold increase in titres when the test was done 'with antigens of the Salmonella isolated. The Widal test was positive in most patients infected with group D Salmonellae. Considering titres above 1:200, all cases were negative in Group 2. The authors conclude that the Widal test has low positivity in prolonged septicemic salmonellosis. The test may be valuable in the diagnosis of this disease when using S. paratyphi "A" and "B" antigens and a mixture of Salmonella antigens taken from other groups.

  9. [Antibodies and physiopathogeny of autoimmune hepatitis].

    Science.gov (United States)

    García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo

    2003-01-01

    Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

  10. Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2011-01-01

    Full Text Available Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

  11. Effects of Supervised vs. Unsupervised Training Programs on Balance and Muscle Strength in Older Adults: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lacroix, André; Hortobágyi, Tibor; Beurskens, Rainer; Granacher, Urs

    2017-11-01

    Balance and resistance training can improve healthy older adults' balance and muscle strength. Delivering such exercise programs at home without supervision may facilitate participation for older adults because they do not have to leave their homes. To date, no systematic literature analysis has been conducted to determine if supervision affects the effectiveness of these programs to improve healthy older adults' balance and muscle strength/power. The objective of this systematic review and meta-analysis was to quantify the effectiveness of supervised vs. unsupervised balance and/or resistance training programs on measures of balance and muscle strength/power in healthy older adults. In addition, the impact of supervision on training-induced adaptive processes was evaluated in the form of dose-response relationships by analyzing randomized controlled trials that compared supervised with unsupervised trials. A computerized systematic literature search was performed in the electronic databases PubMed, Web of Science, and SportDiscus to detect articles examining the role of supervision in balance and/or resistance training in older adults. The initially identified 6041 articles were systematically screened. Studies were included if they examined balance and/or resistance training in adults aged ≥65 years with no relevant diseases and registered at least one behavioral balance (e.g., time during single leg stance) and/or muscle strength/power outcome (e.g., time for 5-Times-Chair-Rise-Test). Finally, 11 studies were eligible for inclusion in this meta-analysis. Weighted mean standardized mean differences between subjects (SMD bs ) of supervised vs. unsupervised balance/resistance training studies were calculated. The included studies were coded for the following variables: number of participants, sex, age, number and type of interventions, type of balance/strength tests, and change (%) from pre- to post-intervention values. Additionally, we coded training according

  12. The bactericidal effect of surface micro-discharge plasma under different ambient conditions

    International Nuclear Information System (INIS)

    Shimizu, T; Zimmermann, J L; Morfill, G E

    2011-01-01

    A series of experiments on the bactericidal properties of plasmas using a surface micro-discharge (SMD) device in an atmosphere under different ambient temperatures and humidities was carried out. This plasma dispenser was developed for use as a disinfection system in private and public places (hospitals, medical practices, etc). The bactericidal effect is due to the interplay of the plasma and the chemical products produced via interactions with O 2 /N 2 and H 2 O vapour in air. To use this device in different countries and therefore under various ambient conditions, it is important to understand its behaviour and efficiency, especially with respect to air temperature and humidity. The experimental results obtained in this study show that the bactericidal properties of the SMD plasma dispenser are not sensitive to the different temperatures and humidities.

  13. The bactericidal effect of surface micro-discharge plasma under different ambient conditions

    Science.gov (United States)

    Shimizu, T.; Zimmermann, J. L.; Morfill, G. E.

    2011-02-01

    A series of experiments on the bactericidal properties of plasmas using a surface micro-discharge (SMD) device in an atmosphere under different ambient temperatures and humidities was carried out. This plasma dispenser was developed for use as a disinfection system in private and public places (hospitals, medical practices, etc). The bactericidal effect is due to the interplay of the plasma and the chemical products produced via interactions with O2/N2 and H2O vapour in air. To use this device in different countries and therefore under various ambient conditions, it is important to understand its behaviour and efficiency, especially with respect to air temperature and humidity. The experimental results obtained in this study show that the bactericidal properties of the SMD plasma dispenser are not sensitive to the different temperatures and humidities.

  14. Framing of health information messages.

    Science.gov (United States)

    Akl, Elie A; Oxman, Andrew D; Herrin, Jeph; Vist, Gunn E; Terrenato, Irene; Sperati, Francesca; Costiniuk, Cecilia; Blank, Diana; Schünemann, Holger

    2011-12-07

    The same information about the evidence on health effects can be framed either in positive words or in negative words. Some research suggests that positive versus negative framing can lead to different decisions, a phenomenon described as the framing effect. Attribute framing is the positive versus negative description of a specific attribute of a single item or a state, for example, "the chance of survival with cancer is 2/3" versus "the chance of mortality with cancer is 1/3". Goal framing is the description of the consequences of performing or not performing an act as a gain versus a loss, for example, "if you undergo a screening test for cancer, your survival will be prolonged" versus "if you don't undergo screening test for cancer, your survival will be shortened". To evaluate the effects of attribute (positive versus negative) framing and of goal (gain versus loss) framing of the same health information, on understanding, perception of effectiveness, persuasiveness, and behavior of health professionals, policy makers, and consumers. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, issue 3 2007), MEDLINE (Ovid) (1966 to October 2007), EMBASE (Ovid) (1980 to October 2007), PsycINFO (Ovid) (1887 to October 2007). There were no language restrictions. We reviewed the reference lists of related systematic reviews, included studies and of excluded but closely related studies. We also contacted experts in the field. We included randomized controlled trials, quasi-randomised controlled trials, and cross-over studies with health professionals, policy makers, and consumers evaluating one of the two types of framing. Two review authors extracted data in duplicate and independently. We graded the quality of evidence for each outcome using the GRADE approach. We standardized the outcome effects using standardized mean difference (SMD). We stratified the analysis by the type of framing (attribute, goal) and conducted pre

  15. Correlation between serum interleukin-6 level and type 1 diabetes mellitus: A systematic review and meta-analysis.

    Science.gov (United States)

    Chen, Yin-Ling; Qiao, Yong-Chao; Pan, Yan-Hong; Xu, Yan; Huang, Yong-Cheng; Wang, Yin-Hui; Geng, Li-Jun; Zhao, Hai-Lu; Zhang, Xiao-Xi

    2017-06-01

    This report aimed to explore the association between the change of circulating interleukin-6 (IL-6) in patients and the development of type 1 diabetes mellitus (T1DM). Four databases (PubMed, CNKI, WanFang and Civip) were used to search and list all clinical case-control studies about serum IL-6 level in T1DM patients between Jan 1, 2000 and Aug 31, 2016. A total of 20 case-control studies with 1238 T1DM patients and 742 healthy controls were included in this study. Compared to healthy controls, the serum content of IL-6 in patients with T1DM was significantly greater (overall: SMD, 1.49; 95% CI, 1.04 to 1.93; pAmerican group (SMD, 1.68; 95% CI, 0.85-2.51; pdiabetes mellitus. Copyright © 2017. Published by Elsevier Ltd.

  16. Erythropoietin levels in patients with sleep apnea: a meta-analysis.

    Science.gov (United States)

    Zhang, Xiao-Bin; Zeng, Yi-Ming; Zeng, Hui-Qing; Zhang, Hua-Ping; Wang, Hui-Ling

    2017-06-01

    Currently available data regarding the blood levels of erythropoietin (EPO) in sleep apnea (SA) patients are contradictory. The aim of the present meta-analysis was to evaluate the EPO levels in SA patients via quantitative analysis. A systematic search of Pubmed, Embase, and Web of Science were performed. EPO levels in SA group and control group were extracted from each eligible study. Weight mean difference (WMD) or Standard mean difference (SMD) with 95% confidence interval (CI) was calculated by using fixed-effects or random effect model analysis according to the degree of heterogeneity between studies. A total of 9 studies involving 407 participants were enrolled. The results indicated that EPO levels in SA group were significantly higher than that in control group (SMD 0.61, 95% CI 0.11-1.11, p = 0.016). Significantly higher EPO levels were found in patients with body mass index analysis (both p analysis.

  17. A Vision for the Exploration of Mars: Robotic Precursors Followed by Humans to Mars Orbit in 2033

    Science.gov (United States)

    Sellers, Piers J.; Garvin, James B.; Kinney, Anne L.; Amato, Michael J.; White, Nicholas E.

    2012-01-01

    The reformulation of the Mars program gives NASA a rare opportunity to deliver a credible vision in which humans, robots, and advancements in information technology combine to open the deep space frontier to Mars. There is a broad challenge in the reformulation of the Mars exploration program that truly sets the stage for: 'a strategic collaboration between the Science Mission Directorate (SMD), the Human Exploration and Operations Mission Directorate (HEOMD) and the Office of the Chief Technologist, for the next several decades of exploring Mars'.Any strategy that links all three challenge areas listed into a true long term strategic program necessitates discussion. NASA's SMD and HEOMD should accept the President's challenge and vision by developing an integrated program that will enable a human expedition to Mars orbit in 2033 with the goal of returning samples suitable for addressing the question of whether life exists or ever existed on Mars

  18. Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury.

    Science.gov (United States)

    Saghazadeh, Amene; Rezaei, Nima

    2017-10-03

    Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that affects cognitive and higher cognitive functions. Increasing prevalence of ASD and high rates of related comorbidities has caused serious health loss and placed an onerous burden on the supporting families, caregivers, and health care services. Heavy metals are among environmental factors that may contribute to ASD. However, due to inconsistencies across studies, it is still hard to explain the association between ASD and toxic metals. Therefore the objective of this study was to investigate the difference in heavy metal measures between patients with ASD and control subjects. We included observational studies that measured levels of toxic metals (antimony, arsenic, cadmium, lead, manganese, mercury, nickel, silver, and thallium) in different specimens (whole blood, plasma, serum, red cells, hair and urine) for patients with ASD and for controls. The main electronic medical database (PubMed and Scopus) were searched from inception through October 2016. 52 studies were eligible to be included in the present systematic review, of which 48 studies were included in the meta-analyses. The hair concentrations of antimony (standardized mean difference (SMD)=0.24; 95% confidence interval (CI): 0.03 to 0.45) and lead (SMD=0.60; 95% confidence interval (CI): 0.17 to 1.03) in ASD patients were significantly higher than those of control subjects. ASD patients had higher erythrocyte levels of lead (SMD=1.55, CI: 0.2 to 2.89) and mercury (SMD=1.56, CI: 0.42 to 2.70). There were significantly higher blood lead levels in ASD patients (SMD=0.43, CI: 0.02 to 0.85). Sensitivity analyses showed that ASD patients in developed but not in developing countries have lower hair concentrations of cadmium (SMD=-0.29, CI: -0.46 to -0.12). Also, such analyses indicated that ASD patients in developing but not in developed lands have higher hair concentrations of lead (SMD=1.58, CI: 0.80 to 2.36) and mercury (SMD=0

  19. Trend of Energy Saving in Electronic Devices for Research and Development

    Directory of Open Access Journals (Sweden)

    Rahmayanti R.

    2016-01-01

    Full Text Available In electronic industry, energy saving is one of the performance indicators of competitiveness beside price, speed, bandwidth and reliability. This affects research and development (R&D activity in mechatronic systems which uses electronic components and electronic systems. A review of trend of electronic devices technology development has been conducted with focus on energy saving. This review includes electronic devices, semiconductor, and nanotechnology. It can be concluded that the trend in electronic devices is mainly dictated by semiconductor technology development. The trend can be concluded as smaller size, lower voltage leading to energy saving, less heat, higher speed, more reliable, and cheaper. In accordance to such technology development, R&D activities in mechatronics especially in Indonesia is being pushed to make proper alignment.Some of such alignment actions are surface mount technology (SMT for installing surface mount devices components (SMD, design layout and SMD troubleshooting tools as well as human resources training and development.

  20. Preliminary Empirical Models for Predicting Shrinkage, Part Geometry and Metallurgical Aspects of Ti-6Al-4V Shaped Metal Deposition Builds

    Science.gov (United States)

    Escobar-Palafox, Gustavo; Gault, Rosemary; Ridgway, Keith

    2011-12-01

    Shaped Metal Deposition (SMD) is an additive manufacturing process which creates parts layer by layer by weld depositions. In this work, empirical models that predict part geometry (wall thickness and outer diameter) and some metallurgical aspects (i.e. surface texture, portion of finer Widmanstätten microstructure) for the SMD process were developed. The models are based on an orthogonal fractional factorial design of experiments with four factors at two levels. The factors considered were energy level (a relationship between heat source power and the rate of raw material input.), step size, programmed diameter and travel speed. The models were validated using previous builds; the prediction error for part geometry was under 11%. Several relationships between the factors and responses were identified. Current had a significant effect on wall thickness; thickness increases with increasing current. Programmed diameter had a significant effect on percentage of shrinkage; this decreased with increasing component size. Surface finish decreased with decreasing step size and current.

  1. Preliminary Empirical Models for Predicting Shrinkage, Part Geometry and Metallurgical Aspects of Ti-6Al-4V Shaped Metal Deposition Builds

    International Nuclear Information System (INIS)

    Escobar-Palafox, Gustavo; Gault, Rosemary; Ridgway, Keith

    2011-01-01

    Shaped Metal Deposition (SMD) is an additive manufacturing process which creates parts layer by layer by weld depositions. In this work, empirical models that predict part geometry (wall thickness and outer diameter) and some metallurgical aspects (i.e. surface texture, portion of finer Widmanstätten microstructure) for the SMD process were developed. The models are based on an orthogonal fractional factorial design of experiments with four factors at two levels. The factors considered were energy level (a relationship between heat source power and the rate of raw material input.), step size, programmed diameter and travel speed. The models were validated using previous builds; the prediction error for part geometry was under 11%. Several relationships between the factors and responses were identified. Current had a significant effect on wall thickness; thickness increases with increasing current. Programmed diameter had a significant effect on percentage of shrinkage; this decreased with increasing component size. Surface finish decreased with decreasing step size and current.

  2. The Distinction of Amyloid-β Protein Precursor (AβPP) Ratio in Platelet Between Alzheimer's Disease Patients and Controls: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shi, Yachen; Gu, Lihua; Alsharif, Abdul Azeez; Zhang, Zhijun

    2017-01-01

    To systematically assess the clinical significance of platelet amyloid-β protein precursor (AβPP) ratio between Alzheimer's disease (AD) patients and controls. 14 articles were selected in this analysis by search of databases including PubMed and Web of Science up to December 2016. Random effects models were used to calculate the standardized mean difference (SMD). Subgroup analyses were used to detect the cause of heterogeneity. The result showed a significant drop in platelet AβPP ratio in AD patients compared to controls [SMD: -1.871; 95% CI: (-2.33, -1.41); p analysis revealed races or the quality of studies may be the cause of high heterogeneity. This meta-analysis concluded that there is a close association between platelet AβPP ratio and AD. It is necessary to design a sizable sample study to further support that platelet AβPP ratio can be a biomarker of AD.

  3. Intra-articular bupivacaine after joint arthroplasty: a systematic review and meta-analysis of randomised placebo-controlled studies

    Science.gov (United States)

    Cui, Yang; Yang, Tuo; Zeng, Chao; Wei, Jie; Xie, Xi; Li, Liangjun; Ding, Xiang; Zhang, Yi; Lei, Guanghua

    2016-01-01

    Objectives To evaluate the efficacy and safety of intra-articular (IA) bupivacaine administered for pain relief after joint arthroplasty. Design Meta-analysis. Methods A systematic review was conducted to identify the randomised controlled trials using IA bupivacaine for postoperative pain relief from MEDLINE, Cochrane Library and EMBASE databases (up to October 2015). The standardised mean difference (SMD), the relative risk (RR) and their corresponding 95% CIs were calculated using the RevMan statistical software. Results A total of 11 randomised controlled trials were included. Statistically significant differences between IA bupivacaine and placebo were observed for the mean visual analogue scale (VAS) values (SMD −0.55; 95% CI −0.89 to −0.22; pbupivacaine after joint arthroplasty is effective for pain relief without increasing adverse effects. PMID:27406643

  4. Standardised mean difference in metaanalyses - How reliable is it in practice?

    DEFF Research Database (Denmark)

    Tendal, Britta

    The use of the standardised mean difference (SMD) is common in meta‐analyses, as it allows outcomes of a similar nature, but measured on different scales, to be combined. The application of SMDs, compared with that of the raw mean difference, can be complex. Despite this complexity, there have been...... few studies of the reliability of this effect measure in practice. The aims of this PhD were to investigate the difficulties that may arise when researchers use SMD as an effect measure and to determine the scope for reviewer bias. Three studies were undertaken in order to fulfil these aims....... In the first study, we evaluated the reproducibility of meta‐analyses using SMDs. In the second study, we determined the observer variation when extracting data for the computation of SMDs. In the third study, we investigated the range of SMDs that could be calculated based on the same outcomes from the same...

  5. The bactericidal effect of surface micro-discharge plasma under different ambient conditions

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, T; Zimmermann, J L; Morfill, G E, E-mail: tshimizu@mpe.mpg.de [Max-Planck Institute for Extraterrestrial Physics, Giessenbachstr., 85748 Garching (Germany)

    2011-02-15

    A series of experiments on the bactericidal properties of plasmas using a surface micro-discharge (SMD) device in an atmosphere under different ambient temperatures and humidities was carried out. This plasma dispenser was developed for use as a disinfection system in private and public places (hospitals, medical practices, etc). The bactericidal effect is due to the interplay of the plasma and the chemical products produced via interactions with O{sub 2}/N{sub 2} and H{sub 2}O vapour in air. To use this device in different countries and therefore under various ambient conditions, it is important to understand its behaviour and efficiency, especially with respect to air temperature and humidity. The experimental results obtained in this study show that the bactericidal properties of the SMD plasma dispenser are not sensitive to the different temperatures and humidities.

  6. Laser-Based Spatio-Temporal Characterisation of Port Fuel Injection (PFI Sprays

    Directory of Open Access Journals (Sweden)

    C. T. N. Anand

    2010-06-01

    Full Text Available In the present work, detailed laser-based diagnostic experiments were conducted to characterise the spray from low pressure 2-hole and 4-hole Port Fuel Injection (PFI injectors. The main objective of the work included obtaining quantitative information of the spatio-temporal spray structure of such low-pressure gasoline sprays. A novel approach involving a combination of techniques such as Mie scattering, Granulometry, and Laser Sheet Dropsizing (LSD was used to study the spray structure. The droplet sizes, distributions with time, Sauter Mean Diameters (SMD, droplet velocities, cone angles and spray tip penetrations of the sprays from the injectors were determined. The spray from these injectors is found to be ‘pencil like’ and not dispersed as in high pressure sprays. The application of the above mentioned techniques provides two-dimensional SMD contours of the entire spray at different instants of time, with reasonable accuracy.

  7. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments

    DEFF Research Database (Denmark)

    Altman, Roy D; Devji, Tahira; Bhandari, Mohit

    2016-01-01

    August 14th, 2014. Two reviewers assessed the eligibility of potential reports and the risk of bias of included trials. We analyzed short (≤3 months) and long-term (6-12 months) pain reduction of the saline arm of included trials using standardized mean differences (SMDs; estimated assuming a null effect...... in the meta-analysis. Based on data with moderate inconsistency IA saline was found to significantly improve short-term knee pain in 32 studies involving 1705 patients (SMD = -0.68; 95% CI: -0.78 to -0.57; P ... with saline in 19 studies involving 1445 patients (SMD = -0.61; 95% CI: -0.76 to -0.45; P

  8. The effect of mud therapy on pain relief in patients with knee osteoarthritis: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Liu, Hua; Zeng, Chao; Gao, Shu-guang; Yang, Tuo; Luo, Wei; Li, Yu-sheng; Xiong, Yi-lin; Sun, Jin-peng; Lei, Guang-hua

    2013-10-01

    A meta-analysis was conducted to examine the effect of mud therapy on pain relief in patients with knee osteoarthritis (OA). A detailed search of PubMed®/MEDLINE® was undertaken to identify randomized controlled trials and prospective comparative studies published before 9 March 2013 that compared mud therapy with control group treatments in patients with knee OA. A quantitative meta-analysis of seven studies (410 patients) was performed. There was a significant difference between the groups in the visual analogue scale pain score (standardized mean difference [SMD] -0.73) and Western Ontario and McMaster Universities Osteoarthritis Index pain score (SMD -0.30), with differences in favour of mud therapy. Mud therapy is a favourable option for pain relief in patients with knee OA. Additional high-quality randomized controlled trials need to be conducted to explore this issue further and to confirm this conclusion.

  9. The clinical value of lncRNA NEAT1 in digestive system malignancies: A comprehensive investigation based on 57 microarray and RNA-seq datasets.

    Science.gov (United States)

    Xiong, Dan-Dan; Feng, Zhen-Bo; Cen, Wei-Luan; Zeng, Jing-Jing; Liang, Lu; Tang, Rui-Xue; Gan, Xiao-Ning; Liang, Hai-Wei; Li, Zu-Yun; Chen, Gang; Luo, Dian-Zhong

    2017-03-14

    This comprehensive investigation was performed to evaluate the expression level and potential clinical value of NEAT1 in digestive system malignancies. A total of 57 lncRNA datasets of microarray or RNA-seq and 5 publications were included. The pooled standard mean deviation (SMD) indicated that NEAT1 was down-regulated in esophageal carcinoma (ESCA, SMD = -0.35, 95% CI: -0.5~-0.20, P digestive system malignancies (HR: 1.50, 95% CI: 1.28-1.76, P digestive system cancers and could be a potential diagnostic and prognostic biomarker in patients with digestive system carcinomas. Further and stricter studies with a larger number of cases are necessary to strengthen our conclusions.

  10. Planning and managing future space facility projects. [management by objectives and group dynamics

    Science.gov (United States)

    Sieber, J. E.; Wilhelm, J. A.; Tanner, T. A.; Helmreich, R. L.; Burgenbauch, S. F.

    1979-01-01

    To learn how ground-based personnel of a space project plan and organize their work and how such planning and organizing relate to work outcomes, longitudinal study of the management and execution of the Space Lab Mission Development Test 3 (SMD 3) was performed at NASA Ames Research Center. A view of the problems likely to arise in organizations and some methods of coping with these problems are presented as well as the conclusions and recommendations that pertain strictly to SMD 3 management. Emphasis is placed on the broader context of future space facility projects and additional problems that may be anticipated. A model of management that may be used to facilitate problem solving and communication - management by objectives (MBO) is presented. Some problems of communication and emotion management that MBO does not address directly are considered. Models for promoting mature, constructive and satisfying emotional relationships among group members are discussed.

  11. Comparing Visual and Statistical Analysis of Multiple Baseline Design Graphs.

    Science.gov (United States)

    Wolfe, Katie; Dickenson, Tammiee S; Miller, Bridget; McGrath, Kathleen V

    2018-04-01

    A growing number of statistical analyses are being developed for single-case research. One important factor in evaluating these methods is the extent to which each corresponds to visual analysis. Few studies have compared statistical and visual analysis, and information about more recently developed statistics is scarce. Therefore, our purpose was to evaluate the agreement between visual analysis and four statistical analyses: improvement rate difference (IRD); Tau-U; Hedges, Pustejovsky, Shadish (HPS) effect size; and between-case standardized mean difference (BC-SMD). Results indicate that IRD and BC-SMD had the strongest overall agreement with visual analysis. Although Tau-U had strong agreement with visual analysis on raw values, it had poorer agreement when those values were dichotomized to represent the presence or absence of a functional relation. Overall, visual analysis appeared to be more conservative than statistical analysis, but further research is needed to evaluate the nature of these disagreements.

  12. NASA Science4Girls: Engaging Girls in STEM at Their Local Library

    Science.gov (United States)

    Meinke, B.; Smith, D.; Bleacher, L.; Hauck, K.; Soeffing, C.; NASA SMD EPO Community

    2014-07-01

    The NASA Science Mission Directorate (SMD) Science Education and Public Outreach Forums coordinate the participation of SMD education and public outreach (EPO) programs in Women's History Month through the NASA Science4Girls and Their Families initiative. The initiative partners NASA science education programs with public libraries to provide NASA-themed hands-on education activities for girls and their families. The initiative has expanded from the successful 2012 Astro4Girls pilot to engage girls in all four NASA science discipline areas, which broadens the impact of the pilot by enabling audiences to experience the full range of NASA science topics and the different career skills each requires. The events focus on engaging underserved and underrepresented audiences in Science, Technology, Engineering, and Mathematics (STEM) via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences.

  13. What We Need: The 2012 NASA EPO Forum Survey on Two-Year College STEM Teaching

    Science.gov (United States)

    Low, R.; CoBabe-Ammann, E.; Schultz, G.

    2014-07-01

    A survey of community college STEM faculty, administered by the NASA SMD Higher Education Working Group (HEWG), was administered in fall 2012 in an effort to document the demographic make-up and views of community college faculty who teach NASA science-related STEM courses in astronomy, physics, Earth science, and engineering. Nearly half of respondents reported that less than 10% of students in their classroom are “STEMward bound” and indicated the need for STEM resources that can relate science course content and be relevant to the daily life of their students. A number of respondents also noted a new or renewed emphasis on outreach activities within the community served by their institution as part of their job description. The survey suggests specific directions and ways that the NASA SMD EPO forum can support two-year college stakeholders.

  14. Circulating asymmetric dimethylarginine and the risk of preeclampsia: a meta-analysis based on 1338 participants.

    Science.gov (United States)

    Yuan, Jing; Wang, Xinguo; Xie, Yudou; Wang, Yuzhi; Dong, Lei; Li, Hong; Zhu, Tongyu

    2017-07-04

    Patients with preeclampsia have higher circulating asymmetric dimethylarginine (ADMA). However, whether circulating ADMA is elevated before the diagnosis of preeclampsia has not been determined. A meta-analysis of observational studies that reported circulating ADMA level before the onset of preeclampsia was performed. Pubmed and Embase were searched. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the differences in circulating ADMA. A random effect model or a fixed effect model was applied depending on the heterogeneity. The predictive efficacy of circulating ADMA for the incidence of preeclampsia was also explored. Eleven comparisons with 1338 pregnant women were included. The pooled results showed that the circulating ADMA was significantly higher in women who subsequently developed preeclampsia as compared with those did not (SMD: 0.71, p preeclampsia, and retrieved moderate predictive efficacy. Circulating ADMA is elevated before the development of preeclampsia. Studies are needed to evaluate the predictive efficacy of ADMA for the incidence of preeclampsia.

  15. Effectiveness of massage therapy for shoulder pain: a systematic review and meta-analysis.

    Science.gov (United States)

    Yeun, Young-Ran

    2017-05-01

    [Purpose] This study performed an effect-size analysis of massage therapy for shoulder pain. [Subjects and Methods] The database search was conducted using PubMed, CINAHL, Embase, PsycINFO, RISS, NDSL, NANET, DBpia, and KoreaMed. The meta-analysis was based on 15 studies, covering a total of 635 participants, and used a random effects model. [Results] The effect size estimate showed that massage therapy had a significant effect on reducing shoulder pain for short-term efficacy (SMD: -1.08, 95% CI: -1.51 to -0.65) and for long-term efficacy (SMD: -0.47, 95% CI: -0.71 to -0.23). [Conclusion] The findings from this review suggest that massage therapy is effective at improving shoulder pain. However, further research is needed, especially a randomized controlled trial design or a large sample size, to provide evidence-based recommendations.

  16. Effectiveness of massage therapy on the range of motion of the shoulder: a systematic review and meta-analysis.

    Science.gov (United States)

    Yeun, Young-Ran

    2017-02-01

    [Purpose] This study was conducted to identify and analyze the degree of effect of massage therapy on the range of motion of the shoulder. [Subjects and Methods] The database search was conducted using PubMed, CINAHL, Embase, PsycINFO, RISS, NDSL, NANET, DBpia, and KoreaMed. The meta-analysis was based on 7 studies, covered a total of 237 participants, and used a random-effects model. [Results] The effect size estimate showed that massage therapy significantly improved the shoulder range of motion, especially the flexion (SMD: 18.21, 95% CI 1.57-34.85) and abduction (SMD: 22.07, 95% CI 5.84-38.30). [Conclusion] The review findings suggest that massage therapy is effective in improving the shoulder flexion and abduction.

  17. The spray characteristic of gas-liquid coaxial swirl injector by experiment

    Directory of Open Access Journals (Sweden)

    Chen Chen

    2017-01-01

    Full Text Available Using the laser phase Doppler particle analyzer (PDPA, the spray characteristics of gas-liquid coaxial swirl injector were studied. The Sauter mean diameter (SMD, axial velocity and size data rate were measured under different gas injecting pressure drop and liquid injecting pressure drop. Comparing to a single liquid injection, SMD with gas presence is obviously improved. So the gas presence has a significant effect on the atomization of the swirl injector. What’s more, the atomization effect of gas-liquid is enhanced with the increasing of the gas pressure drop. Under the constant gas pressure drop, the injector has an optimal liquid pressure drop under which the atomization performance is best.

  18. Experimental investigation on the effect of injection conditions on spray and atomization of a centrifugal nozzle

    Science.gov (United States)

    Fan, Wei; Song, Haoyi; Fan, Zhencen; Zhao, Lin

    2013-05-01

    The effects of injection parameters on atomization of aviation kerosene (RP-3) were studied using a laser diffraction particle size analyzing system. The test results indicated that Sauter mean diameter (SMD) decreased with the increase of injection temperature. There was a critical temperature for flash evaporation, at which SMD had a sharp decrease. The critical temperature fell at first and then rose with the increase of injection pressure; however, the diameter of a centrifugal nozzle had little influence on the critical temperature. Sauter mean diameter didn't follow the conventional law after flash evaporation. A simple and empirical correlation between critical temperature for flash evaporation and injection parameters was developed from the experimental data, which can be used to evaluate critical temperature for flash evaporation.

  19. Using Authentic Science in the Classroom: NASA's Coordinated Efforts to Enhance STEM Education

    Science.gov (United States)

    Lawton, B.; Schwerin, T.; Low, R.

    2015-11-01

    A key NASA education goal is to attract and retain students in science, technology engineering, and mathematics (STEM) disciplines. When teachers engage students in the examination of authentic data derived from NASA satellite missions, they simultaneously build 21st century technology skills as well as core content knowledge about the Earth and space. In this session, we highlight coordinated efforts by NASA Science Mission Directorate (SMD) Education and Public Outreach (EPO) programs to enhance educator accessibility to data resources, distribute state-of -the-art data tools and expand pathways for educators to find and use data resources. The group discussion explores how NASA SMD EPO efforts can further improve teacher access to authentic NASA data, identifies the types of tools and lessons most requested by the community, and explores how communication and collaboration between product developers and classroom educators using data tools and products can be enhanced.

  20. Properties of DRGs, LBGs, and BzK Galaxies in the GOODS South Field

    Science.gov (United States)

    Grazian, A.; Salimbeni, S.; Pentericci, L.; Fontana, A.; Santini, P.; Giallongo, E.; de Santis, C.; Gallozzi, S.; Nonino, M.; Cristiani, S.; Vanzella, E.

    2007-12-01

    We use the GOODS-MUSIC catalog with multi-wavelength coverage extending from the U band to the Spitzer 8 μm band, and spectroscopic or accurate photometric redshifts to select samples of BM/BX/LBGs, DRGs, and BzK galaxies. We discuss the overlap and the limitations of these selection criteria, which can be overcome with a criterion based on physical parameters (age and star formation timescale). We show that the BzK-PE criterion is not optimal for selecting early type galaxies at the faint end. We also find that LBGs and DRGs contribute almost equally to the global Stellar Mass Density (SMD) at z≥ 2 and in general that star forming galaxies form a substantial fraction of the universal SMD.

  1. Experimental investigation on the spray characteristics of power-law fluid in a swirl injector

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Fuqiang; Chen, Shixing; Guo, Jinpeng; Jiao, Kui; Du, Qing [State Key Laboratory of Engines, Tianjin University, Tianjin, 300072 (China); Chang, Qing, E-mail: duqing@tju.edu.cn [Wuxi Fuel Injection Equipment Research Institute, China FAW CO., Wuxi, 214063 (China)

    2017-06-15

    High-speed photography and 3D phase Doppler methods are used to obtain the swirl jet images, 3D velocities and size distribution of different droplets (including deionized water and two kinds of power-law fluid). For the power-law fluids, a short circular jet is formed after the nozzle exit at low pressure. Along the X direction, the distributions of axial velocity w and Sauter mean diameter (SMD) are symmetrical and increase from the center to both sides. The effect of injection pressure on the radial velocity u is not obvious. Along the Z axis, the absolute value of 3D velocities decreases to some extent with droplets moving downstream. The SMD decreases apparently with the increment of the distance along the Z axis at 1.0 MPa. (paper)

  2. Associations between suicidal behavior and childhood abuse and neglect: A meta-analysis.

    Science.gov (United States)

    Liu, Jianbo; Fang, Yumin; Gong, Jingbo; Cui, Xilong; Meng, Tiantian; Xiao, Bo; He, Yuqiong; Shen, Yanmei; Luo, Xuerong

    2017-10-01

    Relationships of some types of childhood maltreatment and suicidal behavior remain controversial and inconclusive. Medline, Embase, PsycINFO and Cochrane library were searched for eligible studies, and the results were synthesized in meta-analyses. childhood maltreatment was associated positively with suicidal behavior in the total population and maltreatment subgroups. Emotional abuse had the strongest effect (OR =2.33, SMD =0.660, Psuicidal behavior in men and women (women: OR =4.84, Psuicidal behavior in the general population (OR =3.78, Psuicide attempt (OR =1.11, SMD =0.48, Psuicidal ideation. Some subgroup samples were not sufficiently large. Childhood maltreatment increases the risk of suicidal behavior. Emotional abuse had the strongest effect among the five types of maltreatment. The risk of suicidal behavior is higher in the general population, women, and individuals with chronic schizophrenia who have histories of childhood maltreatment. Copyright © 2017. Published by Elsevier B.V.

  3. NASA Science4Girls and Their Families: Connecting Local Libraries with NASA Scientists and Education Programs to Engage Girls in STEM

    Science.gov (United States)

    Bleacher, L. V.; Meinke, B.; Hauck, K.; Soeffing, C.; Spitz, A.

    2014-01-01

    NASA Science4Girls and Their Families (NS4G) partners NASA Science Mission Directorate (SMD) education programs with public libraries to provide hands-on science, technology, engineering, and math (STEM) activities and career information for girls and their families, along with training for librarians, in conjunction with Women's History Month (March). NS4G is a collaboration among education teams within the four NASA SMD education and public outreach (E/PO) Forums: Planetary, Earth, Astrophysics, and Heliophysics. It began in 2012 as an Astrophysics-led program (Astro4Girls) with 9 events around the country. Upon expanding among the four Forums, over 73 events were held in Spring 2013 (Fig. 1), with preparations underway for events in Spring 2014. All events are individually evaluated by both the student participants and participating librarians to assess their effectiveness in addressing audience needs.

  4. Submerged membrane distillation for seawater desalination

    KAUST Repository

    Francis, Lijo; Ghaffour, NorEddine; Alsaadi, Ahmad Salem; Amy, Gary L.

    2014-01-01

    A submerged membrane distillation (SMD) process for fresh water production from Red Sea water using commercially available hollow fiber membranes has been successfully employed and compared with the conventional direct contact membrane distillation (DCMD) process. The hollow fiber membranes have been characterized for its morphology using field effect scanning electron microscope. In SMD process, a bunch of hollow fiber membranes are glued together at both ends to get a simplified open membrane module assembly submerged into the coolant tank equipped with a mechanical stirrer. Hot feed stream is allowed to pass through the lumen side of the membrane using a feed pump. Continuous stirring at the coolant side will reduce the temperature and concentration polarization. During the conventional DCMD process, using feed-coolant streams with co-current and counter-current flows has been tested and the results are compared in this study. In SMD process, a water vapor flux of 10.2 kg m-2 h-1 is achieved when using a feed inlet temperature of 80°C and coolant temperature of 20°C. Under the same conditions, during conventional DCMD process, a water vapor flux of 11.6 and 10.1 kg m-2 h-1 were observed during counter-current and co-current flow streams, respectively. Results show that the water production in the SMD process is comparable with the conventional DCMD process, while the feed-coolant flow streams are in the co-current direction. During conventional DCMD operation, a 15% increase in the water production is observed when feed-coolant streams are in the counter-current direction compared to the co-current direction. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  5. Effect of dipeptidyl peptidase-4 inhibitors on circulating tumor necrosis factor-α concentrations: A systematic review and meta-analysis of controlled trials.

    Science.gov (United States)

    Atkin, Stephen L; Katsiki, Niki; Banach, Maciej; Mikhailidis, Dimitri P; Pirro, Matteo; Sahebkar, Amirhossein

    2017-09-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus. There are also reports of an effect of these drugs in reducing inflammation through inhibition of tumor necrosis factor-α (TNF-α) that is an important mediator for several inflammatory processes. The present systematic review and meta-analysis were performed to evaluate the effect of DPP-4 inhibitors on circulating TNF-α levels in T2DM patients. A systematic review and a meta-analysis were undertaken on all controlled trials of DPP-4 inhibitors that included measurement of TNF-α. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. Eight eligible articles (6 with sitagliptin and 2 with vildagliptin) comprising 9 treatment arms were selected for this meta-analysis. Meta-analysis suggested a significant reduction of circulating TNF-α concentrations following treatment with DPP-4 inhibitors (SMD: -1.84, 95% CI: -2.88, -0.80, p=0.001). The effect size was robust in the sensitivity analysis and not mainly driven by a single study. A subgroup analysis did not suggest any significant difference between the TNF-α-lowering activity of sitagliptin (SMD: -1.49, 95% CI: -2.89, -0.10) and vildagliptin (SMD: -2.80, 95% CI: -4.98, -0.61) (p=0.326). This meta-analysis of the 8 available controlled trials showed that DPP-4 inhibition in patients with type 2 diabetes mellitus was associated with significant reductions in plasma TNF-α levels with no apparent difference between sitagliptin and vildagliptin. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The effect of footwear on running performance and running economy in distance runners.

    Science.gov (United States)

    Fuller, Joel T; Bellenger, Clint R; Thewlis, Dominic; Tsiros, Margarita D; Buckley, Jonathan D

    2015-03-01

    The effect of footwear on running economy has been investigated in numerous studies. However, no systematic review and meta-analysis has synthesised the available literature and the effect of footwear on running performance is not known. The aim of this systematic review and meta-analysis was to investigate the effect of footwear on running performance and running economy in distance runners, by reviewing controlled trials that compare different footwear conditions or compare footwear with barefoot. The Web of Science, Scopus, MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), EMBASE, AMED (Allied and Complementary Medicine), CINAHL and SPORTDiscus databases were searched from inception up until April 2014. Included articles reported on controlled trials that examined the effects of footwear or footwear characteristics (including shoe mass, cushioning, motion control, longitudinal bending stiffness, midsole viscoelasticity, drop height and comfort) on running performance or running economy and were published in a peer-reviewed journal. Of the 1,044 records retrieved, 19 studies were included in the systematic review and 14 studies were included in the meta-analysis. No studies were identified that reported effects on running performance. Individual studies reported significant, but trivial, beneficial effects on running economy for comfortable and stiff-soled shoes [standardised mean difference (SMD) beneficial effect on running economy for cushioned shoes (SMD = 0.37; P beneficial effect on running economy for training in minimalist shoes (SMD = 0.79; P beneficial effects on running economy for light shoes and barefoot compared with heavy shoes (SMD running was identified (P running economy. Certain models of footwear and footwear characteristics can improve running economy. Future research in footwear performance should include measures of running performance.

  7. Transmission policy in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Joskow, P.L. [Massachusetts Institute of Technology, Cambridge, MA (United States). Department of Economics

    2005-06-01

    This paper provides an overview of the development of electric power transmission access, pricing and investment policies in the US over the last 15 years and evaluates the current state of those policies. Pre-liberalization transmission access and pricing policies are reviewed first since more recent policies have evolved from them. FERC's efforts to ensure that transmission owning utilities provide non-discriminatory access and pricing to wholesale transmission customers, culminating in Order 888 and 889 are discussed. These rules did not respond to problems created by a highly balkanized transmission system and only partially responded to problems caused by common ownership and operation of transmission networks with generating and marketing businesses in the same regions. These problems motivated FERC to seek to create Regional Transmission Organizations (RTO) meeting a long list of criteria related to governance, network operations, transmission pricing and investment as reflected in Order 2000. The slow pace of 'voluntary' reform following Order 2000 led FERC to issue a proposed Standard Market Design Rule (SMD) which provided more detailed prescriptions for wholesale market design, network operations, regional planning, resource adequacy, and transmission investment. The SMD rule confronted enormous resistance from groups of utilities and states that had not embraced an electricity sector liberalization agenda. However, many of the provisions of the SMD are being implemented by the RTOs and ISOs in the Northeast and Midwest. PJM's market rules and transmission pricing, planning and investment policies are reviewed as an articulation of FERC's RTO and SMD visions. (author)

  8. [Acupuncture Therapy versus Disease-modifying Antirheumatic Drugs for the Treatment of Ankylosing Spondylitis--a Meta-analysis].

    Science.gov (United States)

    Lv, Zheng-tao; Zhou, Xiang; Chen, An-min

    2015-01-01

    We conducted a meta-analysis evaluating the efficacy and safety of acupuncture compared to disease-modifying antirheumatic drugs in patients with ankylosing spondylitis. Four databases including Pubmed, EMBASE, Cochrane library, and ISI Web of Science were searched in December 2014, taking also the reference section into account. Randomized controlled trials that aimed to assess the efficacy of acupuncture therapy were identified. The inclusion criteria for the outcome measurements were the clinical effect, ESR, occipital wall test, chest expansion, CRP and finger ground distance. Finally, six studies met these inclusion criteria. Two reviewers screened each article independently and were blinded to the findings of each other. We analyzed data from 6 RCTs involving 541 participants. Acupuncture therapy could further improve the clinical effect (OR = 3.01; 95% CI, 1.48-6.13; P = 0.002) and reduce ESR level (SMD = -0.77; 95% CI, -1.46 to -0.08; P = 0.03) compared to DMARDs; a combination of acupuncture and DMARDs could further improve clinical effect (OR = 3.20, 95% CI, 1.36-7.54; P = 0.008), occipital-wall distance (SMD = -0.84; 95% CI, -1.37 to -0.31; P = 0.002), chest expansion (SMD = 0.38; 95% CI, 0.16-0.60; P = 0.0009), and finger-ground distance (SMD = -0.48; 95% CI, -0.87 to -0.09; P = 0.02) as compared to DMARDs treatment alone. Our findings support that acupuncture therapy could be an option to relieve symptoms associated with AS. These results should be interpreted cautiously due to the generally poor methodological qualities of the included trials. © 2015 S. Karger GmbH, Freiburg.

  9. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Vittorio Unfer1,

    2017-10-01

    Full Text Available Myo-inositol (MI supplementation in women with polycystic ovary syndrome (PCOS has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016. Only randomized controlled trials (RCTs investigating the effects of MI alone or combined with DdCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = −1.021 μU/mL, 95% CI: −1.791 to −0.251, P = 0.009 and homeostasis model assessment (HOMA index (SMD = −0.585, 95% CI: −1.145 to −0.025, P = 0.041 were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = −0.49, 95% CI: −1.072 to 0.092, P = 0.099, whereas androstenedione levels remained unaffected. Throughout a subgroup’s meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050–0.801, P = 0.026. These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

  10. Cognitive, motor, behavioural and academic performances of children born preterm: a meta-analysis and systematic review involving 64 061 children.

    Science.gov (United States)

    Allotey, J; Zamora, J; Cheong-See, F; Kalidindi, M; Arroyo-Manzano, D; Asztalos, E; van der Post, Jam; Mol, B W; Moore, D; Birtles, D; Khan, K S; Thangaratinam, S

    2018-01-01

    Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy. To quantify the long-term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term-born children. PubMed and Embase were searched from January 1980 to December 2016 without language restrictions. Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term-born cohort. We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model. We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67; 95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38-48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed according to the severity of prematurity (I 2 = 49.4%, P = 0.03). Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children. Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood. © 2017 Royal College of Obstetricians and Gynaecologists.

  11. Are interventions for low-income groups effective in changing healthy eating, physical activity and smoking behaviours? A systematic review and meta-analysis.

    Science.gov (United States)

    Bull, Eleanor R; Dombrowski, Stephan U; McCleary, Nicola; Johnston, Marie

    2014-11-28

    To conduct a systematic review and meta-analysis examining the effectiveness of behavioural interventions targeting diet, physical activity or smoking in low-income adults. Systematic review with random effects meta-analyses. Studies before 2006 were identified from a previously published systematic review (searching 1995-2006) with similar but broader inclusion criteria (including non-randomised controlled trials (RCTs)). Studies from 2006 to 2014 were identified from eight electronic databases using a similar search strategy. MEDLINE, EMBASE, PsycINFO, ASSIA, CINAHL, Cochrane Controlled Trials, Cochrane Systematic Review and DARE. RCTs and cluster RCTs published from 1995 to 2014; interventions targeting dietary, physical activity and smoking; low-income adults; reporting of behavioural outcomes. Dietary, physical activity and smoking cessation behaviours. 35 studies containing 45 interventions with 17,000 participants met inclusion criteria. At postintervention, effects were positive but small for diet (standardised mean difference (SMD) 0.22, 95% CI 0.14 to 0.29), physical activity (SMD 0.21, 95% CI 0.06 to 0.36) and smoking (relative risk (RR) of 1.59, 95% CI 1.34 to 1.89). Studies reporting follow-up results suggested that effects were maintained over time for diet (SMD 0.16, 95% CI 0.08 to 0.25) but not physical activity (SMD 0.17, 95% CI -0.02 to 0.37) or smoking (RR 1.11, 95% CI 0.93 to 1.34). Behaviour change interventions for low-income groups had small positive effects on healthy eating, physical activity and smoking. Further work is needed to improve the effectiveness of behaviour change interventions for deprived populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Two opposite hysteresis curves in semiconductors with mobile dopants

    OpenAIRE

    Lee, Jae Sung; Lee, Shin Buhm; Kahng, Byungnam; Noh, Tae Won

    2012-01-01

    Recent experimental researches on semiconductors with mobile dopants (SMD) have reported unconventional hysteretic current-voltage (I-V) curves, which form dynamically in either one of the two opposite directions, the counter-figure-eight and figure-eight ways. However the fundamental theory for the formation of the two directions is still absent, and this poses a major barrier for researches oriented to applications. Here, we introduce a theoretical model to explain the origin of the two dir...

  13. Neuromuscular training in construction workers: a longitudinal controlled pilot study.

    Science.gov (United States)

    Faude, Oliver; Donath, Lars; Bopp, Micha; Hofmann, Sara; Erlacher, Daniel; Zahner, Lukas

    2015-08-01

    Many accidents at construction sites are due to falls. An exercise-based workplace intervention may improve intrinsic fall risk factors. In this pilot study, we aimed at evaluating the effects of neuromuscular exercise on static and functional balance performance as well as on lower limb explosive power in construction workers. Healthy middle-aged construction workers were non-randomly assigned to an intervention [N = 20, age = 40.3 (SD 8.3) years] or a control group [N = 20, age = 41.8 (9.9) years]. The intervention group performed static and dynamic balance and strength exercises (13 weeks, 15 min each day). Before and after the intervention and after an 8-week follow-up, unilateral postural sway, backward balancing (on 3- and 4.5-cm-wide beams) as well as vertical jump height were assessed. We observed a group × time interaction for postural sway (p = 0.002) with a reduction in the intervention group and no relevant change in the control group. Similarly, the number of successful steps while walking backwards on the 3-cm beam increased only in the intervention group (p = 0.047). These effects were likely to most likely practically beneficial from pretest to posttest and to follow-up test for postural sway (+12%, standardized mean difference (SMD) = 0.65 and 17%, SMD = 0.92) and backward balancing on the 3-cm beam (+58%, SMD = 0.59 and 37%, SMD = 0.40). Fifteen minutes of neuromuscular training each day can improve balance performance in construction workers and, thus, may contribute to a decreased fall risk.

  14. A systematic review of maggot debridement therapy for chronically infected wounds and ulcers.

    Science.gov (United States)

    Sun, Xinjuan; Jiang, Kechun; Chen, Jingan; Wu, Liang; Lu, Hui; Wang, Aiping; Wang, Jianming

    2014-08-01

    This study aimed to systematically evaluate maggot debridement therapy (MDT) in the treatment of chronically infected wounds and ulcers. We performed a meta-analysis referring to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We searched for published articles in the following databases: PubMed, Web of Science, Embase, Wanfang (Chinese), and the China National Knowledge Infrastructure (CNKI). The latest search was updated on March 14, 2014. For dichotomous outcomes, the effects of MDT were expressed as the relative risk (RR) and 95% confidence interval (CI). For continuous outcomes with different measurement scales, we calculated the standardized mean difference (SMD). The pooled effects were estimated using a fixed effect model or random effect model based on the heterogeneity test. Subgroup analyses were performed according to the types of wounds or ulcers. MDT had a significantly increased positive effect on wound healing compared with conventional therapies, with a pooled RR of 1.80 (95% CI 1.24-2.60). The subgroup analysis revealed that the combined RRs were 1.79 (95% CI 0.95-3.38) for patients with diabetic foot ulcers (DFU) and 1.70 (95% CI 1.28-2.27) for patients with other types of ulcers. The time to healing of the ulcers was significantly shorter among patients treated with MDT, with a pooled SMD of -0.95 (95% CI -1.24, -0.65). For patients with DFU, the SMD was -0.79 (95% CI -1.18, -0.41), and for patients with other types of ulcers, the SMD was -1.16 (95% CI -1.63, -0.69). MDT not only shortened the healing time but also improved the healing rate of chronic ulcers. Therefore, MDT may be a feasible alternative in the treatment of chronic ulcers. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Antioxidant therapy for pain relief in patients with chronic pancreatitis: systematic review and meta-analysis.

    Science.gov (United States)

    Cai, Guo-Hong; Huang, Jing; Zhao, Yan; Chen, Jing; Wu, Huang-Hui; Dong, Yu-Lin; Smith, Howard S; Li, Yun-Qing; Wang, Wen; Wu, Sheng-Xi

    2013-01-01

    Currently, there is no specific therapy for chronic pancreatitis (CP). The treatment of micronutrient antioxidant therapy for painful CP has been sporadically used for more than 30 years, however, its efficacy are still poorly understood. The purpose of this meta-analysis is to investigate the safety and efficacy of antioxidant therapy for pain relief in patients with CP. University Hospital in China Systematic review and meta-analysis Two authors independently reviewed the search results and extracted data and disagreements were resolved by discussion. Effects were summarized using standardized mean differences (SMDs), weighted mean differences, or odds ratio (OR) according to the suitable effect model. MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials  were searched from 1980 through December 2012. Randomized controlled trials (RCTs) that studied antioxidant supplementation for pain relief in patients with CP were analyzed. Nine randomized controlled trials (RCTs) involving 390 patients were included. Overall, there was no association of antioxidant therapy with pain reduction in CP patients (SMD, -0.55; 95% CI, -1.22 to 0.12; P = 0.67). However, antioxidant therapy significantly increased blood levels of antioxidants in CP patients versus the placebo group (SMD, 1.08; 95% CI, 0.74 to 1.43; P pain relief (SMD, -0.93; 95% CI, -1.72 to -0.14; P = 0.02), while the trials in which a single antioxidant was used revealed no significant pain relief (SMD, -0.12; 95% CI, -1.23 to 0.99; P = 0.83) in CP patients. Strong evidence was obtained that the antioxidants increased adverse effects (OR, 6.09; 95% CI, 2.29 to 16.17, P pain relief in CP patients. Measures of total antioxidant status may not help to monitor the efficacy of antioxidant therapy for patients with CP.

  16. Spatiotemporal, kinematic, force and muscle activation outcomes during gait and functional exercise in water compared to on land: A systematic review.

    Science.gov (United States)

    Heywood, Sophie; McClelland, Jodie; Geigle, Paula; Rahmann, Ann; Clark, Ross

    2016-07-01

    Exercises replicating functional activities are commonly used in aquatic rehabilitation although it is not clear how the movement characteristics differ between the two environments. A systematic review was completed in order to compare the biomechanics of gait, closed kinetic chain and plyometric exercise when performed in water and on land. Databases including MEDLINE, CINAHL, SPORTDiscus, Embase and the Cochrane library were searched. Studies were included where a functional lower limb activity was performed in water and on land with the same instructions. Standardized mean differences (SMD) and 95% confidence intervals were calculated for spatiotemporal, kinematic, force and muscle activation outcomes. 28 studies included walking or running (19 studies), stationary running (three), closed kinetic chain exercise (two), plyometric exercise (three) and timed-up and go (one). Very large effect sizes showed self-selected speed of walking (SMD >4.66) and vertical ground reaction forces (VGRF) (SMD >1.91) in water were less than on land, however, lower limb range of movement and muscle activity were similar. VGRF in plyometric exercise was lower in water when landing but more similar between the two environments in propulsion. Maximal speed of movement for walking and stationary running was lower in water compared to on land (SMD>3.05), however was similar in propulsion in plyometric exercise. Drag forces may contribute to lower self-selected speed of walking. Monitoring speed of movement in water assists in determining the potential advantages or limitations of aquatic exercise and the task specificity to land-based function. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Gaming for Health: Systematic Review and Meta-analysis of the Physical and Cognitive Effects of Active Computer Gaming in Older Adults.

    Science.gov (United States)

    Howes, Sarah C; Charles, Darryl K; Marley, Joanne; Pedlow, Katy; McDonough, Suzanne M

    2017-12-01

    Active computer gaming (ACG) is a method of facilitating physical activity in older people to improve health outcomes. The purpose of this study was to update and extend a systematic review of the evidence for ACG to determine its effects on physical and cognitive health in older adults. MEDLINE, EMBASE, CENTRAL in the Cochrane Library, and PsycINFO databases were searched from the date of the previous review (2011) to May 2016. Eligible articles were randomized controlled trials (RCTs) investigating the effect of ACG in adults aged 65 and older. Thirty-five studies were eligible for inclusion. Two review authors independently conducted data extraction, risk-of-bias assessment, and coding of behavior change techniques. Outcomes of interest were analyzed as continuous data and pooled as standardized mean differences (SMD) and 95% confidence intervals (CI). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to determine the quality of the evidence. Behavior change techniques (N = 106) were coded in the included studies (mean = 3.02). Data were pooled for 5 main outcomes of interest. Significant moderate effects in favor of ACG were observed for balance (SMD = 0.52, 95% CI = 0.24 to 0.79; 17 studies; 743 participants), for functional exercise capacity when intervention delivery was >120 minutes per week (SMD = 0.53, 95% CI = 0.15 to 0.90; 5 studies; 116 participants), and for cognitive function (SMD = -0.48, 95% CI = -0.80 to 0.17; 8 studies; 459 participants). There was no significant effect observed for functional mobility or fear of falling. The quality of the evidence for all comparisons was graded low or very low. At present there is very little confidence that ACG improves physical and cognitive outcomes in older adults. © 2017 American Physical Therapy Association

  18. A Meta-Analysis of Randomized Controlled Trials of Yiqi Yangyin Huoxue Method in Treating Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Jiao Ying Ou

    2016-01-01

    Full Text Available Objective. The purpose of this systematic review is to evaluate the evidence of Yiqi Yangyin Huoxue Method for diabetic nephropathy. Methods. 11 electronic databases, through September 2015, were searched to identify randomized controlled trials of Yiqi Yangyin Huoxue Method for diabetic nephropathy. The quality of the included trials was assessed using the Jadad scale. Results. 26 randomized controlled trials were included in our review. Of all the included trials, most of them were considered as high quality. The aggregated results suggested that Yiqi Yangyin Huoxue Method is beneficial to diabetic nephropathy in bringing down the microalbuminuria (SMD = −0.98, 95% CI −1.22 to −0.74, serum creatinine (SMD = −0.56, 95% CI −0.93 to −0.20, beta-2 microglobulin (MD = 0.06, 95% CI 0.01 to 0.12, fasting plasma glucose (MD = −0.35, 95% CI −0.62 to −0.08, and 2-hour postprandial blood glucose (MD = 1.13, 95% CI 0.07 to 2.20, but not in decreasing blood urea nitrogen (SMD = −0.72, 95% CI −1.47 to 0.02 or 2-hour postprandial blood glucose (SMD = −0.48, 95% CI −1.01 to 0.04. Conclusions. Yiqi Yangyin Huoxue Method should be a valid complementary and alternative therapy in the management of diabetic nephropathy, especially in improving UAER, serum creatinine, fasting blood glucose, and beta-2 microglobulin. However, more studies with long follow-up are warrant to confirm the current findings.

  19. Circulating Betatrophin Levels and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Fei-Juan Kong

    Full Text Available The association between circulating betatrophin levels and gestational diabetes mellitus (GDM is controversial. The aim of our study was to systematically review available literature linking betatrophin to GDM for a comprehensive understanding of the relationship between circulating betatrophin levels and GDM in human.PubMed, The Cochrane Library, Medline and CNKI were searched for studies published up to August 2016. Manual searches of references of the relevant original studies were conducted. Pooled estimates were measured using the fixed or random effect model. Overall effect was reported in a standard mean difference (SMD. All data were analyzed with Review Manager 5.3 and Stata 12.0.Of 25 references reviewed, 8 studies met our inclusion criteria and contributed to meta-analysis. All the studies were used to evaluate the relationship between betatrophin levels in blood and GDM. Betatrophin levels were significantly elevated in women with GDM compared with those without GDM (SMD = 1.05; 95% CI: 0.41-1.68, P = 0.001. This evidence was more consistent among women with betatrophin blood draw during the third trimester (SMD = 1.3, 95% CI: 1-1.61, P < 0.001 and for women BMI ≥ 28 kg/m2 (SMD = 1.53, 95% CI: 1.30-1.75, P < 0.001.The evidences from this meta-analysis indicated that the levels of circulating betatrophin were significantly elevated among women with GDM compared with women with normal glucose tolerance, especially with BMI ≥ 28 kg/m2 and in the third trimester.

  20. Tools for Engaging Scientists in Education and Public Outreach: Resources from NASA's Science Mission Directorate Forums

    Science.gov (United States)

    Buxner, S.; Grier, J.; Meinke, B. K.; Gross, N. A.; Woroner, M.

    2014-12-01

    The NASA Science Education and Public Outreach (E/PO) Forums support the NASA Science Mission Directorate (SMD) and its E/PO community by enhancing the coherency and efficiency of SMD-funded E/PO programs. The Forums foster collaboration and partnerships between scientists with content expertise and educators with pedagogy expertise. We will present tools to engage and resources to support scientists' engagement in E/PO efforts. Scientists can get connected to educators and find support materials and links to resources to support their E/PO work through the online SMD E/PO community workspace (http://smdepo.org) The site includes resources for scientists interested in E/PO including one page guides about "How to Get Involved" and "How to Increase Your Impact," as well as the NASA SMD Scientist Speaker's Bureau to connect scientists to audiences across the country. Additionally, there is a set of online clearinghouses that provide ready-made lessons and activities for use by scientists and educators: NASA Wavelength (http://nasawavelength.org/) and EarthSpace (http://www.lpi.usra.edu/earthspace/). The NASA Forums create and partner with organizations to provide resources specifically for undergraduate science instructors including slide sets for Earth and Space Science classes on the current topics in astronomy and planetary science. The Forums also provide professional development opportunities at professional science conferences each year including AGU, LPSC, AAS, and DPS to support higher education faculty who are teaching undergraduate courses. These offerings include best practices in instruction, resources for teaching planetary science and astronomy topics, and other special topics such as working with diverse students and the use of social media in the classroom. We are continually soliciting ways that we can better support scientists' efforts in effectively engaging in E/PO. Please contact Sanlyn Buxner (buxner@psi.edu) or Jennifer Grier (jgrier@psi.edu) to

  1. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Linying Peng

    Full Text Available BACKGROUND: Postoperative cognitive dysfunction (POCD is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. METHODS: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12.The standardized mean difference (SMD and the 95% confidence interval (95%CI were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. RESULTS: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI] (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies, and interleukin(IL-6 (SMD[95%CI] (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies, but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies. CONCLUSIONS: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

  2. Clinical effect of probiotics in treatment of liver cirrhosis: a Meta-analysis

    Directory of Open Access Journals (Sweden)

    SUN Yuanpei

    2018-01-01

    Full Text Available Objective To investigate the clinical effect of probiotics in the treatment of liver cirrhosis through a systematic review. Methods PubMed, Embase, Cochrane Library, Chinese Scientific Journal Full-Text Database, VIP, and Wanfang Data were searched for randomized controlled trials (RCTs of probiotics for the treatment of liver cirrhosis. RevMan 5.3 software was used for the meta-analysis of the articles screened out. Rate difference (RD and its 95% confidence interval (95% CI were used as effect size indicators for binary variables; weighted mean difference (WMD was used for evaluating continuous variables with the same unit, and standardized mean difference (SMD and its 95% CI were used for evaluating continuous variables with different units. Funnel plots were used to analyze publication bias. Results A total of 15 RCTs which met the inclusion criteria were included, and there were 1411 patients with liver cirrhosis in total (726 in treatment group and 685 in control group. Compared with the control group, the treatment group had significant improvements in overall response rate (RD=0.28, 95%CI:0.22-0.34, P<0.001 and biochemical parameters for liver function including alanine aminotransferase (SMD=-0.90, 95%CI:-1.14 to -0.66, P<0.001, total bilirubin (WMD=-15.99, 95%CI:-26.42 to -5.57, P<0.001, albumin (SMD=0.66, 95%CI:0.40-0.93, P<0.001, endotoxin (SMD=-1.13, 95%CI:-2.11 to -0.15, P<0001, and blood ammonia (WMD=-15.86, 95%CI:-21.54 to -10.18, P<0.001. Conclusion Probiotics can significantly improve liver function in patients with liver cirrhosis, effectively inhibit the progression of liver cirrhosis, reduce the risk of complications including hepatic encephalopathy, and increase overall response rate and have good tolerability.

  3. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Binh Khanh [Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City (Viet Nam); Li, Mai Suan, E-mail: masli@ifpan.edu.pl [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland)

    2011-07-08

    Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  4. Efficacy and safety of Modified Tongxie Yaofang in diarrhea-predominant irritable bowel syndrome management: A meta-analysis of randomized, positive medicine-controlled trials.

    Directory of Open Access Journals (Sweden)

    Yun-Kai Dai

    Full Text Available To systematically evaluate the efficacy and safety of Modified Tongxie Yaofang (M-TXYF for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D.Electronic databases including PubMed, Springer Link, EMBASE, China National Knowledge Infrastructure (CNKI, Chinese Biomedical Literature (CBM, Wanfang, and Chinese Scientific Journals Database (VIP were conducted from their inception through May 11, 2017 without language restrictions. Primary and secondary outcomes were estimated by 95% confidence intervals (CI. RevMan 5.3 and the Cochrane Collaboration's risk of bias tool were analyzed for this meta-analysis.Twenty-three literatures with a total of 1972 patients were included for the meta-analysis. The overall risk of bias evaluation was low. The pooled odds ratio showed that M-TXYF was significantly superior to routine pharmacotherapies (RP in clinical therapeutic efficacy (OR 4.04, 95% CI 3.09, 5.27, P < 0.00001, therapeutic gain = 17.6%, number needed to treat (NNT = 5.7. Moreover, compared with RP, M-TXYF showed that it can significantly reduce the scores of abdominal pain (standardized mean difference (SMD -1.27; 95% CI -1.99, -0.56; P = 0.0005, abdominal distention (SMD -0.37; 95% CI -0.73, -0.01; P = 0.09, diarrhea (SMD -1.10; 95% CI -1.95, -0.25; P = 0.01, and frequency of defecation (SMD -1.42; 95% CI -2.19, -0.65; P = 0.0003. The differences of the adverse events between experiment and control groups had no statistical significance.This meta-analysis indicated that M-TXYF could be a promising Chinese herbal formula in treating IBS-D. However, considering the lack of higher quality of randomized controlled trials (RCTs, highly believable evidences should be required.

  5. The value of diffusion tensor imaging in differentiating high-grade gliomas from brain metastases: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rui Jiang

    Full Text Available Differentiation of high-grade gliomas and solitary brain metastases is an important clinical issue because the treatment strategies differ greatly. Our study aimed to investigate the potential value of diffusion tensor imaging (DTI in differentiating high-grade gliomas from brain metastases using a meta-analytic approach.We searched Pubmed, Embase and the Cochrane Library for relevant articles published in English. Studies that both investigated high-grade gliomas and brain metastases using DTI were included. Random effect model was used to compare fractional anisotropy (FA and mean diffusivity (MD values in the two tumor entities.Nine studies were included into the meta-analysis. In the peritumoral region, compared with brain metastases, high-grade gliomas had a significant increase of FA (SMD  = 0.47; 95% CI, 0.22-0.71; P<0.01 and a significant decrease of MD (SMD  = -1.49; 95% CI, -1.91 to -1.06; P<0.01. However, in the intratumoral area, no significant change in FA (SMD  = 0.16; 95% CI, -0.49 to 0.82; P = 0.73 or MD (SMD  = 0.34; 95% CI, -0.91 to 1.60; P = 0.59 was detected between gliomas and metastases.High-grade gliomas may be distinguished from brain metastases by comparing the peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing solitary intracranial lesions.

  6. Comparative efficacy and safety of the left versus right radial approach for percutaneous coronary procedures: a meta-analysis including 6870 patients

    Directory of Open Access Journals (Sweden)

    S.L. Xia

    2015-08-01

    Full Text Available The radial approach is widely used in the treatment of patients with coronary artery disease. We conducted a meta-analysis of published results on the efficacy and safety of the left and right radial approaches in patients undergoing percutaneous coronary procedures. A systematic search of reference databases was conducted, and data from 14 randomized controlled trials involving 6870 participants were analyzed. The left radial approach was associated with significant reductions in fluoroscopy time [standardized mean difference (SMD=-0.14, 95% confidence interval (CI=-0.19 to -0.09; P<0.00001] and contrast volume (SMD=-0.07, 95%CI=-0.12 to -0.02; P=0.009. There were no significant differences in rate of procedural failure of the left and the right radial approaches [risk ratios (RR=0.98; 95%CI=0.77-1.25; P=0.88] or procedural time (SMD=-0.05, 95%CI=0.17-0.06; P=0.38. Tortuosity of the subclavian artery (RR=0.27, 95%CI=0.14-0.50; P<0.0001 was reported more frequently with the right radial approach. A greater number of catheters were used with the left than with the right radial approach (SMD=0.25, 95%CI=0.04-0.46; P=0.02. We conclude that the left radial approach is as safe as the right radial approach, and that the left radial approach should be recommended for use in percutaneous coronary procedures, especially in percutaneous coronary angiograms.

  7. Development of Charge Sensitive Preamplifier and Readout Integrate Circuit Board for High Resolution Detector using ASIC Process

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, J. Y.; Kim, J. H.; Park, J. M.; Yang, J. Y.; Kim, K. Y.; Kim, Y. S. [RadTek Co., Daejeon (Korea, Republic of)

    2010-06-15

    - Design of discrete type charge sensitive amplifier for high resolution semi-conductor sensor - Design and develop the test board for the performance of charge sensitive amplifier with sensor - Performance of electrical test for the sensor and charge sensitive amplifier - Development of prototype 8 x 8 array type detector module - Noise equivalent charge test for the charge sensitive amplifier - Design and development of Micro SMD discrete type amplifier applying ASIC procedure - Development of Hybrid type charge sensitive amplifier including shape

  8. The Effects of Music on Pain: A Meta-Analysis.

    Science.gov (United States)

    Lee, Jin Hyung

    2016-01-01

    Numerous meta-analyses have been conducted on the topic of music and pain, with the latest comprehensive study published in 2006. Since that time, more than 70 randomized controlled trials (RCTs) have been published, necessitating a new and comprehensive review. The aim of this meta-analysis was to examine published RCT studies investigating the effect of music on pain. The present study included RCTs published between 1995 and 2014. Studies were obtained by searching 12 databases and hand-searching related journals and reference lists. Main outcomes were pain intensity, emotional distress from pain, vital signs, and amount of analgesic intake. Study quality was evaluated according to the Cochrane Collaboration guidelines. Analysis of the 97 included studies revealed that music interventions had statistically significant effects in decreasing pain on 0-10 pain scales (MD = -1.13), other pain scales (SMD = -0.39), emotional distress from pain (MD = -10.83), anesthetic use (SMD = -0.56), opioid intake (SMD = -0.24), non-opioid intake (SMD = -0.54), heart rate (MD = -4.25), systolic blood pressure (MD = -3.34), diastolic blood pressure (MD = -1.18), and respiration rate (MD = -1.46). Subgroup and moderator analyses yielded additional clinically informative outcomes. Considering all the possible benefits, music interventions may provide an effective complementary approach for the relief of acute, procedural, and cancer/chronic pain in the medical setting. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Determine spray droplets on water sensitive paper (WSP) for low pressure deflector nozzle using image J

    Science.gov (United States)

    Sies, M. F.; Madzlan, N. F.; Asmuin, N.; Sadikin, A.; Zakaria, H.

    2017-09-01

    In this study, determine of spray droplets size (SMD) using water sensitive paper (WSP) at low fluid pressure with deflector nozzle or tangential flow nozzle model Delavan AL75 and New Design Nozzle with two different type of swirl (ND2.5 A1.0 & ND2.5 B1.0). These three deflected flat sprays have used at different liquid mixing ratio. These liquid mixture ratios are pure water, 10% of lime juice + 90% of water (L10W90) and 30% of lime juice + 70% of water (L30W70). WSP is used to collect the spray droplets from nozzles. The operational liquid pressure of each nozzle is 3 bar, while air operational pressures are 3 bar and 6 bar. Then, the WSP were scanned using scanner then it was analyzed using ImageJ software. ImageJ can be used for determining the diameter of droplets size on the WSP. As the results from an experiment, the AL75 nozzle recorded the lowest Sauter mean diameter which is 193.69μm at 6 bar of pressurized air while ND2.5 A1.0 recorded the highest Sauter mean diameter which is 353.61µm at 3 bar of pressurized air. Summary from the experiment shows that the higher of droplet size is because of the lower air pressure (3 Bar). Then, increasing of liquid viscosity also increase the SMD. The orifice diameter for New Design nozzle (ND-2.5) is smaller than AL75, which are 2.5mm and 2.8mm respectively. The different nozzle design also gives effect the SMD. WSP is an alternative method to determine SMD for spray droplets with the low cost if compared to Phase Doppler Anemometry (PDA).

  10. Effects of Napping During Shift Work on Sleepiness and Performance in Emergency Medical Services Personnel and Similar Shift Workers: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Martin-Gill, Christian; Barger, Laura K; Moore, Charity G; Higgins, J Stephen; Teasley, Ellen M; Weiss, Patricia M; Condle, Joseph P; Flickinger, Katharyn L; Coppler, Patrick J; Sequeira, Denisse J; Divecha, Ayushi A; Matthews, Margaret E; Lang, Eddy S; Patterson, P Daniel

    2018-02-15

    Scheduled napping during work shifts may be an effective way to mitigate fatigue-related risk. This study aimed to critically review and synthesize existing literature on the impact of scheduled naps on fatigue-related outcomes for EMS personnel and similar shift worker groups. A systematic literature review was performed of the impact of a scheduled nap during shift work on EMS personnel or similar shift workers. The primary (critical) outcome of interest was EMS personnel safety. Secondary (important) outcomes were patient safety; personnel performance; acute states of fatigue, alertness, and sleepiness; indicators of sleep duration and/or quality; employee retention/turnover; indicators of long-term health; and cost to the system. Meta-analyses were performed to evaluate the impact of napping on a measure of personnel performance (the psychomotor vigilance test [PVT]) and measures of acute fatigue. Of 4,660 unique records identified, 13 experimental studies were determined relevant and summarized. The effect of napping on reaction time measured at the end of shift was small and non-significant (SMD 0.12, 95% CI -0.13 to 0.36; p = 0.34). Napping during work did not change reaction time from the beginning to the end of the shift (SMD -0.01, 95% CI -25.0 to 0.24; p = 0.96). Naps had a moderate, significant effect on sleepiness measured at the end of shift (SMD 0.40, 95% CI 0.09 to 0.72; p = 0.01). The difference in sleepiness from the start to the end of shift was moderate and statistically significant (SMD 0.41, 95% CI 0.09 to 0.72; p = 0.01). Reviewed literature indicated that scheduled naps at work improved performance and decreased fatigue in shift workers. Further research is required to identify the optimal timing and duration of scheduled naps to maximize the beneficial outcomes.

  11. Value of apparent diffusion coefficient (ADC) in assessing radiotherapy and chemotherapy success in cervical cancer.

    Science.gov (United States)

    Fu, Zhan-Zhao; Peng, Yong; Cao, Li-Yan; Chen, Yan-Sheng; Li, Kun; Fu, Bao-Hong

    2015-06-01

    We investigated the clinical significance of apparent diffusion coefficient (ADC) values in diffusion-weighted magnetic resonance imaging (DWI) in monitoring the efficacy of radiotherapy (RT) and chemotherapy (CT) treatments in cervical cancer. In order to identify relevant high quality clinical cohort studies reporting the use of DWI in cervical cancers, the following electronic databases in English and Chinese languages were comprehensively searched: MEDLINE, Science Citation Index database, Cochrane Library Database, PubMed, Embase, CINAHL, and Current Contents Index; Chinese Biomedical Database, Chinese Journal Full-Text Database. All selected studies were published prior to March 2014, and data extracted from these studies were analyzed using STATA 12.0 statistical software. We initially retrieved 196 articles (79 Chinese articles and 117 English articles) through database searches and finally selected sixteen cohort studies for this meta-analysis. The 16 studies contained a combined total of 517 subjects, and all selected studies reported the mean ADC value (10(-3) mm(2)/s) in DWI in cervical cancer patients treated with RT and CT. Combined standardized mean difference (SMD) suggested that the mean post-RT and mean post-CT ADC values were significantly higher than the mean pre-RT and mean pre-CT ADC values, respectively, in cervical cancer patients (SMD=2.95, 95% CI=2.19-3.72, P900 (SMD=2.55, 95% CI=1.78-3.32, P<0.001). The mean ADC value in patients without residual tumor post-RT and post-CT treatment was significantly higher than seen in patients with residual tumors (SMD=0.80, 95% CI=0.49-1.12, P<0.001). Our meta-analysis revealed a significant correlation between mean ADC values and the clinical response to RT and CT treatment. Thus, ADC values in DWI may be effective in evaluating the clinical outcome of treatments in cervical cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Interventions to Promote Fundamental Movement Skills in Childcare and Kindergarten: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Wick, Kristin; Leeger-Aschmann, Claudia S; Monn, Nico D; Radtke, Thomas; Ott, Laura V; Rebholz, Cornelia E; Cruz, Sergio; Gerber, Natalie; Schmutz, Einat A; Puder, Jardena J; Munsch, Simone; Kakebeeke, Tanja H; Jenni, Oskar G; Granacher, Urs; Kriemler, Susi

    2017-10-01

    Proficiency in fundamental movement skills (FMS) lays the foundation for being physically active and developing more complex motor skills. Improving these motor skills may provide enhanced opportunities for the development of a variety of perceptual, social, and cognitive skills. The objective of this systematic review and meta-analysis was to assess the effects of FMS interventions on actual FMS, targeting typically developing young children. Searches in seven databases (CINAHL, Embase, MEDLINE, PsycINFO, PubMed, Scopus, Web of Science) up to August 2015 were completed. Trials with children (aged 2-6 years) in childcare or kindergarten settings that applied FMS-enhancing intervention programs of at least 4 weeks and meeting the inclusion criteria were included. Standardized data extraction forms were used. Risk of bias was assessed using a standard scoring scheme (Effective Public Health Practice Project-Quality Assessment Tool for Quantitative Studies [EPHPP]). We calculated effects on overall FMS, object control and locomotor subscales (OCS and LMS) by weighted standardized mean differences (SMD between ) using random-effects models. Certainty in training effects was evaluated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation System). Thirty trials (15 randomized controlled trials and 15 controlled trials) involving 6126 preschoolers (aged 3.3-5.5 years) revealed significant differences among groups in favor of the intervention group (INT) with small-to-large effects on overall FMS (SMD between 0.46), OCS (SMD between 1.36), and LMS (SMD between 0.94). Our certainty in the treatment estimates based on GRADE is very low. Although there is relevant effectiveness of programs to improve FMS proficiency in healthy young children, they need to be interpreted with care as they are based on low-quality evidence and immediate post-intervention effects without long-term follow-up.

  13. Affective and enjoyment responses in high intensity interval training and continuous training: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Bruno Ribeiro Ramalho Oliveira

    Full Text Available Previous studies investigating the effects of high intensity interval training (HIIT and moderate intensity continuous training (MICT showed controversial results. The aim of the present study was to systematically review the literature on the effects of HIIT and MICT on affective and enjoyment responses. The PRISMA Statement and the Cochrane recommendation were used to perform this systematic review and the database search was performed using PubMed, Scopus, ISI Web of Knowledge, PsycINFO, and SPORTDiscus. Eight studies investigating the acute affective and enjoyment responses on HIIT and MICT were included in the present systematic review. The standardized mean difference (SMD was calculated for Feeling Scale (FS, Physical Activity Enjoyment Scale (PACES and Exercise Enjoyment Scale (EES. The MICT was used as the reference condition. The overall results showed similar beneficial effects of HIIT on PACES and EES responses compared to MICT with SMDs classified as small (PACES-SMD = 0.49, I2 = 69.3%, p = 0.001; EES-SMD = 0.48, I2 = 24.1%, p = 0.245 while for FS, the overall result showed a trivial effect (FS-SMD = 0.19, I2 = 78.9%, p<0.001. Most of the comparisons performed presented positive effects for HIIT. For the FS, six of 12 comparisons showed beneficial effects for HIIT involving normal weight and overweight-to-obese populations. For PACES, six of 10 comparisons showed beneficial effects for HIIT involving normal weight and overweight-to-obese populations. For EES, six of seven comparisons showed beneficial effects for HIIT also involving normal weight and overweight-to-obese populations. Based on the results of the present study, it is possible to conclude that HIIT exercise may be a viable strategy for obtaining positive psychological responses. Although HIIT exercise may be recommended for obtaining positive psychological responses, chronic studies should clarify the applicability of HIIT for exercise adherence.

  14. Affective and enjoyment responses in high intensity interval training and continuous training: A systematic review and meta-analysis.

    Science.gov (United States)

    Oliveira, Bruno Ribeiro Ramalho; Santos, Tony Meireles; Kilpatrick, Marcus; Pires, Flávio Oliveira; Deslandes, Andréa Camaz

    2018-01-01

    Previous studies investigating the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) showed controversial results. The aim of the present study was to systematically review the literature on the effects of HIIT and MICT on affective and enjoyment responses. The PRISMA Statement and the Cochrane recommendation were used to perform this systematic review and the database search was performed using PubMed, Scopus, ISI Web of Knowledge, PsycINFO, and SPORTDiscus. Eight studies investigating the acute affective and enjoyment responses on HIIT and MICT were included in the present systematic review. The standardized mean difference (SMD) was calculated for Feeling Scale (FS), Physical Activity Enjoyment Scale (PACES) and Exercise Enjoyment Scale (EES). The MICT was used as the reference condition. The overall results showed similar beneficial effects of HIIT on PACES and EES responses compared to MICT with SMDs classified as small (PACES-SMD = 0.49, I2 = 69.3%, p = 0.001; EES-SMD = 0.48, I2 = 24.1%, p = 0.245) while for FS, the overall result showed a trivial effect (FS-SMD = 0.19, I2 = 78.9%, pHIIT. For the FS, six of 12 comparisons showed beneficial effects for HIIT involving normal weight and overweight-to-obese populations. For PACES, six of 10 comparisons showed beneficial effects for HIIT involving normal weight and overweight-to-obese populations. For EES, six of seven comparisons showed beneficial effects for HIIT also involving normal weight and overweight-to-obese populations. Based on the results of the present study, it is possible to conclude that HIIT exercise may be a viable strategy for obtaining positive psychological responses. Although HIIT exercise may be recommended for obtaining positive psychological responses, chronic studies should clarify the applicability of HIIT for exercise adherence.

  15. Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

    Science.gov (United States)

    Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

    2017-06-22

    BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, Pprobiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

  16. Effect of massage therapy on labor pain reduction in primiparous women: A systematic review and meta-analysis of randomized controlled clinical trials in Iran

    Directory of Open Access Journals (Sweden)

    Mehdi Ranjbaran

    2017-01-01

    Full Text Available Background: Pain is a common experience for women during labor. Therefore, pain relief care for mothers during labor is very important. This meta-analysis was conducted to evaluate the efficacy of massage therapy on labor pain reduction in primiparous women. Materials and Methods: In this meta-analysis, the databases of Web of Knowledge, PubMed, Scopus, Cochrane, Iranmedex, Scientific Information Database (SID, and Magiran were searched for published articles in English and Persian language up to January 2016. Among the studies, with regard to the inclusion and exclusion criteria, 10 studies were selected. Data were analyzed by using Stata software version 11, and standard mean difference (SMD of effects of massage therapy was calculated. The heterogeneity among studies was evaluated by the Chi-square based Q-test and I2statistics. Results: The results of Chi-square based on Q-test and I2statistics showed heterogeneity among studies in the latent phase (Q = 63.52, P value < 0.001 and I2 = 87.4%, active phase (Q = 26.42, P value < 0.001, and I2 = 77.3%, and transitional phase (Q = 104.84, P value <0.001, and I2 = 95.2%. Results showed that massage therapy reduces labor pain in the latent phase (SMD = −1.23, 95% CI: −1.73 to −0.74, active phase (SMD = −1.59, 95% CI: −2.06 to −1.12, and transitional phase (SMD = −1.90, 95% CI: −3.09 to −0.71. Conclusions: This study provides valid evidence for the effect of massage therapy in Iran for labor pain relief. Therefore, the use of massage therapy can be recommended in the primiparous women.

  17. Advanced Sensors for TBI

    Science.gov (United States)

    2016-12-01

    SMD-VAC- GP, Virtual Industries) with plastic tip. Then the chip was covered with silicone open-cell foam (0.062” thick, HT -870, Stockwell...the build. 26 We discussed with a sub- contractor in Livermore who might be able to perform the packaging assembly work. Dr. Kotovsky...worked with the sub- contractor on practice assemblies anticipating the new upcoming build. Working through an outside contractor represents an enormous

  18. Advertising as a cue to consume: a systematic review and meta-analysis of the effects of acute exposure to unhealthy food and nonalcoholic beverage advertising on intake in children and adults.

    Science.gov (United States)

    Boyland, Emma J; Nolan, Sarah; Kelly, Bridget; Tudur-Smith, Catrin; Jones, Andrew; Halford, Jason Cg; Robinson, Eric

    2016-02-01

    Several studies have assessed the effects of food and nonalcoholic beverage (hereafter collectively referred to as food) advertising on food consumption, but the results of these studies have been mixed. This lack of clarity may be impeding policy action. We examined the evidence for a relation between acute exposure to experimental unhealthy food advertising and food consumption. The study was a systematic review and meta-analysis of published studies in which advertising exposure (television or Internet) was experimentally manipulated, and food intake was measured. Five electronic databases were searched for relevant publications (SCOPUS, PsycINFO, MEDLINE, Emerald Insight, and JSTOR). An inverse variance meta-analysis was used whereby the standardized mean difference (SMD) in food intake was calculated between unhealthy food advertising and control conditions. Twenty-two articles were eligible for inclusion. Data were available for 18 articles to be included in the meta-analysis (which provided 20 comparisons). With all available data included, the analysis indicated a small-to-moderate effect size for advertising on food consumption with participants eating more after exposure to food advertising than after control conditions (SMD: 0.37; 95% CI: 0.09; 0.65; I(2) = 98%). Subgroup analyses showed that the experiments with adult participants provided no evidence of an effect of advertising on intake (SMD: 0.00; P = 1.00; 95% CI: -0.08, 0.08; I(2) = 8%), but a significant effect of moderate size was shown for children, whereby food advertising exposure was associated with greater food intake (SMD: 0.56; P = 0.003; 95% CI: 0.18, 0.94; I(2) = 98%). Evidence to date shows that acute exposure to food advertising increases food intake in children but not in adults. These data support public health policy action that seeks to reduce children's exposure to unhealthy food advertising. © 2016 American Society for Nutrition.

  19. C-reactive protein alterations in bipolar disorder: a meta-analysis.

    Science.gov (United States)

    Dargél, Aroldo A; Godin, Ophelia; Kapczinski, Flávio; Kupfer, David J; Leboyer, Marion

    2015-02-01

    There is growing evidence that bipolar disorder (BD) is associated with inflammation, including abnormal levels of acute-phase C-reactive protein (CRP). Our meta-analysis was conducted to estimate the size of the association between CRP levels and BD, accounting also for subgroup differences (mood phases and treatment). MEDLINE, EMBASE, PsycINFO, and ISI Web of Science and references of identified articles were searched up to June 2013 using the keywords (bipolar disorder) AND (C-reactive protein OR CRP). English language studies measuring blood levels of CRP in patients with BD and control subjects were selected, 136 abstracts were reviewed, 20 articles retrieved, and 11 studies included. Two independent reviewers extracted data. All studies were included in the primary analyses, and between-group differences for subanalyses were also reported. This meta-analysis was performed using random-effects models. Eleven studies comprising 1,618 subjects were eligible for inclusion. Overall, CRP levels were significantly elevated in patients with BD versus controls (standardized mean difference [SMD] = 0.39; 95% CI, 0.24 to 0.55; P < .0001). CRP levels were significantly higher in manic (SMD = 0.73; 95% CI, 0.44 to 1.02; P < .001) and euthymic (SMD = 0.26; 95% CI, 0.01 to 0.51; P = .04), but not in depressed (SMD = 0.28; 95% CI, -0.17 to 0.73; P = .22) patients with BD compared to controls. CRP levels were unrelated to use of lithium or antipsychotic medication. This meta-analysis supports an association between increased CRP levels and BD. Given that an elevated level of CRP is a marker of low-grade inflammation and a risk factor for cardiovascular and malignant diseases, measurement of CRP level might be relevant to the clinical care of bipolar patients. © Copyright 2015 Physicians Postgraduate Press, Inc.

  20. Soil-transmitted helminth infection, loss of education and cognitive impairment in school-aged children: A systematic review and meta-analysis.

    Science.gov (United States)

    Pabalan, Noel; Singian, Eloisa; Tabangay, Lani; Jarjanazi, Hamdi; Boivin, Michael J; Ezeamama, Amara E

    2018-01-01

    Evidence of an adverse influence of soil transmitted helminth (STH) infections on cognitive function and educational loss is equivocal. Prior meta-analyses have focused on randomized controlled trials only and have not sufficiently explored the potential for disparate influence of STH infection by cognitive domain. We re-examine the hypothesis that STH infection is associated with cognitive deficit and educational loss using data from all primary epidemiologic studies published between 1992 and 2016. Medline, Biosis and Web of Science were searched for original studies published in the English language. Cognitive function was defined in four domains (learning, memory, reaction time and innate intelligence) and educational loss in two domains (attendance and scholastic achievement). Pooled effect across studies were calculated as standardized mean differences (SMD) to compare cognitive and educational measures for STH infected/non-dewormed children versus STH uninfected /dewormed children using Review Manager 5.3. Sub-group analyses were implemented by study design, risk of bias (ROB) and co-prevalence of Schistosoma species infection. Influential studies were excluded in sensitivity analysis to examine stability of pooled estimates. We included 36 studies of 12,920 children. STH infected/non-dewormed children had small to moderate deficits in three domains-learning, memory and intelligence (SMD: -0.44 to -0.27, Ploss/performance in tests of memory, reaction time and innate intelligence (SMD: -0.27 to 0.17, P = 0.18-0.69). Infection-related deficits in learning persisted within design/ROB levels (SMD: -0.37 to -52, Ploss in the developing world may be needed to fully realize the benefit of mass deworming programs.

  1. An Optical Characterization of Atomization in Non-Evaporating Diesel Sprays

    OpenAIRE

    Lockett, R. D.; Jeshani, M.; Makri, K.; Price, R.

    2016-01-01

    High-speed planar laser Mie scattering and Laser Induced Fluorescence (PLIF) was employed for the determination of Sauter Mean Diameter (SMD) distribution in non-evaporating diesel sprays. The effect of rail pressure, distillation profile, and consequent fuel viscosity on the drop size distribution developing during primary and secondary atomization was investigated. Samples of conventional crude-oil derived middle-distillate diesel and light distillate kerosene were delivered into an optical...

  2. Enhancing the Impact of NASA Astrophysics Education and Public Outreach: Using Real NASA Data in the Classroom

    Science.gov (United States)

    Lawton, Brandon L.; Smith, D. A.; SMD Astrophysics E/PO Community, NASA

    2013-01-01

    The NASA Science Education and Public Outreach Forums support the NASA Science Mission Directorate (SMD) and its education and public outreach (E/PO) community in enhancing the coherence, efficiency, and effectiveness of SMD-funded E/PO programs. As a part of this effort, the Astrophysics Forum is coordinating a collaborative project among the NASA SMD astrophysics missions and E/PO programs to create a broader impact for the use of real NASA data in classrooms. Among NASA's major education goals is the training of students in the Science, Technology, Engineering, and Math (STEM) disciplines. The use of real data, from some of the most sophisticated observatories in the world, provide educators an authentic opportunity to teach students basic science process skills, inquiry, and real-world applications of the STEM subjects. The goal of this NASA SMD astrophysics community collaboration is to find a way to maximize the reach of existing real data products produced by E/PO professionals working with NASA E/PO grants and missions in ways that enhance the teaching of the STEM subjects. We present an initial result of our collaboration: defining levels of basic science process skills that lie at the heart of authentic scientific research and national education standards (AAAS Benchmarks) and examples of NASA data products that align with those levels. Our results are the beginning of a larger goal of utilizing the new NASA education resource catalog, NASA Wavelength, for the creation of progressions that tie NASA education resources together. We aim to create an informational sampler that illustrates how an educator can use the NASA Wavelength resource catalog to connect NASA real-data resources that meet the educational goals of their class.

  3. Submerged membrane distillation for seawater desalination

    KAUST Repository

    Francis, Lijo

    2014-08-11

    A submerged membrane distillation (SMD) process for fresh water production from Red Sea water using commercially available hollow fiber membranes has been successfully employed and compared with the conventional direct contact membrane distillation (DCMD) process. The hollow fiber membranes have been characterized for its morphology using field effect scanning electron microscope. In SMD process, a bunch of hollow fiber membranes are glued together at both ends to get a simplified open membrane module assembly submerged into the coolant tank equipped with a mechanical stirrer. Hot feed stream is allowed to pass through the lumen side of the membrane using a feed pump. Continuous stirring at the coolant side will reduce the temperature and concentration polarization. During the conventional DCMD process, using feed-coolant streams with co-current and counter-current flows has been tested and the results are compared in this study. In SMD process, a water vapor flux of 10.2 kg m-2 h-1 is achieved when using a feed inlet temperature of 80°C and coolant temperature of 20°C. Under the same conditions, during conventional DCMD process, a water vapor flux of 11.6 and 10.1 kg m-2 h-1 were observed during counter-current and co-current flow streams, respectively. Results show that the water production in the SMD process is comparable with the conventional DCMD process, while the feed-coolant flow streams are in the co-current direction. During conventional DCMD operation, a 15% increase in the water production is observed when feed-coolant streams are in the counter-current direction compared to the co-current direction. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  4. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    International Nuclear Information System (INIS)

    Mai, Binh Khanh; Li, Mai Suan

    2011-01-01

    Highlights: → We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. → It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. → We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. → The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  5. Oxidative Stress and Sodium Methyldithiocarbamate–Induced Modulation of the Macrophage Response to Lipopolysaccharide In Vivo

    OpenAIRE

    Pruett, Stephen B.; Cheng, Bing; Fan, Ruping; Tan, Wei; Sebastian, Thomas

    2009-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the United States, and hundreds of thousands of persons are exposed to this compound or its major breakdown product, methylisothiocyanate, at levels greater than recommended by the Environmental Protection Agency. A previous study suggests three mechanisms of action involved to some degree in the inhibition of inflammation and decreased resistance to infection caused by exposure of mice to the compo...

  6. Determination of one-electron reduction potentials of some radiosensitive compounds by pulse radiolysis

    International Nuclear Information System (INIS)

    Zuo Zhihua; Yao Side; Li Hucheng; Lin Nianyun; Jin Yizun

    1994-01-01

    One-electron reduction potential (E 7 1 ) is one of the important parameters of radiosensitive compound with high electron affinity. In this work one-electron reduction potentials of some radiosensitizers, such as Miso, 911, CMNa, SMU-1, SMU-2, SMD, SNN, S 3 and BSO, were determined pulse radiolytically by using anthraquinone-2-sulfate (AQS), duroquinone (DQ) and methyl viologen (MV 2+ ) as references

  7. Helminth infections and micronutrients in school-age children: a systematic review and meta-analysis.

    Science.gov (United States)

    de Gier, Brechje; Campos Ponce, Maiza; van de Bor, Margot; Doak, Colleen M; Polman, Katja

    2014-06-01

    Helminth infections and micronutrient deficiencies are highly prevalent in developing countries. Neither condition typically causes overt disease, but they do lead to indirect morbidity such as impaired physical and cognitive development. We aimed to systematically review current evidence on the relation of helminth infections with micronutrient status in school-age children worldwide. We included both observational studies and randomized controlled trials (RCTs). We applied a random-effects meta-analysis to estimate 1) cross-sectional associations between helminths and micronutrient status, 2) effects of anthelminthic treatment on micronutrient status, and 3) effects of micronutrient supplementation on helminth infection and reinfection. Meta-analyses of observational studies showed an association between helminth infections and serum retinol [standardized mean difference (SMD): -0.30; 95% CI: -0.48, -0.13] but not serum ferritin (SMD: 0.00; 95% CI: -0.7, 0.7). Conversely, meta-analyses of anthelminthic treatment RCTs showed a positive effect on ferritin (SMD: 0.16; 95% CI: 0.09, 0.22) but not retinol (SMD: 0.04; 95% CI: -0.06, 0.14). The number of studies on micronutrients other than ferritin and retinol was not sufficient for pooling. Meta-analyses of micronutrient-supplementation RCTs showed only a modest protective effect for multimicronutrient interventions on helminth infection and reinfection rates (OR: 0.77; 95% CI: 0.61, 0.97). In this review, we show evidence of distinct associations between helminth infections and micronutrients in school-age children. More studies are needed on micronutrients other than iron and vitamin A and on possible helminth species-specific effects. A thorough comprehension of the interplay between helminth infections and micronutrients will help guide integrated and sustainable intervention strategies in affected children worldwide. © 2014 American Society for Nutrition.

  8. Psychological Impact of Deploying in Support of the U.S. Response to Ebola: A Systematic Review and Meta-Analysis of Past Outbreaks.

    Science.gov (United States)

    Vyas, Kartavya J; Delaney, Eileen M; Webb-Murphy, Jennifer A; Johnston, Scott L

    2016-11-01

    To examine the potential psychological impact of deploying in support of the U.S. response to Ebola in west Africa by systematic review and meta-analysis. Peer-reviewed articles published between January 2000 and December 2014 were identified using PubMed, PsycINFO, and Web of Science. Thirty-two studies involving 26,869 persons were included in the systematic review; 13 studies involving 7,785 persons were included in the meta-analysis. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Reflecting the sociodemographics of the military, those who are younger, single, not living with family, have fewer years of work experience, lower education, and lower income are at increased risk for psychological distress, alcohol/drug misuse, post-traumatic stress disorder (PTSD), depression, and/or anxiety as a result of their perceived risk of infection. Effect sizes for post-traumatic stress disorder, depressive, and anxiety symptoms were considered small (SMD = 0.12, 95% CI = -0.23 to 0.47), moderate (SMD = 0.40, 95% CI = 0.24-0.51), and small (SMD = 0.08, 95% CI = -0.09 to 0.25), respectively; however, only the effect size for depressive symptoms was statistically significant. Deployed service members may return with clinically significant problems, the most notable of which is depression. Delivering resilience training and fostering altruistic acceptance may protect service members from developing mental health disorders. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  9. Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection

    OpenAIRE

    Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

    2017-01-01

    Abstract Background: The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Results: Six studi...

  10. Browse Title Index

    African Journals Online (AJOL)

    Items 551 - 600 of 823 ... Vol 22, No 1 (2017), Pin tract infection after uniplanar external fixation of open fractures at a national, teaching and referral hospital, Abstract PDF. R.M. Mohammed, E.O. Atinga, F.C. Sitati, E.M. .... SMD Muwazi, M Knwooya, S Oola, JWM Kiryabwire, D Iga-Matow. Vol 15, No 1 (2010), Primary Splenic ...

  11. Proceedings of the First International Symposium on the Interaction of Non-Nuclear Munitions with Structures: Held at U.S. Air Force Academy, Colorado on May 10-13, 1983. Part 1.

    Science.gov (United States)

    1983-05-01

    concrete has boe made free which a characteristics of reinforced concrete comprehesiave elscttc- platic -fracturo materials do met cest, the problem of strese...pig. 1. stress smd strot% reletionship to assemd so defia., the plastic behaviors. The platic relecios are developed es the heeis of a e*iedetjpj9 rule...computer - elasto- platic formulation for concrete in co! prorram with more confidence. preesion. Based on the well-cstablished theory of plasticity, the

  12. Kelle rahanõuandeid kuulate ja kasutate?

    Index Scriptorium Estoniae

    2005-01-01

    Küsimusele vastavad vabakutseline kirjanik Kadri Kõusaar, Riigikogu liige Andres Lipstok, TTÜ üliõpilasesinduse juhatuse esimees Heiki Lemba, IM Arvutite sekretär-raamatupidaja Silja Kalda, Vain SMD konsultant ja koolitaja Urmas Purde, energeetik Peeter Saeraas, Euro Painting and Restoration juht Brian Sepp, Mercuri Urval konsultant Tarmo Müürsepp, Regio osakonnajuhataja Gerri Kodres, OÜ Vastus juht Jelena Rootamm-Valter

  13. Hypnotherapy for insomnia: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Lam, Tak-Ho; Chung, Ka-Fai; Yeung, Wing-Fai; Yu, Branda Yee-Man; Yung, Kam-Ping; Ng, Tommy Ho-Yee

    2015-10-01

    To examine the efficacy and safety of hypnotherapy for insomnia as compared to placebo, pharmacological or non-pharmacological intervention, or no treatment. A systematic search on major electronic databases was conducted up until March 2014. Inclusion criteria are: (1) randomized controlled trials (RCTs) or quasi-RCTs; (2) intervention targeted at improving sleep; (3) hypnosis as an intervention; and (4) English language articles. Sleep diary variable is the primary outcome measure. Six RCTs of hypnotherapy and seven on autogenic training or guided imagery, comprising 502 subjects, were included. Eleven of the 13 studies had low methodological quality, as indicated by a modified Jadad score below 3, and high risks of bias in blinding and design of the control interventions. No adverse events related to hypnosis were reported, though seldom investigated. Meta-analyses found hypnotherapy significantly shortened sleep latency compared to waitlist (standardized mean difference, SMD=-0.88, 95% confidence interval (CI): -1.56, -0.19, P=0.01, I(2)=15%), but no difference compared to sham intervention (SMD: -1.08, 95% CI: -3.15, 0.09, P=0.31, I(2)=90%). Similar results were found for autogenic training or guided imagery (SMD with waitlist=-1.16, 95% CI: -1.92, -0.40, P=0.003, I(2)=0%; SMD with sham intervention=-0.50, 95% CI: -1.19, 0.19, P=0.15, I(2)=0%). Generalizability of the positive results is doubtful due to the relatively small sample size and methodological limitations. Future studies with larger sample size and better study design and methodology are called for. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. NASA Astrophysics Technology Needs

    Science.gov (United States)

    Stahl, H. Philip

    2012-01-01

    July 2010, NASA Office of Chief Technologist (OCT) initiated an activity to create and maintain a NASA integrated roadmap for 15 key technology areas which recommend an overall technology investment strategy and prioritize NASA?s technology programs to meet NASA?s strategic goals. Science Instruments, Observatories and Sensor Systems(SIOSS) roadmap addresses technology needs to achieve NASA?s highest priority objectives -- not only for the Science Mission Directorate (SMD), but for all of NASA.

  15. Homeopathy in the treatment of fibromyalgia--a comprehensive literature-review and meta-analysis.

    Science.gov (United States)

    Boehm, Katja; Raak, Christa; Cramer, Holger; Lauche, Romy; Ostermann, Thomas

    2014-08-01

    Coping with the complex nature of fibromyalgia symptoms (FMS) still remains a challenge for patients. Taking into account the possible adverse events of pharmacological treatments patients often seek additional treatments for the management of fibromyalgia and turn towards complementary and alternative medicine (CAM). In this review, we aimed to investigate the current state of literature of homeopathy in the treatment of FMS. We searched Medline, the Cochrane Register of Controlled Trials, Embase, AMED, PsycInfo and CAMbase for the terms "fibromyalgia AND homeopath$" through February 2013. In addition we searched Google Scholar, the library of the Carstens Foundation and that of the Deutsche Homöopathische Union (DHU). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated and meta-analyzed using the generic inverse variance method. We found 10 case-reports, 3 observational studies, 1 non-randomized and 4 randomized controlled trials (RCTs) on homeopathy for fibromyalgia. Both case reports and observational studies are naturally predominated by the use of qualitative and not validated outcome measures. Meta-analyses of CCTs revealed effects of homeopathy on tender point count (SMD=-0.42; 95%CI -0.78, -0.05; P=0.03), pain intensity (SMD=-0.54; 95%CI -0.97, -0.10; P=0.02), and fatigue (SMD=-0.47; 95%CI -0.90, -0.05; P=0.03) compared to placebo. The results of the studies as well as the case reports define a sufficient basis for discussing the possible benefits of homeopathy for patients suffering from fibromyalgia syndrome although any conclusions based on the results of this review have to be regarded as preliminary. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Constraint-induced movement therapy improves upper limb activity and participation in hemiplegic cerebral palsy: a systematic review

    Directory of Open Access Journals (Sweden)

    Hsiu-Ching Chiu

    2016-07-01

    Full Text Available Questions: Does constraint-induced movement therapy improve activity and participation in children with hemiplegic cerebral palsy? Does it improve activity and participation more than the same dose of upper limb therapy without restraint? Is the effect of constraint-induced movement therapy related to the duration of intervention or the age of the children? Design: Systematic review of randomised trials with meta-analysis. Participants: Children with hemiplegic cerebral palsy with any level of motor disability. Intervention: The experimental group received constraint-induced movement therapy (defined as restraint of the less affected upper limb during supervised activity practice of the more affected upper limb. The control group received no intervention, sham intervention, or the same dose of upper limb therapy. Outcome measures: Measures of upper limb activity and participation were used in the analysis. Results: Constraint-induced movement therapy was more effective than no/sham intervention in terms of upper limb activity (SMD 0.63, 95% CI 0.20 to 1.06 and participation (SMD 1.21, 95% CI 0.41 to 2.02. However, constraint-induced movement therapy was no better than the same dose of upper limb therapy without restraint either in terms of upper limb activity (SMD 0.05, 95% CI –0.21 to 0.32 or participation (SMD –0.02, 95% CI –0.34 to 0.31. The effect of constraint-induced movement therapy was not related to the duration of intervention or the age of the children. Conclusions: This review suggests that constraint-induced movement therapy is more effective than no intervention, but no more effective than the same dose of upper limb practice without restraint. Registration: PROSPERO CRD42015024665. [Chiu H-C, Ada L (2016 Constraint-induced movement therapy improves upper limb activity and participation in hemiplegic cerebral palsy: a systematic review. Journal of Physiotherapy 62: 130–137

  17. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Lin, Yu-Ching; Wu, Wei-Ting; Hsu, Yu-Chun; Han, Der-Sheng; Chang, Ke-Vin

    2018-02-01

    To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.

  18. Effects of Group Counseling Programs, Cognitive Behavioral Therapy, and Sports Intervention on Internet Addiction in East Asia: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Liu, Jun; Nie, Jing; Wang, Yafeng

    2017-11-28

    To evaluate the effects of group counseling programs, cognitive behavioral therapy (CBT), and sports intervention on Internet addiction (IA), a systematic search in ten databases was performed to identify eligible studies without language restrictions up to January 2017. A meta-analysis and trial sequential analysis (TSA) was performed, respectively. A total of 58 randomized controlled trials (RCTs), which included 2871 participants, were incorporated into our meta-analysis. The results showed that group counseling programs, CBT, and sports intervention could significantly reduce IA levels (group counseling program: standardized mean difference (SMD), -1.37; 95% confidence interval (CI), -1.89 to -0.85; CBT: SMD, -1.88; 95% CI, -2.53 to -1.23; sports intervention: SMD, -1.70; 95% CI, -2.14 to -1.26). For group counseling programs, this treatment was more effective in four dimensions of IA, including time management, interpersonal and health issues, tolerance, and compulsive Internet use. For CBT, this treatment yielded a positive change in depression, anxiousness, aggressiveness, somatization, social insecurity, phobic anxiety, paranoid ideation, and psychoticism. For sports intervention, the significant effects were also observed in all dimensions of the IA scale. Each of group counseling programs, cognitive behavioral therapy, and sports intervention had a significant effect on IA and psychopathological symptoms. Sports intervention could improve withdrawal symptoms especially.

  19. Meta-analysis of clinical trials on traditional Chinese herbal medicine for treatment of persistent allergic rhinitis.

    Science.gov (United States)

    Wang, Shijun; Tang, Qiaofei; Qian, Wei; Fan, Yu

    2012-05-01

    Chinese herbal medicine (CHM) has been used for the prevention and treatment of persistent allergic rhinitis (PAR), but results are still equivocal. This study was to assess the clinical effectiveness of CHM in patients with PAR. Databases searched included articles published in the Cochrane library, MEDLINE, EMBASE, China National Knowledge Infrastructure, and Wanfang database from 1999 to 2011. The studies included were randomized controlled trials (RCTs) comparing CHM to placebo if they included patients with PAR. The main outcomes were the changes in the standardized mean difference (SMD) of nasal symptom scores and total serum IgE level. Methodological quality was assessed by the modified Jadad's scale. Seven RCTs with 533 patients were identified and analyzed. In the meta-analysis, CHM reduced the total nasal symptom scores compared to placebo (SMD, -1.82; 95% confidence interval [CI], -3.03 to -0.62; P = 0.003). The effect estimate was in favor of the CHM intervention (SMD, -1.09; 95% CI, -2.74 to 0.55) in reducing the total serum IgE level, although this was not significant (P = 0.19). CHM interventions appear to have beneficial effects in patients with PAR. However, the published efficacy studies are too small to draw firm conclusion. © 2012 John Wiley & Sons A/S.

  20. Radial distributions of surface mass density and mass-to-luminosity ratio in spiral galaxies

    Science.gov (United States)

    Sofue, Yoshiaki

    2018-03-01

    We present radial profiles of the surface mass density (SMD) in spiral galaxies directly calculated using rotation curves of two approximations of flat-disk (SMD-F) and spherical mass distribution (SMD-S). The SMDs are combined with surface brightness using photometric data to derive radial variations of the mass-to-luminosity ratio (ML). It is found that the ML generally has a central peak or a plateau, and decreases to a local minimum at R ˜ 0.1-0.2 h, where R is the radius and h is the scale radius of optical disk. The ML, then, increases rapidly until ˜0.5 h, and is followed by gradual rise till ˜2 h, remaining at around ˜2 [M_{⊙} L^{-1}_{⊙}] in the w1 band (infrared λ3.4 μm) and ˜ 10 [M_⊙ L_⊙ ^{-1}] in the r band (λ6200-7500 Å). Beyond this radius, the ML increases steeply with approaching the observed edges at R ˜ 5 h, attaining to as high values as ˜20 in w1 and ˜ 10^2 [M_⊙ L_⊙ ^{-1}] in the r band, which are indicative of dominant dark matter. The general properties of the ML distributions will be useful for constraining cosmological formation models of spiral galaxies.

  1. Impact of Early Enteral Nutrition on Nutritional and Immunological Outcomes of Gastric Cancer Patients Undergoing Gastrostomy: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Nikniaz, Zeinab; Somi, Mohammad Hossein; Nagashi, Shahnaz; Nikniaz, Leila

    2017-07-01

    The present systematic review and meta-analysis study evaluated the impact of early enteral nutrition (EN) on postoperative nutritional and immunological outcomes of gastric cancer (GC) patients. The databases of PubMed, Embase, Springer, and Cochrane library were searched till September 2016 to identify studies which evaluated the effects of EN compared with parenteral nutrition (PN) on postoperative immunological and nutritional status and hospitalization time in GC patients. Mean difference (MD) or standard mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. The present systematic review and meta-analysis have consisted of seven trials, containing 835 GC patients. According to the result of meta-analysis, compared with PN, EN significantly resulted in more increase in the level of albumin [MD = 2.07 (0.49, 3.64)], prealbumin [MD = 9.41 (049, 33.55)], weight [MD = 1.52 (0.32, 2.72)], CD3+ [SMD = 1.96 (1.50, 2.43)], CD4+ [SMD = 2.45 (1.97, 2.93)], natural killers [MD = 5.80 (3.75, 7.85)], and also a decrease in the hospitalization time [MD=-2.39 (-2.74, -2.03)]. The results demonstrated that early administration of EN is more effective in improving postsurgical nutrition status and immune index in GC patients. So, based on these results, postoperative early administration of EN is recommended for GC patients where possible.

  2. Annual report for the High Energy Physics Program at The University of Alabama

    International Nuclear Information System (INIS)

    Baksay, L.; Busenitz, J.K.

    1993-10-01

    The High Energy Physics group at University of Alabama is a member of the L3 collaboration studying e + e - collisions near the Z degree pole at the LEP accelerator at CERN. About 2 million Z degree events have been accumulated and the experiment has been prolific in publishing results on the Z resonance parameters, the Z couplings to all leptons and quarks with mass less than half the Z mass, searches for new particles and interactions, and studies of strong interactions and/or weak charged current decays of quarks and leptons abundantly produced in Z decays. They are contributing to data analysis as well as to detector hardware. In particular, they are involved in a major hardware upgrade for the experiment, namely the design, construction and commissioning of a Silicon Microvertex Detector (SMD) which has successfully been installed for operation during the present grant period. A report is presented on their recent L3 activities and their plans for the next grant period of twelve months (April 1, 1994--March 31, 1995). Their main interests in data analysis are in the study of single photon final states and the physics made more accessible by the SMD, such as heavy flavor physics. Their hardware efforts continue to be concentrated on the high precision capacitive and optical alignment monitoring systems for the SMD and also includes gas monitoring for the muon system. They are also planning to participate in the coming upgrade of the L3 detector

  3. Study of Near-Cup Droplet Breakup of an Automotive Electrostatic Rotary Bell (ESRB Atomizer Using High-Speed Shadowgraph Imaging

    Directory of Open Access Journals (Sweden)

    Jacob E. Wilson

    2018-05-01

    Full Text Available Electrostatic Rotary bell (ESRB atomizers are used as the dominant means of paint application by the automotive industry. They utilize the high rotational speed of a cup to induce primary atomization of a liquid along with shaping air to provide secondary atomization and transport. In order to better understand the fluid breakup mechanisms involved in this process, high-speed shadowgraph imaging was used to visualize the edge of a serrated rotary bell at speeds varying between 5000 and 12,000 RPM and with a water flow rate of 250 ccm. A multi-step image processing algorithm was developed to differentiate between ligaments and droplets during the primary atomization process. The results from this experiment showed that higher bell speeds resulted in a 26.8% reduction in ligament and 22.3% reduction in droplet Sauter Mean Diameters (SMD. Additionally, the ligament (ranging from 40 to 400 μm diameters formed bimodal distributions, while the droplet (ranging from 40 to 300 μm diameters formed a normal distribution. Velocities were also measured using particle tracking velocimetry, in which size-dependent velocities could then be computed. Droplet velocities were affected more by rotational speed than droplet SMD, while ligaments were affected by other factors than the rotational speed and ligament SMD.

  4. Pharmacotherapy of retinal disease with visual cycle modulators.

    Science.gov (United States)

    Hussain, Rehan M; Gregori, Ninel Z; Ciulla, Thomas A; Lam, Byron L

    2018-04-01

    Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies. Expert opinion: Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.

  5. Effect of food on specific dynamic action (SDA) of green and red types of sea cucumber ( Apostichopus japonicus Selenka)

    Science.gov (United States)

    Bao, Jie; Jiang, Hongbo; Dong, Shuanglin; Tian, Xiangli

    2017-10-01

    Specific dynamic action (SDA), the energy expended on all physiological processes that is associated with meal digestion and absorption, is strongly affected by food type. Effects of formulated diet (FMD), macroalgae (ALG) and sea mud (SMD) diets on the postprandial metabolic response of the green type and the red type of sea cucumber ( Apostichopus japonicus) were studied in order to understand their feeding physiology. Food offered to A. japonicus was different in protein, lipid content and energy but not in meal mass. SDA of A. japonicus resulted in a 1.3-2.7 folds of increase in oxygen consumption that can persist for up to 4.8-31.7 h after digesting three different diets. In a given type of sea cucumber, the magnitude of SDA was the highest when fed with FMD, medium with ALG, and the lowest with SMD, which is probably due to the differences in diet components and protein contents. The red type sea cucumber showed greater SDA magnitude than the green type with each diet treatment, which might result from the difference in factorial scope between the two types of sea cucumber. However, the smallest magnitude or even no difference was observed between the two types of A. japonicus in SMD group, perhaps owing to the poor nutrition and digestion of sea mud.

  6. [High Energy Physics Program at the University of Alabama. Final report

    International Nuclear Information System (INIS)

    Baksay, L.; Busenitz, J.K.

    1993-10-01

    The High Energy Physics group at University of Alabama is a member of the L3 collaboration studying e+e- collisions near the Z degree pole at the LEP accelerator at CERN. About 2 million Z degree events have been accumulated and the experiment has been prolific in publishing results on the Z resonance parameters, the Z couplings to all leptons and quarks with mass less than half the Z mass, searches for new particles and interactions, and studies of strong interactions and/or weak charged current decays of the quarks and leptons abundantly produced in Z decays. The group is contributing to data analysis as well as to detector hardware. In particular, the authors are involved in a major hardware upgrade for the experiment, namely the design, construction and commissioning of a Silicon Microvertex Detector (SMD) which has successfully been installed for operation during the present grant period. The authors present here a report on their recent L3 activities and their plans for the next grant period of twelve months (April 1, 1994--March 31, 1995). Their main interests in data analysis are in the study of single photon final states and the physics made more accessible by the SMD, such as heavy flavor physics. Their hardware efforts continue to be concentrated on the high precision capacitive and optical alignment monitoring systems for the SMD and also includes gas monitoring for the muon system. They are also planning to participate in the coming upgrade of the L3 detector

  7. Standardized mean differences cause funnel plot distortion in publication bias assessments.

    Science.gov (United States)

    Zwetsloot, Peter-Paul; Van Der Naald, Mira; Sena, Emily S; Howells, David W; IntHout, Joanna; De Groot, Joris Ah; Chamuleau, Steven Aj; MacLeod, Malcolm R; Wever, Kimberley E

    2017-09-08

    Meta-analyses are increasingly used for synthesis of evidence from biomedical research, and often include an assessment of publication bias based on visual or analytical detection of asymmetry in funnel plots. We studied the influence of different normalisation approaches, sample size and intervention effects on funnel plot asymmetry, using empirical datasets and illustrative simulations. We found that funnel plots of the Standardized Mean Difference (SMD) plotted against the standard error (SE) are susceptible to distortion, leading to overestimation of the existence and extent of publication bias. Distortion was more severe when the primary studies had a small sample size and when an intervention effect was present. We show that using the Normalised Mean Difference measure as effect size (when possible), or plotting the SMD against a sample size-based precision estimate, are more reliable alternatives. We conclude that funnel plots using the SMD in combination with the SE are unsuitable for publication bias assessments and can lead to false-positive results.

  8. A systematic review and meta-analysis comparing combined intravenous and topical tranexamic acid with intravenous administration alone in THA.

    Directory of Open Access Journals (Sweden)

    Yangbai Sun

    Full Text Available To compare the effectiveness and safety of combined intravenous and topical tranexamic acid with intravenous use alone in THA.The electronic databases MEDLINE, EMBASE, BIOSIS, Cochrane central, and further adapted for Google and Google Scholar internet, last updated on Dec 30, 2016, were searched. Evaluated outcomes included total blood loss, transfusion rate, maximum postoperative Hb drop, and incidence of thromboembolic complications. The standard mean difference (SMD or the relative risk (RR was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration's RevMan 5.0 software.Five RCTs with 457 patients were included. Combined TXA administration reduced blood loss (SMD, 1.39; 95%CI, 0.55 to 2.23; P<0.00001, I2 = 94%, hemoglobin decline (SMD, 0.84; 95%CI, 0.13 to 1.54; P = 0.01, I2 = 83% and the need for transfusion (RR, 2.58; 95%CI, 1.59 to 4.18; P = 0.65, I2 = 0% without increasing the rate of thromboembolic complications significantly (RR, 0.83; 95%CI, 0.27 to 2.54; P = 0.81, I2 = 0%.The present study has emphasized that combined TXA administration can effectively reduce blood loss, hemoglobin decline and the need for transfusion without increasing the rate of thromboembolic complications.

  9. A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients.

    Science.gov (United States)

    Bushe, Chris; Day, Kathleen; Reed, Victoria; Karlsdotter, Kristina; Berggren, Lovisa; Pitcher, Ashley; Televantou, Foula; Haynes, Virginia

    2016-05-01

    The lack of head-to-head clinical studies powered to compare atomoxetine and osmotic release oral system (OROS) methylphenidate necessitates treatment comparison by methods that include indirect evidence such as network meta-analysis (NMA). A NMA assessing the relative treatment effects of atomoxetine and OROS methylphenidate in adults with attention-deficit/hyperactivity disorder (ADHD) was conducted. Studies were identified by systematic literature review. Analyses summarised improvements in efficacy, measured by ADHD-specific scales, using Cohen'sdto calculate the standardised mean difference (SMD), and all cause discontinuations. Results showed effect sizes (SMD, 95% credible interval (CrI)) relative to placebo that did not differ significantly between atomoxetine (0.46, 0.36-0.56) and OROS methylphenidate (0.51, 0.40-0.63) in clinical studies of up to 12 weeks' duration (SMD, 95% CrI for atomoxetine versus OROS methylphenidate: -0.05, -0.18-0.08). Patients treated with these medications responded better than those given placebo across all analyses. There was also no significant difference in discontinuation rates between atomoxetine and OROS methylphenidate (odds ratio, 95% CrI: 0.85, 0.53-1.35). Between-study heterogeneity was low overall. Results of this NMA suggest that the efficacy of atomoxetine and OROS methylphenidate in adults does not differ significantly. Clinical guidelines may require amendment to reflect these recent data. © The Author(s) 2016.

  10. Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator

    Directory of Open Access Journals (Sweden)

    Satoshi Miyamoto

    2016-05-01

    Full Text Available AMP-activated protein kinase (AMPK is suppressed in diabetes and may be due to a high ATP/AMP ratio, however the quantitation of nucleotides in vivo has been extremely difficult. Via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI to localize renal nucleotides we found that the diabetic kidney had a significant increase in glomerular ATP/AMP ratio. Untargeted MALDI-MSI analysis revealed that a specific sphingomyelin species (SM(d18:1/16:0 accumulated in the glomeruli of diabetic and high-fat diet-fed mice compared with wild-type controls. In vitro studies in mesangial cells revealed that exogenous addition of SM(d18:1/16:0 significantly elevated ATP via increased glucose consumption and lactate production with a consequent reduction of AMPK and PGC1α. Furthermore, inhibition of sphingomyelin synthases reversed these effects. Our findings suggest that AMPK is reduced in the diabetic kidney due to an increase in the ATP/AMP ratio and that SM(d18:1/16:0 could be responsible for the enhanced ATP production via activation of the glycolytic pathway.

  11. Study of higher order modes in superconducting accelerating structures for linac applications

    Energy Technology Data Exchange (ETDEWEB)

    Schuh, Marcel

    2011-06-22

    Higher Order Modes (HOMs) can severely limit the operation of superconducting cavities in a linear accelerator with high beam current, high duty factor and complex pulse structure. Therefore, the full HOM spectrum has to be analysed in detail to identify potentially dangerous modes already during the design phase and to define their damping requirements. For this purpose a dedicated beam dynamics simulation code, Simulation of higher order Mode Dynamics (SMD), focusing on beam-HOM interaction, has been developed in the frame of this project. SMD allows to analyse the beam behaviour under the presence of HOMs, taking into account many important effects, such as for example the HOM frequency spread, beam input jitter, different chopping patterns, as well as klystron and alignment errors. SMD is used to investigate in detail into the effects of HOMs in the Superconducting Proton Linac (SPL) at CERN and in particular their potential to drive beam instabilities in the longitudinal and transverse direction. Based on these results, HOM damping requirements for the HOM coupler design are then defined. In addition, the linear accelerators of the European Spallation Source (ESS) and the Spallation Neutron Source (SNS) are analysed with respect to HOM impact and the results are compared with the SPL simulations. (orig.)

  12. Correlation between interleukin-6 and primary hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    LI Xia

    2015-06-01

    Full Text Available ObjectiveTo evaluate the correlation between interleukin (IL6 and primary hepatocellular carcinoma (HCC. MethodsCase-control studies that included quantitative data on plasma or serum IL-6 levels of patients with HCC were identified from PubMed, ISI Web of Knowledge, CBM, and CNKI. A meta-analysis was performed to quantitatively and comprehensively analyze data. ResultsTwenty-five studies were included and the meta-analysis was conducted separately for 3 groups: HCC vs controls, HCC vs liver cirrhosis, and HCC vs hepatitis. The serum IL-6 levels of patients with HCC were significantly higher than those of healthy controls (25 studies, standardized mean difference (SMD 5.02, 95% CI: 4.13-5.91, Z=11.05, P<0.000 1, patients with liver cirrhosis (15 studies, SMD=236, 95% CI: 1.54-3.19, Z=5.60, P<0.000 1, and patients with hepatitis (7 studies, SMD=2.63, 95% CI: 1.24-4.03, Z=369, P=0.000 2. ConclusionThe inflammatory mediator, IL-6, may play an important role in the development and progression of HCC.

  13. Emollients and moisturisers for eczema

    DEFF Research Database (Denmark)

    van Zuuren, Esther J; Fedorowicz, Zbys; Christensen, Robin

    2017-01-01

    -quality evidence), satisfaction (one study, 50 participants, RR 1.06, 95% CI 0.74 to 1.52; very low-quality evidence), and investigator-assessed disease severity (three studies, 272 participants, standardised mean difference (SMD) -0.23, 95% CI -0.66 to 0.21; low-quality evidence). In the oat group, there were...... (seven studies, 749 participants, SMD -1.10, 95% CI -1.83 to -0.38) than control. Participants in both treatment arms reported comparable satisfaction (three studies, 296 participants, RR 1.35, 95% CI 0.77 to 2.26; low-quality evidence). Moisturisers led to lower investigator-assessed disease severity...... (12 studies, 1281 participants, SMD -1.04, 95% CI -1.57 to -0.51; high-quality evidence) and fewer flares (six studies, 607 participants, RR 0.33, 95% CI 0.17 to 0.62; moderate-quality evidence), but there was no difference in adverse events (10 studies, 1275 participants, RR 1.03, 95% CI 0.82 to 1...

  14. Plasmonics and single-molecule detection in evaporated silver-island films

    Energy Technology Data Exchange (ETDEWEB)

    Moula, G.; Aroca, R.F. [Materials and Surface Science Group, University of Windsor, Ontario (Canada); Rodriguez-Oliveros, R.; Sanchez-Gil, J.A. [Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientificas, Serrano 121, 28006 Madrid (Spain); Albella, P. [Centro de Fisica de Materiales (CSIC-UPV/EHU) and Donostia International Physics Center (DIPC), 20018 Donostia, San Sebastian (Spain)

    2012-11-15

    The plasmonic origin of surface-enhanced Raman scattering (SERS) leads to the concept of hotspots and plasmon coupling that can be realized in the interstitial regions, or on specially engineered, silver and gold nanostructures. It is also possible to achieve spatial locations of high local field or hotspots on silver-island films (SIF) allowing single-molecule detection (SMD). When a single monomolecular layer coating the SIFs contains dye molecules dispersed in it, single-molecule impurities, (with an average of one hundred dye molecules in 1 {mu}m{sup 2}, which is the field of view of the micro-Raman system), SMD is observed as a rare statistical event. Here, the SMD results for silver-island films are presented, with the same nominal mass thickness, but differing in the localized surface plasmon resonance that is a function of the temperature of substrate during deposition. A blue-shifted plasmon can be seen as a decrease in plasmon coupling for deposition at higher temperature. A simple two-particle model for localized plasmon resonance coupling calculations, including the shape and substrate effects seems to explain the trend of observations. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  15. The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Adam Dinoff

    Full Text Available The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain-derived neurotrophic factor (BDNF mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood.MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions ≥ 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses.In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17-0.60, p < 0.001. Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33-0.99, p < 0.001 but not resistance training (SMD = 0.07, 95% CI: -0.15-0.30, p = 0.52 interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma.Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood.

  16. Interventions for addressing low balance confidence in older adults: a systematic review and meta-analysis.

    Science.gov (United States)

    Rand, Debbie; Miller, William C; Yiu, Jeanne; Eng, Janice J

    2011-05-01

    low balance confidence is a major health problem among older adults restricting their participation in daily life. to determine what interventions are most effective in increasing balance confidence in older adults. systematic review with meta-analysis of randomised controlled trials including at least one continuous end point of balance confidence. Studies, including adults 60 years or older without a neurological condition, were included in our study. the standardised mean difference (SMD) of continuous end points of balance confidence was calculated to estimate the pooled effect size with random-effect models. Methodological quality of trials was assessed using the Physical Therapy Evidence Database (PEDro) Scale. thirty studies were included in this review and a meta-analysis was conducted for 24 studies. Interventions were pooled into exercise (n = 9 trials, 453 subjects), Tai Chi (n = 5 trials, 468 subjects), multifactorial intervention (n = 10 trials, 1,233 subjects). Low significant effects were found for exercise and multifactorial interventions (SMD 0.22-0.31) and medium (SMD 0.48) significant effects were found for Tai Chi. Tai chi interventions are the most beneficial in increasing the balance confidence of older adults.

  17. Spatio-temporal droplet size statistics in developing spray of starchy solution

    Science.gov (United States)

    Naz, Muhammad Yasin; Sulaiman, Shaharin Anwar; Ariwahjoedi, Bambang

    2015-07-01

    In the given research, the spray jet breakup of a modified starch solution was studied as a function of jet injection time and nozzle orifice diameter. The starch-urea-borax solution was prepared and tested with three axisymmetric full cone nozzles at service temperature of 80°C and the injection pressure of 5 bar. It is worth mentioning that no jet breakup was seen below these temperature and pressure values. The imaging studies on the time based spray evolution revealed monotonic increase in both; spray cone angle and tip penetration with an increase in injection time form 0-300 mm. Hereinafter, both parameters exhibited constants value over injection time. Phase Doppler Anemometry (PDA) measurements of the droplet size revealed significant decrease in the Sauter Mean Diameter (SMD) along the spray centerline. However, a steady decrease in SMD was seen towards the spray boundary. For fixed injection time of 300 ms, the overall SMD was decreased from 112 to 71 µm at 60 mm downstream, from 102 to 64 µm at 100 mm downstream and from 85 to 61 µm at 140 mm downstream with an increase in orifice diameter from 1.19 to 1.59 mm.

  18. Effects of Group Counseling Programs, Cognitive Behavioral Therapy, and Sports Intervention on Internet Addiction in East Asia: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2017-11-01

    Full Text Available To evaluate the effects of group counseling programs, cognitive behavioral therapy (CBT, and sports intervention on Internet addiction (IA, a systematic search in ten databases was performed to identify eligible studies without language restrictions up to January 2017. A meta-analysis and trial sequential analysis (TSA was performed, respectively. A total of 58 randomized controlled trials (RCTs, which included 2871 participants, were incorporated into our meta-analysis. The results showed that group counseling programs, CBT, and sports intervention could significantly reduce IA levels (group counseling program: standardized mean difference (SMD, −1.37; 95% confidence interval (CI, −1.89 to −0.85; CBT: SMD, −1.88; 95% CI, −2.53 to −1.23; sports intervention: SMD, −1.70; 95% CI, −2.14 to −1.26. For group counseling programs, this treatment was more effective in four dimensions of IA, including time management, interpersonal and health issues, tolerance, and compulsive Internet use. For CBT, this treatment yielded a positive change in depression, anxiousness, aggressiveness, somatization, social insecurity, phobic anxiety, paranoid ideation, and psychoticism. For sports intervention, the significant effects were also observed in all dimensions of the IA scale. Each of group counseling programs, cognitive behavioral therapy, and sports intervention had a significant effect on IA and psychopathological symptoms. Sports intervention could improve withdrawal symptoms especially.

  19. Effects of exercise programs on depressive symptoms, quality of life, and self-esteem in older people: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Park, Seong-Hi; Han, Kuem Sun; Kang, Chang-Bum

    2014-11-01

    This study attempted to show evidence of exercise programs as intervention to decrease depressive symptoms and to improve quality of life and self-esteem in older people. Systematic review of randomized controlled trials. Electronic databases of KoreaMed, Korea Scientific and Technological Intelligence Center, Korean Society of Nursing Science, Korean Academy of Psychiatric Mental Health Nursing, Ovid-Medline and Embase were searched up to May 25th, 2012 for relevant articles. We searched studies of randomized controlled trials involving exercise programs administered to participants aged 65 years or over. Of 461 publications identified, 18 met the inclusion criteria for the meta-analysis. Quality assessment of the studies utilized Cochrane's Risk of Bias. Exercise therapy in older people was effective, as evidenced by a decrease in depressive symptoms [standardized mean difference (SMD) -0.36; 95% confidence interval (CI) -0.64, -0.08], and improvements in quality of life (SMD 0.86; 95% CI 0.11, 1.62) and self-esteem (SMD 0.49; 95% CI 0.09, 0.88). The changes were significant statistically, with no heterogeneity. Exercise programs in older people are effective in improving depressive symptoms, quality of life and self-esteem. Development and efficient use of tailored exercise programs for elderly people is a prudent strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Enhanced Light Absorption in Fluorinated Ternary Small-Molecule Photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Eastham, Nicholas D. [Department; Dudnik, Alexander S. [Department; Harutyunyan, Boris [Department; Aldrich, Thomas J. [Department; Leonardi, Matthew J. [Department; Manley, Eric F. [Department; Chemical; Butler, Melanie R. [Department; Harschneck, Tobias [Department; Ratner, Mark A. [Department; Chen, Lin X. [Department; Chemical; Bedzyk, Michael J. [Department; Department; Melkonyan, Ferdinand S. [Department; Facchetti, Antonio [Department; Chang, Robert P. H. [Department; Marks, Tobin J. [Department; Department

    2017-06-14

    Using small-molecule donor (SMD) semiconductors in organic photovoltaics (OPVs) has historically afforded lower power conversion efficiencies (PCEs) than their polymeric counterparts. The PCE difference is attributed to shorter conjugated backbones, resulting in reduced intermolecular interactions. Here, a new pair of SMDs is synthesized based on the diketopyrrolopyrrole-benzodithiophene-diketopyrrolopyrrole (BDT-DPP2) skeleton but having fluorinated and fluorinefree aromatic side-chain substituents. Ternary OPVs having varied ratios of the two SMDs with PC61BM as the acceptor exhibit tunable open-circuit voltages (Vocs) between 0.833 and 0.944 V due to a fluorination-induced shift in energy levels and the electronic “alloy” formed from the miscibility of the two SMDs. A 15% increase in PCE is observed at the optimal ternary SMD ratio, with the short-circuit current density (Jsc) significantly increased to 9.18 mA/cm2. The origin of Jsc enhancement is analyzed via charge generation, transport, and diffuse reflectance measurements, and is attributed to increased optical absorption arising from a maximum in film crystallinity at this SMD ratio, observed by grazing incidence wide-angle X-ray scattering.

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