LaRbp38: A Leishmania amazonensis protein that binds nuclear and kinetoplast DNAs

International Nuclear Information System (INIS)

Lira, C.B.B.; Siqueira Neto, J.L.; Giardini, M.A.; Winck, F.V.; Ramos, C.H.I.; Cano, M.I.N.

2007-01-01

Leishmania amazonensis causes a wide spectrum of leishmaniasis. There are no vaccines or adequate treatment for leishmaniasis, therefore there is considerable interest in the identification of new targets for anti-leishmania drugs. The central role of telomere-binding proteins in cell maintenance makes these proteins potential targets for new drugs. In this work, we used a combination of purification chromatographies to screen L. amazonensis proteins for molecules capable of binding double-stranded telomeric DNA. This approach resulted in the purification of a 38 kDa polypeptide that was identified by mass spectrometry as Rbp38, a trypanosomatid protein previously shown to stabilize mitochondrial RNA and to associate with nuclear and kinetoplast DNAs. Western blotting and supershift assays confirmed the identity of the protein as LaRbp38. Competition and chromatin immunoprecipitation assays confirmed that LaRbp38 interacted with kinetoplast and nuclear DNAs in vivo and suggested that LaRbp38 may have dual cellular localization and more than one function

A Polypyrimidine Tract Binding Protein, Pumpkin RBP50, Forms the Basis of a Phloem-Mobile Ribonucleoprotein Complex[W

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Ham, Byung-Kook; Brandom, Jeri L.; Xoconostle-Cázares, Beatriz; Ringgold, Vanessa; Lough, Tony J.; Lucas, William J.

2009-01-01

RNA binding proteins (RBPs) are integral components of ribonucleoprotein (RNP) complexes and play a central role in RNA processing. In plants, some RBPs function in a non-cell-autonomous manner. The angiosperm phloem translocation stream contains a unique population of RBPs, but little is known regarding the nature of the proteins and mRNA species that constitute phloem-mobile RNP complexes. Here, we identified and characterized a 50-kD pumpkin (Cucurbita maxima cv Big Max) phloem RNA binding protein (RBP50) that is evolutionarily related to animal polypyrimidine tract binding proteins. In situ hybridization studies indicated a high level of RBP50 transcripts in companion cells, while immunolocalization experiments detected RBP50 in both companion cells and sieve elements. A comparison of the levels of RBP50 present in vascular bundles and phloem sap indicated that this protein is highly enriched in the phloem sap. Heterografting experiments confirmed that RBP50 is translocated from source to sink tissues. Collectively, these findings established that RBP50 functions as a non-cell-autonomous RBP. Protein overlay, coimmunoprecipitation, and cross-linking experiments identified the phloem proteins and mRNA species that constitute RBP50-based RNP complexes. Gel mobility-shift assays demonstrated that specificity, with respect to the bound mRNA, is established by the polypyrimidine tract binding motifs within such transcripts. We present a model for RBP50-based RNP complexes within the pumpkin phloem translocation stream. PMID:19122103

CmRBP50 protein phosphorylation is essential for assembly of a stable phloem-mobile high-affinity ribonucleoprotein complex.

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Li, Pingfang; Ham, Byung-Kook; Lucas, William J

2011-07-01

RNA-binding proteins (RBPs) form ribonucleoprotein (RNP) complexes that play crucial roles in RNA processing for gene regulation. The angiosperm sieve tube system contains a unique population of transcripts, some of which function as long-distance signaling agents involved in regulating organ development. These phloem-mobile mRNAs are translocated as RNP complexes. One such complex is based on a phloem RBP named Cucurbita maxima RNA-binding protein 50 (CmRBP50), a member of the polypyrimidine track binding protein family. The core of this RNP complex contains six additional phloem proteins. Here, requirements for assembly of this CmRBP50 RNP complex are reported. Phosphorylation sites on CmRBP50 were mapped, and then coimmunoprecipitation and protein overlay studies established that the phosphoserine residues, located at the C terminus of CmRBP50, are critical for RNP complex assembly. In vitro pull-down experiments revealed that three phloem proteins, C. maxima phloem protein 16, C. maxima GTP-binding protein, and C. maxima phosphoinositide-specific phospholipase-like protein, bind directly with CmRBP50. This interaction required CmRBP50 phosphorylation. Gel mobility-shift assays demonstrated that assembly of the CmRBP50-based protein complex results in a system having enhanced binding affinity for phloem-mobile mRNAs carrying polypyrimidine track binding motifs. This property would be essential for effective long-distance translocation of bound mRNA to the target tissues.

Biotin deficiency enhances the inflammatory response of human dendritic cells.

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Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

2016-09-01

The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

The cyst nematode SPRYSEC protein RBP-1 elicits Gpa2- and RanGAP2-dependent plant cell death.

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Melanie Ann Sacco

2009-08-01

Full Text Available Plant NB-LRR proteins confer robust protection against microbes and metazoan parasites by recognizing pathogen-derived avirulence (Avr proteins that are delivered to the host cytoplasm. Microbial Avr proteins usually function as virulence factors in compatible interactions; however, little is known about the types of metazoan proteins recognized by NB-LRR proteins and their relationship with virulence. In this report, we demonstrate that the secreted protein RBP-1 from the potato cyst nematode Globodera pallida elicits defense responses, including cell death typical of a hypersensitive response (HR, through the NB-LRR protein Gpa2. Gp-Rbp-1 variants from G. pallida populations both virulent and avirulent to Gpa2 demonstrated a high degree of polymorphism, with positive selection detected at numerous sites. All Gp-RBP-1 protein variants from an avirulent population were recognized by Gpa2, whereas virulent populations possessed Gp-RBP-1 protein variants both recognized and non-recognized by Gpa2. Recognition of Gp-RBP-1 by Gpa2 correlated to a single amino acid polymorphism at position 187 in the Gp-RBP-1 SPRY domain. Gp-RBP-1 expressed from Potato virus X elicited Gpa2-mediated defenses that required Ran GTPase-activating protein 2 (RanGAP2, a protein known to interact with the Gpa2 N terminus. Tethering RanGAP2 and Gp-RBP-1 variants via fusion proteins resulted in an enhancement of Gpa2-mediated responses. However, activation of Gpa2 was still dependent on the recognition specificity conferred by amino acid 187 and the Gpa2 LRR domain. These results suggest a two-tiered process wherein RanGAP2 mediates an initial interaction with pathogen-delivered Gp-RBP-1 proteins but where the Gpa2 LRR determines which of these interactions will be productive.

Effects of transcranial direct current stimulation (tDCS) on binge eating disorder.

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Burgess, Emilee E; Sylvester, Maria D; Morse, Kathryn E; Amthor, Frank R; Mrug, Sylvie; Lokken, Kristine L; Osborn, Mary K; Soleymani, Taraneh; Boggiano, Mary M

2016-10-01

To investigate the effect of transcranial direct current stimulation (tDCS) on food craving, intake, binge eating desire, and binge eating frequency in individuals with binge eating disorder (BED). N = 30 adults with BED or subthreshold BED received a 20-min 2 milliampere (mA) session of tDCS targeting the dorsolateral prefrontal cortex (DLPFC; anode right/cathode left) and a sham session. Food image ratings assessed food craving, a laboratory eating test assessed food intake, and an electronic diary recorded binge variables. tDCS versus sham decreased craving for sweets, savory proteins, and an all-foods category, with strongest reductions in men (p tDCS also decreased total and preferred food intake by 11 and 17.5%, regardless of sex (p tDCS administration (p tDCS in BED. Stimulation of the right DLPFC suggests that enhanced cognitive control and/or decreased need for reward may be possible functional mechanisms. The results support investigation of repeated tDCS as a safe and noninvasive treatment adjunct for BED. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:930-936). © 2016 Wiley Periodicals, Inc.

RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice.

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Schouwey, K; Aydin, I T; Radtke, F; Beermann, F

2011-01-20

The Notch signaling pathway is an ubiquitous cell-cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-Jκ-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/° transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-Jκ, as it is rescued in mice lacking RBP-Jκ in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-Jκ. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells.

Gold nanoparticle immunochromatographic assay for quantitative detection of urinary RBP

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XU Kuan

2013-04-01

Full Text Available A rapid quantitative detection of urinary RBP was established by using nano-gold immunochromatography (sandwich method and trisodium citrate reduction method and a rapid immunochromatographic test strip was developed. Theimmunochromatographic test strip can quantitatively detect RBP within 15 minutes. The detection limit was 150ng/mL and detection range was from 150 to 5000 ng/mL. There were no cross-reactions with others kidney disease markers,such as urinary albumin (ALB,transferrin protein (TRF,β2-microglobulin (β2-MG,urinary fiber connecting protein (FN,and lysozyme (LZM. The results indicate that it is a quick and simple method with strong specificity,high sensitivity,and wide detection range. The rapid detection method will have extensive clinical applications in the early diagnosis of proximal tubular damage,kidney disease,diabetic nephropathy,and process monitoring.

RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis

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Sheelarani Karunanithi

2017-08-01

Full Text Available The transmembrane protein, STRA6, functions as a vitamin A transporter and a cytokine receptor when activated by vitamin A-bound serum retinol binding protein 4 (RBP4. STRA6 activation transduces a JAK2-STAT3 signaling cascade and promotes tumorigenesis in a xenograft mouse model of colon cancer. We show here that RBP4 and STRA6 expression is associated with poor oncologic prognosis. Downregulating STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. Furthermore, we show that high-fat diet (HFD increases LGR5 expression and promotes tumor growth in a xenograft model independent of obesity. HFD increased STRA6 levels, and downregulation of STRA6 delays and impairs tumor initiation, tumor growth, and expression of stemness markers. Together, these data demonstrate a key role of STRA6 and RBP4 in the maintenance of colon cancer self-renewal and that this pathway is an important link through which consumption of HFD contributes to colon carcinogenesis.

Non-additive effects of RBP4, ESR1 and IGF2 polymorphisms on litter size at different parities in a Chinese-European porcine line

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Alves Estefânia

2010-06-01

Full Text Available Abstract Background The aim of this work was to study the effects on litter size of variants of the porcine genes RBP4, ESR1 and IGF2, currently used in genetic tests for different purposes. Moreover, we investigated a possible effect of the interaction between RBP4-MspI and ESR1-PvuII polymorphisms. The IGF2-intron3-G3072A polymorphism is actually used to select lean growth, but other possible effects of this polymorphism on reproductive traits need to be evaluated. Methods Detection of polymorphisms in the genomic and cDNA sequences of RBP4 gene was carried out. RBP4-MspI and IGF2-intron3-G3072A were genotyped in a hyperprolific Chinese-European line (Tai-Zumu and three new RBP4 polymorphisms were genotyped in different pig breeds. A bivariate animal model was implemented in association analyses considering the number of piglets born alive at early (NBA12 and later parities (NBA3+ as different traits. A joint analysis of RBP4-MspI and ESR1-PvuII was performed to test their possible interaction. In the IGF2 analysis, paternal or maternal imprinting effects were also considered. Results Four different RBP4 haplotypes were detected (TGAC, GGAG, GAAG and GATG in different pig breeds and wild boars. A significant interaction effect between RBP4-MspI and ESR1-PvuII polymorphisms of 0.61 ± 0.29 piglets was detected on NBA3+. The IGF2 analysis revealed a significant increase on NBA3+ of 0.74 ± 0.37 piglets for the paternally inherited allele A. Conclusions All the analyzed pig and wild boar populations shared one of the four detected RBP4 haplotypes. This suggests an ancestral origin of the quoted haplotype. The joint use of RBP4-MspI and ESR1-PvuII polymorphisms could be implemented to select for higher prolificacy in the Tai-Zumu line. In this population, the paternal allele IGF2-intron3-3072A increased litter size from the third parity. The non-additive effects on litter size reported here should be tested before implementation in other pig

Attentional processing in C57BL/6J mice exposed to developmental vitamin D deficiency.

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Lauren R Harms

Full Text Available Epidemiological evidence suggests that Developmental Vitamin D (DVD deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT and five-choice continuous performance test (5C-CPT, as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour.

Thermometric sensing of peroxide in organic media. Application to monitor the stability of RBP-retinol-HRP complex.

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Ramanathan, K; Jönsson, B R; Danielsson, B

2000-08-01

The stability of horseradish peroxidase (HRP) in aqueous and organic solvents is applied to develop a simple thermometric procedure to detect the binding of retinoic acid-HRP conjugate to retinol binding protein (RBP). Butanone peroxide (BP) in organic phase and hydrogen peroxide in aqueous phase is detected thermometrically on a HRP column, immobilized by cross-linking with glutaraldehyde on controlled pore glass (CPG). Acetone, acetonitrile, methanol, and 2-butanol are used for detection of BP, in the flow injection analysis (FIA) mode. A linear range between 1 and 50 mM BP is obtained in all the organic solvents with a precision of 5-7% (CV%). The magnitude and nature of the thermometric response is significantly different in each organic solvent. The stability of HRP in the organic phase is used to study the stability of a retinoic acid-HRP conjugate bound to immobilized RBP. The response of HRP (to 20 mM BP) in the retinoic acid-HRP conjugate is used as an indicator of the stability of the RBP-retinoic acid-HRP complex, after challenges with various organic/aqueous solvents. Both immobilized HRP and RBP are stable at least for 6 months. The effect of o-phenylene diamine on the thermometric response of HRP is also investigated. A scheme for the design of a thermometric retinol (vitamin A) biosensor is proposed.

Expression of Toll-Like Receptor 2 by Dendritic Cells Is Essential for the DnaJ-ΔA146Ply-Mediated Th1 Immune Response against Streptococcus pneumoniae.

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Wang, Xiaofang; Yuan, Taixian; Yuan, Jun; Su, Yufeng; Sun, Xiaoyu; Wu, Jingwen; Zhang, Hong; Min, Xun; Zhang, Xuemei; Yin, Yibing

2018-03-01

The fusion protein DnaJ-ΔA146Ply could induce cross-protective immunity against pneumococcal infection via mucosal and subcutaneous immunization in mice in the absence of additional adjuvants. DnaJ and Ply are both Toll-like receptor 4 (TLR4) but not TLR2 ligands. However, we found that TLR2 -/- mice immunized subcutaneously with DnaJ-ΔA146Ply showed significantly lower survival rates and higher bacterial loads in nasal washes than did wild-type (WT) mice after being challenged with pneumococcal strain D39 or 19F. The gamma interferon (IFN-γ) level in splenocytes decreased in TLR2 -/- mice, indicating that Th1 immunity elicited by DnaJ-ΔA146Ply was impaired in these mice. We explored the mechanism of protective immunity conferred by DnaJ-ΔA146Ply and the role of TLR2 in this process. DnaJ-ΔA146Ply effectively promoted dendritic cell (DC) maturation via TLR4 but not the TLR2 signaling pathway. In a DnaJ-ΔA146Ply-treated DC and naive CD4 + T cell coculture system, the deficiency of TLR2 in DCs resulted in a significant decline of IFN-γ production and Th1 subset differentiation. The same effect was observed in adoptive-transfer experiments. In addition, TLR2 -/- DCs showed remarkably lower levels of the Th1-polarizing cytokine IL-12p70 than did WT DCs, suggesting that TLR2 was indispensable for DnaJ-ΔA146Ply-induced IL-12 production and Th1 proliferation. Thus, our findings illustrate that dendritic cell expression of TLR2 is essential for optimal Th1 immune response against pneumococci in mice immunized subcutaneously with DnaJ-ΔA146Ply. Copyright © 2018 American Society for Microbiology.

Inhibitory effect of immature dendritic cells (iDCs phagocytizing apoptotic lymphocytes on LPS-mediated activation of iDCs

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Yu-xiang WEI

2013-09-01

Full Text Available Objective　To investigate the inhibitory effect of immature dendritic cells(iDCs on LPS-mediated maturation of iDCs phagocytizing allogeneic spleen lymphocytes after being treated bypsoralen plus ultraviolet A(PUVA. Methods　Bone marrow-derived DCs were obtained from bone marrow cells of C57BL/6 mice by co-cultivation with recombinant mouse IL-4 and GM-CSF. Spleenlymphocytes(SLP of BALB/c mice were isolated and transformed to PUVA-SLP by treatment with 8-methoxy PUVA irradiation.The bone marrow-derived iDCs of C57BL/6 were co-cultured with PUVA-SLP of BALB/c mice to obtain PUVA¬SLPDCs. After incubation, iDCs and PUVA-SP DCs were induced to maturation by LPS(10ng/ml,24h, and then they were analyzed by flow cytometry.At the same time,the concentrations of the immunoreactive proteins IL-12p70,IL-12p40andIL-10 in cell supernatants were determined by ELISA kits according to the manufacturer's recommendations. Results　PUVA-SLP DCs and iDCs were compared in terms of LPS responsiveness.The phenotype of iDCs(CD40,CD80, andCD86 was 50.58%, 66.29%, 71.20%, respectively, showed more rapid changes from immature to mature statein response to LPS stimulation compared with PUVA-SP DCs, the phenotype of which was 21.26%,38.50% and 39.78%, respectively(P0.05.PUVA-SPDCs secreted high levels of IL-10(435.6±13.9, but lowlevels of IL-12(p7018.56±1.3,p4015.22±1.2, as compared with those of iDCs (132.6±2.8, p70192.1±5.9, p40999.8±26.9, P<0.01 after LPS stimulation. Conclusions　Although PUVA-SLPDCs do not express as immature phenotype, they can be readily induced to differentiate into mature DCs in the presence of antigen or LPS. It may be suitable to use iDCs clinically in autoimmune diseases and transplantation.

EEG Driven tDCS Versus Bifrontal tDCS for Tinnitus

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De Ridder, Dirk; Vanneste, Sven

2012-01-01

Tinnitus is the perception of a sound in the absence of any objective physical sound source. Transcranial Direct Current Stimulation (tDCS) induces shifts in membrane resting potentials depending on the polarity of the stimulation: under the anode gamma band activity increases, whereas under the cathode the opposite occurs. Both single and multiple sessions of tDCS over the dorsolateral prefrontal cortex (DLPFC; anode over right DLPFC) yield a transient improvement in tinnitus intensity and t...

Basic science of tDCS

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Michael A. Nitsche

2014-04-01

Full Text Available Neuroplasticity, and functional connectivity are important physiological derivates of cognition, and behaviour. Recently introduced non-invasive brain stimulation techniques are suited to induce, and modulate respective physiological alterations. One of these techniques is transcranial direct current stimulation (tDCS. Its primary mechanism of action is a polarity-dependent subthreshold shift of resting membrane potentials, the after-effects of stimulation depend on the glutamatergic system. Beyond these regional effects, tDCS has been shown recently to alter cortical, as well as cortico-subcortical functional network connectivity. This talk will give an overview about the physiological effects of tDCS, including animal data, and will cover functional consequences of tDCS. Furthermore, new developments with regard to optimization strategies, and the complex interaction of physiological and cognitive processes, will be presented and it will be discussed how tDCS relates to other non-invasive brain stimulation techniques, like transcranial magnetic stimulation (TMS, transcranial alternating current stimulation (tACS, and paired associative stimulation (PAS.

Working memory capacity differentially influences responses to tDCS and HD-tDCS in a retro-cue task.

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Gözenman, Filiz; Berryhill, Marian E

2016-08-26

There is growing interest in non-invasive brain stimulation techniques. A drawback is that the relationship between stimulation and cognitive outcomes for various tasks are unknown. Transcranial direct current stimulation (tDCS) provides diffuse current spread, whereas high-definition tDCS (HD-tDCS) provides more targeted current. The direction of behavioral effects after tDCS can be difficult to predict in cognitive realms such as attention and working memory (WM). Previously, we showed that in low and high WM capacity groups tDCS modulates performance in nearly equal and opposite directions on a change detection task, with improvement for the high capacity participants alone. Here, we used the retro-cue paradigm to test attentional shifting among items in WM to investigate whether WM capacity (WMC) predicted different behavioral consequences during anodal tDCS or HD-tDCS to posterior parietal cortex (PPC). In two experiments, with 24 participants each, we used different stimulus categories (colored circles, letters) and stimulation sites (right, left PPC). The results showed a significant (Experiment 1) or trending (Experiment 2) WMC x stimulation interaction. Compared to tDCS, after HD-tDCS the retro-cueing benefit was significantly greater for the low WMC group but numerically worse for the high WMC group. These data highlight the importance of considering group differences when using non-invasive neurostimulation techniques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The closely related CD103+ dendritic cells (DCs and lymphoid-resident CD8+ DCs differ in their inflammatory functions.

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Zhijun Jiao

Full Text Available Migratory CD103+ and lymphoid-resident CD8+ dendritic cells (DCs share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+ DCs. This superior capacity to drive Th17 responses was also evident in CD103+ DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103+ DCs compared with CD8+ DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103+ DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103+ DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs.

Transcutaneous Spinal Direct Current Stimulation (tsDCS

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Filippo eCogiamanian

2012-07-01

Full Text Available In the past ten years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability (brain polarization or transcranial direct current stimulation, tDCS. Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation.Aiming at developing a new, non invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS on somatosensory potentials (SEPs evoked in healthy subjects by posterior tibial nerve (PTN stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30 without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials, tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic and segmental motor systems.Here we review currently available experimental evidence that non-invasive spinal cord stimulation influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive spinal cord stimulation in managing various pathologic conditions, including pain.

Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural prey Veng, Cambodia.

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Karakochuk, Crystal D; Whitfield, Kyly C; Barr, Susan I; Lamers, Yvonne; Devlin, Angela M; Vercauteren, Suzanne M; Kroeun, Hou; Talukder, Aminuzzaman; McLean, Judy; Green, Timothy J

2015-01-01

Anemia is common in Cambodian women. Potential causes include micronutrient deficiencies, genetic hemoglobin disorders, inflammation, and disease. We aimed to investigate factors associated with anemia (low hemoglobin concentration) in rural Cambodian women (18-45 y) and to investigate the relations between hemoglobin disorders and other iron biomarkers. Blood samples were obtained from 450 women. A complete blood count was conducted, and serum and plasma were analyzed for ferritin, soluble transferrin receptor (sTfR), folate, vitamin B-12, retinol binding protein (RBP), C-reactive protein (CRP), and α1 acid glycoprotein (AGP). Hemoglobin electrophoresis and multiplex polymerase chain reaction were used to determine the prevalence and type of genetic hemoglobin disorders. Overall, 54% of women had a genetic hemoglobin disorder, which included 25 different genotypes (most commonly, hemoglobin E variants and α(3.7)-thalassemia). Of the 420 nonpregnant women, 29.5% had anemia (hemoglobin 8.3 mg/L), hemoglobin disorders, respectively. There was no biochemical evidence of vitamin A deficiency (RBP 5 mg/L) and 26% (AGP >1 g/L) of nonpregnant women, respectively. By using an adjusted linear regression model, the strongest predictors of hemoglobin concentration were hemoglobin E homozygous disorder and pregnancy status. Other predictors were 2 other heterozygous traits (hemoglobin E and Constant Spring), parity, RBP, log ferritin, and vitamin B-12. Multiple biomarkers for anemia and iron deficiency were significantly influenced by the presence of hemoglobin disorders, hence reducing their diagnostic sensitivity. Further investigation of the unexpectedly low prevalence of IDA in Cambodian women is warranted. © 2015 American Society for Nutrition.

Epstein-Barr virus nuclear protein 3C binds to the N-terminal (NTD) and beta trefoil domains (BTD) of RBP/CSL; Only the NTD interaction is essential for lymphoblastoid cell growth

International Nuclear Information System (INIS)

Calderwood, Michael A.; Lee, Sungwook; Holthaus, Amy M.; Blacklow, Stephen C.; Kieff, Elliott; Johannsen, Eric

2011-01-01

Association of EBV nuclear proteins EBNA2, EBNA3A and EBNA3C with RBP/CSL, is essential for lymphoblastoid cell line (LCL) proliferation. Conserved residues in the EBNA3 homology domain, required for RBP/CSL interaction, lack the WΦP motif that mediates EBNA2 and Notch binding to the RBP/CSL beta-trefoil domain (BTD). We map RBP/CSL interacting residues within EBNA3A(aa128-204) and EBNA3C(aa211-233). The EBNA3A results are consistent with an earlier report (aa125-222), but the EBNA3C domain is unexpectedly small and includes a 'WTP' sequence. This EBNA3C WTP motif confers RBP/CSL binding in vitro, in yeast, and in mammalian cells. Further, an EBNA3C WTP → STP(W227S) mutation impaired BTD binding whereas EBNA3 homology domain mutations disrupted RBP/CSL N-terminal domain (NTD) binding. WTP was not essential for EBNA3C repression of EBNA2 in reporter assays or for maintenance of LCL growth. Our results indicate that EBNA3 proteins interact with multiple RBP/CSL domains, but only NTD interactions are required for LCL growth.

Is Motor Learning Mediated by tDCS Intensity?

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Cuypers, Koen; Leenus, Daphnie J. F.; van den Berg, Femke E.; Nitsche, Michael A.; Thijs, Herbert; Wenderoth, Nicole; Meesen, Raf L. J.

2013-01-01

Although tDCS has been shown to improve motor learning, previous studies reported rather small effects. Since physiological effects of tDCS depend on intensity, the present study evaluated this parameter in order to enhance the effect of tDCS on skill acquisition. The effect of different stimulation intensities of anodal tDCS (atDCS) was investigated in a double blind, sham controlled crossover design. In each condition, thirteen healthy subjects were instructed to perform a unimanual motor (...

ATLAS DAQ/HLT rack DCS

International Nuclear Information System (INIS)

Ermoline, Yuri; Burckhart, Helfried; Francis, David; Wickens, Frederick J.

2007-01-01

The ATLAS Detector Control System (DCS) group provides a set of standard tools, used by subsystems to implement their local control systems. The ATLAS Data Acquisition and High Level Trigger (DAQ/HLT) rack DCS provides monitoring of the environmental parameters (air temperatures, humidity, etc.). The DAQ/HLT racks are located in the underground counting room (20 racks) and in the surface building (100 racks). The rack DCS is based on standard ATLAS tools and integrated into overall operation of the experiment. The implementation is based on the commercial control package and additional components, developed by CERN Joint Controls Project Framework. The prototype implementation and measurements are presented

Project managing your simulator DCS upgrade

International Nuclear Information System (INIS)

Carr, S.

2006-01-01

The intention of this paper is to provide helpful information and tips for the purchaser with regard to the project management of a DCS upgrade for an existing nuclear power station operator-training simulator. This paper was written shortly after STS Powergen completed two nuclear power station simulator DCS projects in the USA. Areas covered by this paper are: - Contractual documents and arrangements; - Licence and Escrow agreements; - Liquidated damages; - Project management; - Project schedules and resources; - Monitoring progress; - Defect reporting; - DCS automation code; - Access to proprietary information; - Tips for project meetings; - Testing; - Cultural issues; - Training

Technical Support for the development of DCS

International Nuclear Information System (INIS)

Oh, In Seok; Lee, Cheol Kwon; Kim, Dong Hoon; Kim, Jung Taek; Hwang, In Koo; Park, Jae Chang; Lee, Dong Young; Park, Won Man

2008-05-01

The objective of this project is to provide a technical support to Woori Tech Co. in its design and manufacture process of the DCS as a part of KNICS development program to promote the technology self-reliance for non-safety equipment for NPPs(Nuclear Power Plants). We support Woori Tech Co. to develop a DCS which satisfies the requirements for Shinkori 3 and 4 NPPs in the aspects of reliability, applicability and technical competitiveness. As the results of this project the following items were developed and/or implemented; · Design basis and requirements for a DCS system · Design requirements for control communication networks · Architecture of control networks · Design requirements of EWS(Engineering Workstation) · Plan of software verification and validation · Operation display design · Soft control functions · Application development tools of DCS · Analysis and V/V activities on DCS control network protocols · Software verification and validation and documentation guidelines · User manual documents

Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats (Order: Chiroptera.

Directory of Open Access Journals (Sweden)

Bin Shen

Full Text Available A trade-off between the sensory modalities of vision and hearing is likely to have occurred in echolocating bats as the sophisticated mechanism of laryngeal echolocation requires considerable neural processing and has reduced the reliance of echolocating bats on vision for perceiving the environment. If such a trade-off exists, it is reasonable to hypothesize that some genes involved in visual function may have undergone relaxed selection or even functional loss in echolocating bats. The Gap junction protein, alpha 10 (Gja10, encoded by Gja10 gene is expressed abundantly in mammal retinal horizontal cells and plays an important role in horizontal cell coupling. The interphotoreceptor retinoid-binding protein (Irbp, encoded by the Rbp3 gene is mainly expressed in interphotoreceptor matrix and is known to be critical for normal functioning of the visual cycle. We sequenced Gja10 and Rbp3 genes in a taxonomically wide range of bats with divergent auditory characteristics (35 and 18 species for Gja10 and Rbp3, respectively. Both genes have became pseudogenes in species from the families Hipposideridae and Rhinolophidae that emit constant frequency echolocation calls with Doppler shift compensation at high-duty-cycles (the most sophisticated form of biosonar known, and in some bat species that emit echolocation calls at low-duty-cycles. Our study thus provides further evidence for the hypothesis that a trade-off occurs at the genetic level between vision and echolocation in bats.

Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats (Order: Chiroptera).

Science.gov (United States)

Shen, Bin; Fang, Tao; Dai, Mengyao; Jones, Gareth; Zhang, Shuyi

2013-01-01

A trade-off between the sensory modalities of vision and hearing is likely to have occurred in echolocating bats as the sophisticated mechanism of laryngeal echolocation requires considerable neural processing and has reduced the reliance of echolocating bats on vision for perceiving the environment. If such a trade-off exists, it is reasonable to hypothesize that some genes involved in visual function may have undergone relaxed selection or even functional loss in echolocating bats. The Gap junction protein, alpha 10 (Gja10, encoded by Gja10 gene) is expressed abundantly in mammal retinal horizontal cells and plays an important role in horizontal cell coupling. The interphotoreceptor retinoid-binding protein (Irbp, encoded by the Rbp3 gene) is mainly expressed in interphotoreceptor matrix and is known to be critical for normal functioning of the visual cycle. We sequenced Gja10 and Rbp3 genes in a taxonomically wide range of bats with divergent auditory characteristics (35 and 18 species for Gja10 and Rbp3, respectively). Both genes have became pseudogenes in species from the families Hipposideridae and Rhinolophidae that emit constant frequency echolocation calls with Doppler shift compensation at high-duty-cycles (the most sophisticated form of biosonar known), and in some bat species that emit echolocation calls at low-duty-cycles. Our study thus provides further evidence for the hypothesis that a trade-off occurs at the genetic level between vision and echolocation in bats.

Design of a novel integration-deficient lentivector technology that incorporates genetic and posttranslational elements to target human dendritic cells.

Science.gov (United States)

Tareen, Semih U; Kelley-Clarke, Brenna; Nicolai, Christopher J; Cassiano, Linda A; Nelson, Lisa T; Slough, Megan M; Vin, Chintan D; Odegard, Jared M; Sloan, Derek D; Van Hoeven, Neal; Allen, James M; Dubensky, Thomas W; Robbins, Scott H

2014-03-01

As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted.

DCS emulator development for the ACR-1000 simulator

International Nuclear Information System (INIS)

Nakashima, Y.; Trueman, R.; Ishii, K.

2010-01-01

Nuclear Power Plant (NPP) simulators are the main means for operator training and as such are a crucial part of the NPP operation life-cycle. Hitachi, Ltd., Information and Control Systems Company (henceforth 'Hitachi') is the preferred DCS and DCS emulator developer and supplier for the ACR-1000 NPP control system. Hitachi's concept for the DCS (distributed control system) portion of the ACR-1000 simulator is 'total emulation of the DCS' by software. This paper will review the current status of the technical development and the major project milestones. (author)

Technical Support for the development of DCS

Energy Technology Data Exchange (ETDEWEB)

Oh, In Seok; Lee, Cheol Kwon; Kim, Dong Hoon; Kim, Jung Taek; Hwang, In Koo; Park, Jae Chang; Lee, Dong Young; Park, Won Man

2008-05-15

The objective of this project is to provide a technical support to Woori Tech Co. in its design and manufacture process of the DCS as a part of KNICS development program to promote the technology self-reliance for non-safety equipment for NPPs(Nuclear Power Plants). We support Woori Tech Co. to develop a DCS which satisfies the requirements for Shinkori 3 and 4 NPPs in the aspects of reliability, applicability and technical competitiveness. As the results of this project the following items were developed and/or implemented; {center_dot} Design basis and requirements for a DCS system {center_dot} Design requirements for control communication networks {center_dot} Architecture of control networks {center_dot} Design requirements of EWS(Engineering Workstation) {center_dot} Plan of software verification and validation {center_dot} Operation display design {center_dot} Soft control functions {center_dot} Application development tools of DCS {center_dot} Analysis and V/V activities on DCS control network protocols {center_dot} Software verification and validation and documentation guidelines {center_dot} User manual documents.

Effects of High-Definition and Conventional tDCS on Response Inhibition.

Science.gov (United States)

Hogeveen, J; Grafman, J; Aboseria, M; David, A; Bikson, M; Hauner, K K

2016-01-01

Response inhibition is a critical executive function, enabling the adaptive control of behavior in a changing environment. The inferior frontal cortex (IFC) is considered to be critical for response inhibition, leading researchers to develop transcranial direct current stimulation (tDCS) montages attempting to target the IFC and improve inhibitory performance. However, conventional tDCS montages produce diffuse current through the brain, making it difficult to establish causality between stimulation of any one given brain region and resulting behavioral changes. Recently, high-definition tDCS (HD-tDCS) methods have been developed to target brain regions with increased focality relative to conventional tDCS. Remarkably few studies have utilized HD-tDCS to improve cognitive task performance, however, and no study has directly compared the behavioral effects of HD-tDCS to conventional tDCS. In the present study, participants received either HD-tDCS or conventional tDCS to the IFC during performance of a response inhibition task (stop-signal task, SST) or a control task (choice reaction time task, CRT). A third group of participants completed the same behavioral protocols, but received tDCS to a control site (mid-occipital cortex). Post-stimulation improvement in SST performance was analyzed as a function of tDCS group and the task performed during stimulation using both conventional and Bayesian parameter estimation analyses. Bayesian estimation of the effects of HD- and conventional tDCS to IFC relative to control site stimulation demonstrated enhanced response inhibition for both conditions. No improvements were found after control task (CRT) training in any tDCS condition. Results support the use of both HD- and conventional tDCS to the IFC for improving response inhibition, providing empirical evidence that HD-tDCS can be used to facilitate performance on an executive function task. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance.

Science.gov (United States)

Toloza, F J K; Pérez-Matos, M C; Ricardo-Silgado, M L; Morales-Álvarez, M C; Mantilla-Rivas, J O; Pinzón-Cortés, J A; Pérez-Mayorga, M; Arévalo-García, M L; Tolosa-González, G; Mendivil, C O

2017-09-01

To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

TileDCS web system

International Nuclear Information System (INIS)

Maidantchik, C; Ferreira, F; Grael, F

2010-01-01

The web system described here provides features to monitor the ATLAS Detector Control System (DCS) acquired data. The DCS is responsible for overseeing the coherent and safe operation of the ATLAS experiment hardware. In the context of the Hadronic Tile Calorimeter Detector (TileCal), it controls the power supplies of the readout electronics acquiring voltages, currents, temperatures and coolant pressure measurements. The physics data taking requires the stable operation of the power sources. The TileDCS Web System retrieves automatically data and extracts the statistics for given periods of time. The mean and standard deviation outcomes are stored as XML files and are compared to preset thresholds. Further, a graphical representation of the TileCal cylinders indicates the state of the supply system of each detector drawer. Colors are designated for each kind of state. In this way problems are easier to find and the collaboration members can focus on them. The user selects a module and the system presents detailed information. It is possible to verify the statistics and generate charts of the parameters over the time. The TileDCS Web System also presents information about the power supplies latest status. One wedge is colored green whenever the system is on. Otherwise it is colored red. Furthermore, it is possible to perform customized analysis. It provides search interfaces where the user can set the module, parameters, and the time period of interest. The system also produces the output of the retrieved data as charts, XML files, CSV and ROOT files according to the user's choice.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

Science.gov (United States)

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R

2016-10-15

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcranial direct current stimulation (tDCS) modulation of picture naming and word reading: A meta-analysis of single session tDCS applied to healthy participants.

Science.gov (United States)

Westwood, Samuel J; Romani, Cristina

2017-09-01

Recent reviews quantifying the effects of single sessions of transcranial direct current stimulation (or tDCS) in healthy volunteers find only minor effects on cognition despite the popularity of this technique. Here, we wanted to quantify the effects of tDCS on language production tasks that measure word reading and picture naming. We reviewed 14 papers measuring tDCS effects across a total of 96 conditions to a) quantify effects of conventional stimulation on language regions (i.e., left hemisphere anodal tDCS administered to temporal/frontal areas) under normal conditions or under conditions of cognitive (semantic) interference; b) identify parameters which may moderate the size of the tDCS effect within conventional stimulation protocols (e.g., online vs offline, high vs. low current densities, and short vs. long durations), as well as within types of stimulation not typically explored by previous reviews (i.e., right hemisphere anodal tDCS or left/right hemisphere cathodal tDCS). In all analyses there was no significant effect of tDCS, but we did find a small but significant effect of time and duration of stimulation with stronger effects for offline stimulation and for shorter durations (tDCS and its poor efficacy in healthy participants. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

DCS Budget Tracking System

Data.gov (United States)

Social Security Administration — DCS Budget Tracking System database contains budget information for the Information Technology budget and the 'Other Objects' budget. This data allows for monitoring...

Hits and Misses: Leveraging tDCS to Advance Cognitive Research

Directory of Open Access Journals (Sweden)

Marian E Berryhill

2014-07-01

Full Text Available The popularity of non-invasive brain stimulation techniques in basic, commercial, and applied settings grew tremendously over the last decade. Here, we focus on one popular neurostimulation method: transcranial direct current stimulation (tDCS. Many assumptions regarding the outcomes of tDCS are based on the results of stimulating motor cortex. For instance, the primary motor cortex is predictably suppressed by cathodal tDCS or made more excitable by anodal tDCS. However, wide-ranging studies testing cognition provide more complex and sometimes paradoxical results that challenge this heuristic. Here, we first summarize successful efforts in applying tDCS to cognitive questions, with a focus on working memory. These recent findings indicate that tDCS can result in cognitive task improvement or impairment regardless of stimulation site or direction of current flow. We then report working memory and response inhibition studies that failed to replicate and/or extend previously reported effects. From these opposing outcomes, we present a series of factors to consider that are intended to facilitate future use of tDCS when applied to cognitive questions. In short, common pitfalls include testing too few participants, using insufficiently challenging tasks, using heterogeneous participant populations, and including poorly motivated participants. Furthermore, the poorly understood underlying mechanism for long-lasting tDCS effects make it likely that other important factors predict responses. In conclusion, we argue that although tDCS can be used experimentally to understand brain function its greatest potential may be in applied or translational research.

Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

Directory of Open Access Journals (Sweden)

Doreen Krumbiegel

2005-01-01

Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

TileCal TDAQ/DCS communication

CERN Document Server

Solans, C; Arabidze, G; Carneiro Ferreira, B; Sotto-Maior Peralva, B

2007-01-01

This document describes the communication between the TDAQ and DCS systems of the Hadronic Tile Calorimeter detector of the ATLAS experiment, currently under commissioning phase at CERN. It is a further step on the TDAQ and DCS communication for TileCal operation. The aim of the implementation is to increase the robustness and understanding of the detector from the two systems involved. The basic principle observed is that the two systems operate independently in parallel. Hence, the knowledge of the status of the whole detector from each of the two systems is required for further analysis of the archived data.

Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes

Directory of Open Access Journals (Sweden)

Hoggard N

2012-05-01

Full Text Available Nigel Hoggard1, Abdelali Agouni2, Nimesh Mody2, Mirela Delibegovic21Rowett Institute of Nutrition and Health, 2Integrative Physiology, University of Aberdeen, Aberdeen, UKBackground: Retinol-binding protein 4 (RBP4 is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B expression levels as well as other genes involved in the endoplasmic reticulum (ER stress response are increased in adipose tissue of obese, high-fat-diet-fed mice. In this study we investigated if serum and/or adipose tissue RBP4 protein levels and expression levels of PTP1B and other ER stress-response genes are altered in obese and obese/diabetic men resident in northeast Scotland.Methods: We studied three groups of male volunteers: (1 normal/overweight (body mass index [BMI] < 30, (2 obese (BMI > 30, and (3 obese/diabetic (BMI > 30 controlling their diabetes either by diet or the antidiabetic drug metformin. We analyzed their serum and adipose tissue RBP4 protein levels as well as adipose tissue mRNA expression of PTP1B, binding immunoglobulin protein (BIP, activated transcription factor 4 (ATF4, and glucose-regulated protein 94 (GRP94 alongside other markers of adiposity (percentage body fat, leptin, cholesterol, triglycerides and insulin resistance (oral glucose tolerance tests, insulin, homeostatic model assessment–insulin resistance, C-reactive protein, and adiponectin.Results: We found that obese Scottish subjects had significantly higher serum RBP4 protein levels in comparison to the normal/overweight subjects (P < 0.01. Serum RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (P < 0.05. Adipose tissue RBP4 protein levels were comparable between all three groups of subjects as were serum and adipose transthyretin levels. Adipose tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (P < 0.05; however diet and/or metformin

Longitudinal tDCS: Consistency across Working Memory Training Studies

Directory of Open Access Journals (Sweden)

Marian E. Berryhill

2017-04-01

Full Text Available There is great interest in enhancing and maintaining cognitive function. In recent years, advances in noninvasive brain stimulation devices, such as transcranial direct current stimulation (tDCS, have targeted working memory in particular. Despite controversy surrounding outcomes of single-session studies, a growing field of working memory training studies incorporate multiple sessions of tDCS. It is useful to take stock of these findings because there is a diversity of paradigms employed and the outcomes observed between research groups. This will be important in assessing cognitive training programs paired with stimulation techniques and identifying the more useful and less effective approaches. Here, we treat the tDCS+ working memory training field as a case example, but also survey training benefits in other neuromodulatory techniques (e.g., tRNS, tACS. There are challenges associated with the broad parameter space including: individual differences, stimulation intensity, duration, montage, session number, session spacing, training task selection, timing of follow up testing, near and far transfer tasks. In summary, although the field of assisted cognitive training is young, some design choices are more favorable than others. By way of heuristic, the current evidence supports including more training/tDCS sessions (5+, applying anodal tDCS targeting prefrontal regions, including follow up testing on trained and transfer tasks after a period of no contact. What remains unclear, but important for future translational value is continuing work to pinpoint optimal values for the tDCS parameters on a per cognitive task basis. Importantly the emerging literature shows notable consistency in the application of tDCS for WM across various participant populations compared to single session experimental designs.

DCS data viewer, an application that accesses ATLAS DCS historical data

International Nuclear Information System (INIS)

Tsarouchas, C; Schlenker, S; Dimitrov, G; Jahn, G

2014-01-01

The ATLAS experiment at CERN is one of the four Large Hadron Collider experiments. The Detector Control System (DCS) of ATLAS is responsible for the supervision of the detector equipment, the reading of operational parameters, the propagation of the alarms and the archiving of important operational data in a relational database (DB). DCS Data Viewer (DDV) is an application that provides access to the ATLAS DCS historical data through a web interface. Its design is structured using a client-server architecture. The pythonic server connects to the DB and fetches the data by using optimized SQL requests. It communicates with the outside world, by accepting HTTP requests and it can be used stand alone. The client is an AJAX (Asynchronous JavaScript and XML) interactive web application developed under the Google Web Toolkit (GWT) framework. Its web interface is user friendly, platform and browser independent. The selection of metadata is done via a column-tree view or with a powerful search engine. The final visualization of the data is done using java applets or java script applications as plugins. The default output is a value-over-time chart, but other types of outputs like tables, ascii or ROOT files are supported too. Excessive access or malicious use of the database is prevented by a dedicated protection mechanism, allowing the exposure of the tool to hundreds of inexperienced users. The current configuration of the client and of the outputs can be saved in an XML file. Protection against web security attacks is foreseen and authentication constrains have been taken into account, allowing the exposure of the tool to hundreds of users world wide. Due to its flexible interface and its generic and modular approach, DDV could be easily used for other experiment control systems.

Dcs Data Viewer, an Application that Accesses ATLAS DCS Historical Data

Science.gov (United States)

Tsarouchas, C.; Schlenker, S.; Dimitrov, G.; Jahn, G.

2014-06-01

The ATLAS experiment at CERN is one of the four Large Hadron Collider experiments. The Detector Control System (DCS) of ATLAS is responsible for the supervision of the detector equipment, the reading of operational parameters, the propagation of the alarms and the archiving of important operational data in a relational database (DB). DCS Data Viewer (DDV) is an application that provides access to the ATLAS DCS historical data through a web interface. Its design is structured using a client-server architecture. The pythonic server connects to the DB and fetches the data by using optimized SQL requests. It communicates with the outside world, by accepting HTTP requests and it can be used stand alone. The client is an AJAX (Asynchronous JavaScript and XML) interactive web application developed under the Google Web Toolkit (GWT) framework. Its web interface is user friendly, platform and browser independent. The selection of metadata is done via a column-tree view or with a powerful search engine. The final visualization of the data is done using java applets or java script applications as plugins. The default output is a value-over-time chart, but other types of outputs like tables, ascii or ROOT files are supported too. Excessive access or malicious use of the database is prevented by a dedicated protection mechanism, allowing the exposure of the tool to hundreds of inexperienced users. The current configuration of the client and of the outputs can be saved in an XML file. Protection against web security attacks is foreseen and authentication constrains have been taken into account, allowing the exposure of the tool to hundreds of users world wide. Due to its flexible interface and its generic and modular approach, DDV could be easily used for other experiment control systems.

Communication between Trigger/DAQ and DCS in ATLAS

International Nuclear Information System (INIS)

Burckhart, H.; Jones, R.; Hart, R.; Khomoutnikov, V.; Ryabov, Y.

2001-01-01

Within the ATLAS experiment Trigger/DAQ and DCS are both logically and physically separated. Nevertheless there is a need to communicate. The initial problem definition and analysis suggested three subsystems the Trigger/DAQ DCS Communication (DDC) project should support the ability to: 1. exchange data between Trigger/DAQ and DCS; 2. send alarm messages from DCS to Trigger/DAQ; 3. issue commands to DCS from Trigger/DAQ. Each subsystem is developed and implemented independently using a common software infrastructure. Among the various subsystems of the ATLAS Trigger/DAQ the Online is responsible for the control and configuration. It is the glue connecting the different systems such as data flow, level 1 and high-level triggers. The DDC uses the various Online components as an interface point on the Trigger/DAQ side with the PVSS II SCADA system on the DCS side and addresses issues such as partitioning, time stamps, event numbers, hierarchy, authorization and security. PVSS II is a commercial product chosen by CERN to be the SCADA system for all LHC experiments. Its API provides full access to its database, which is sufficient to implement the 3 subsystems of the DDC software. The DDC project adopted the Online Software Process, which recommends a basic software life-cycle: problem statement, analysis, design, implementation and testing. Each phase results in a corresponding document or in the case of the implementation and testing, a piece of code. Inspection and review take a major role in the Online software process. The DDC documents have been inspected to detect flaws and resulted in a improved quality. A first prototype of the DDC is ready and foreseen to be used at the test-beam during summer 2001

Corticospinal excitability changes to anodal tDCS elucidated with NIRS-EEG joint-imaging

DEFF Research Database (Denmark)

Jindal, Utkarsh; Sood, Mehak; Chowdhury, Shubhajit Roy

2015-01-01

Transcranial direct current stimulation (tDCS) has been shown to modulate corticospinal excitability. We used near-infrared spectroscopy (NIRS) - electroencephalography (EEG) joint-imaging during and after anodal tDCS to measure changes in mean cerebral haemoglobin oxygen saturation (rSO2) along...... with changes in the log-transformed mean-power of EEG within 0.5 Hz - 11.25 Hz. In two separate studies, we investigated local post-tDCS alterations from baseline at the site of anodal tDCS using NIRS-EEG/tDCS joint-imaging as well as local post-tDCS alterations in motor evoked potentials (MEP...... that the innovative technologies for portable NIRS-EEG neuroimaging may be leveraged to objectively quantify the progress (e.g., corticospinal excitability alterations) and dose tDCS intervention as an adjuvant treatment during neurorehabilitation....

The ATLAS Tile Calorimeter DCS for Run 2

CERN Document Server

Pedro Martins, Filipe Manuel; The ATLAS collaboration

2016-01-01

TileCal is one of the ATLAS sub-detectors operating at the Large Hadron Collider (LHC), which is taking data since 2010. The Detector Control System (DCS) was developed to ensure the coherent and safe operation of the whole ATLAS detector. Seventy thousand (70000) parameters are used for control and monitoring purposes of TileCal, requiring an automated system. The TileCal DCS is mainly responsible for the control and monitoring of the high and low voltage systems but it also supervises the detector infrastructure (cooling and racks), calibration systems, data acquisition and safety. During the first period of data taking (Run 1, 2010-12) the TileCal DCS allowed a smooth detector operation and should continue to do so for the second period (Run 2) that started in 2015. The TileCal DCS was updated in order to cope with the hardware and software requirements for Run 2 operation. These updates followed the general ATLAS guidelines on the software and hardware upgrade but also the new requirements from the TileCa...

The ATLAS Tile Calorimeter DCS for Run 2

CERN Document Server

Pedro Martins, Filipe Manuel; The ATLAS collaboration

2016-01-01

TileCal is one of the ATLAS subdetectors operating at the Large Hadron Collider (LHC), which is taking data since 2010. Seventy thousand (70000) parameters are used for control and monitoring purposes, requiring an automated system. The Detector Control System (DCS) was developed to ensure the coherent and safe operation of the whole ATLAS detector. The TileCal DCS is mainly responsible for the control and monitoring of the high and low voltage systems but it also supervises the detector infrastructure (cooling and racks), calibration systems, data acquisition and safety. During the first period of data taking (Run 1, 2010-12) the TileCal DCS allowed a smooth detector operation and should continue to do so for the second period (Run 2) that started in 2015. The TileCal DCS was updated in order to cope with the hardware and software requirements for Run 2 operation. These updates followed the general ATLAS guidelines on the software and hardware upgrade but also the new requirements from the TileCal detector. ...

Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

Science.gov (United States)

Wen, Hui-Zhong; Gao, Shi-Hao; Zhao, Yan-Dong; He, Wen-Juan; Tian, Xue-Long; Ruan, Huai-Zhen

2017-01-01

Background: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia. Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI), we measured pain thresholds before and after anodal-tDCS (A-tDCS) using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models). Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS) and contralateral-tDCS (con-tDCS) produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats. Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical applications. PMID

ATLAS Muon DCS Upgrades and Optimizations

CERN Document Server

Bakalis, Christos; The ATLAS collaboration

2017-01-01

The Muon subsystem is comprised of four detector types: Resistive Plate Chambers (RPC) and Thin Gap Chambers (TGC) for trigger purposes, and Cathode Strip Chambers (CSC) and Muon Drift Tubes (MDT) for muon track reconstruction. The MDTs cover a large area at the outer part of the detector. In total, there are over a 1’000 MDT chambers, which are made of about 350’000 tubes. The luminosity upgrade of the HL-LHC is expected to pose a serious challenge to the MDTs. The expected increase of particle flux will set new, higher standards regarding the operation and control of the chambers. A step towards optimizing the ATLAS Muon Detector Control System (DCS) was to develop several DCS tools, namely a High Luminosity vs Trip Limit panel with its accompanying scripts and managers. The ultimate goal of this tool is to protect the MDT chambers from the rising particle flux and its associated increase in chamber current. In addition to optimizing the ATLAS Muon DCS, several tasks to accommodate the newly installed B...

Cryopreservation of adenovirus-transfected dendritic cells (DCs) for clinical use.

Science.gov (United States)

Gülen, D; Maas, S; Julius, H; Warkentin, P; Britton, H; Younos, I; Senesac, J; Pirruccello, Samuel M; Talmadge, J E

2012-05-01

In this study, we examined the effects of cryoprotectant, freezing and thawing, and adenovirus (Adv) transduction on the viability, transgene expression, phenotype, and function of human dendritic cells (DCs). DCs were differentiated from cultured peripheral blood (PB) monocytes following Elutra isolation using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 6 days and then transduced using an Adv vector with an IL-12 transgene. Fresh, cryopreserved, and thawed transduced immature DCs were examined for their: 1) cellular concentration and viability; 2) antigenicity using an allogeneic mixed lymphocyte reaction (MLR); 3) phenotype (HLA-DR and CD11c) and activation (CD83); and 4) transgene expression based on IL-12 secretion. Stability studies revealed that transduced DCs could be held in cryoprotectant for as long as 75 min at 2-8°C prior to freezing with little effect on their viability and cellularity. Further, cryopreservation, storage, and thawing reduced the viability of the transduced DCs by an average of 7.7%; and had no significant impact on DC phenotype and activation. In summary, cryopreservation, storage, and thawing had no significant effect on DC viability, function, and transgene expression by Adv-transduced DCs. Copyright © 2012 Elsevier B.V. All rights reserved.

Bidirectional interactions between neuronal and hemodynamic responses to transcranial direct current stimulation (tDCS: challenges for brain-state dependent tDCS

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Anirban eDutta

2015-08-01

Full Text Available Transcranial direct current stimulation (tDCS has been shown to modulate cortical neural activity. During neural activity, the electric currents from excitable membranes of brain tissue superimpose in the extracellular medium and generate a potential at scalp, which is referred as the electroencephalogram (EEG. Respective neural activity (energy demand has been shown to be closely related, spatially and temporally, to cerebral blood flow (CBF that supplies glucose (energy supply via neurovascular coupling. The hemodynamic response can be captured by near-infrared spectroscopy (NIRS, which enables continuous monitoring of cerebral oxygenation and blood volume. This neurovascular coupling phenomenon led to the concept of neurovascular unit (NVU that consists of the endothelium, glia, neurons, pericytes, and the basal lamina. Here, recent works suggest NVU as an integrated system working in concert using feedback mechanisms to enable proper brain homeostasis and function where the challenge remains in capturing these mostly nonlinear spatiotemporal interactions within NVU during tDCS. Therefore, we propose EEG-NIRS-based whole-head monitoring of tDCS-induced neuronal and hemodynamic alterations for brain-state dependent tDCS.

Visualizing Transcranial Direct Current Stimulation (tDCS) in vivo using Magnetic Resonance Imaging

Science.gov (United States)

Jog, Mayank Anant

Transcranial Direct Current Stimulation (tDCS) is a low-cost, non-invasive neuromodulation technique that has been shown to treat clinical symptoms as well as improve cognition. However, no techniques exist at the time of research to visualize tDCS currents in vivo. This dissertation presents the theoretical framework and experimental implementations of a novel MRI technique that enables non-invasive visualization of the tDCS electric current using magnetic field mapping. The first chapter establishes the feasibility of measuring magnetic fields induced by tDCS currents. The following chapter discusses the state of the art implementation that can measure magnetic field changes in individual subjects undergoing concurrent tDCS/MRI. The final chapter discusses how the developed technique was integrated with BOLD fMRI-an established MRI technique for measuring brain function. By enabling a concurrent measurement of the tDCS current induced magnetic field as well as the brain's hemodynamic response to tDCS, our technique opens a new avenue to investigate tDCS mechanisms and improve targeting.

Evaluation for nuclear safety-critical software reliability of DCS

International Nuclear Information System (INIS)

Liu Ying

2015-01-01

With the development of control and information technology at NPPs, software reliability is important because software failure is usually considered as one form of common cause failures in Digital I and C Systems (DCS). The reliability analysis of DCS, particularly qualitative and quantitative evaluation on the nuclear safety-critical software reliability belongs to a great challenge. To solve this problem, not only comprehensive evaluation model and stage evaluation models are built in this paper, but also prediction and sensibility analysis are given to the models. It can make besement for evaluating the reliability and safety of DCS. (author)

Surface EEG-Transcranial Direct Current Stimulation (tDCS) Closed-Loop System.

Science.gov (United States)

Leite, Jorge; Morales-Quezada, Leon; Carvalho, Sandra; Thibaut, Aurore; Doruk, Deniz; Chen, Chiun-Fan; Schachter, Steven C; Rotenberg, Alexander; Fregni, Felipe

2017-09-01

Conventional transcranial direct current stimulation (tDCS) protocols rely on applying electrical current at a fixed intensity and duration without using surrogate markers to direct the interventions. This has led to some mixed results; especially because tDCS induced effects may vary depending on the ongoing level of brain activity. Therefore, the objective of this preliminary study was to assess the feasibility of an EEG-triggered tDCS system based on EEG online analysis of its frequency bands. Six healthy volunteers were randomized to participate in a double-blind sham-controlled crossover design to receive a single session of 10[Formula: see text]min 2[Formula: see text]mA cathodal and sham tDCS. tDCS trigger controller was based upon an algorithm designed to detect an increase in the relative beta power of more than 200%, accompanied by a decrease of 50% or more in the relative alpha power, based on baseline EEG recordings. EEG-tDCS closed-loop-system was able to detect the predefined EEG magnitude deviation and successfully triggered the stimulation in all participants. This preliminary study represents a proof-of-concept for the development of an EEG-tDCS closed-loop system in humans. We discuss and review here different methods of closed loop system that can be considered and potential clinical applications of such system.

Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

Directory of Open Access Journals (Sweden)

Hui-Zhong Wen

2017-06-01

Full Text Available Background: Transcranial direct current stimulation (tDCS is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters.Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1 on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia.Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI, we measured pain thresholds before and after anodal-tDCS (A-tDCS using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models.Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS and contralateral-tDCS (con-tDCS produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats.Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical

Understanding public (misunderstanding of tDCS for enhancement

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Laura Yenisa Cabrera

2015-04-01

Full Text Available In order to gain insight into the public’s perspective on using the minimally invasive technique transcranial direct current stimulation (tDCS as an enhancement tool, we analyzed and compared online comments in key popular press articles from two different periods (pre-commercialization and post-commercialization. The main conclusion drawn from this exploratory investigation is that public perception regarding tDCS has shifted from misunderstanding to cautionary realism. This change in attitude can be explained as moving from a focus on an emergent technology to a focus on its applications, benefits, and risks as the technology becomes more grounded within the public domain. Future governance of tDCS should include the concerns and enthusiasms of the public.Keywords: cognitive enhancement, neuroethics, public understanding, transcranial direct current stimulation, brain stimulation, public policy.

Deficiency of RITA results in multiple mitotic defects by affecting microtubule dynamics.

Science.gov (United States)

Steinhäuser, K; Klöble, P; Kreis, N-N; Ritter, A; Friemel, A; Roth, S; Reichel, J M; Michaelis, J; Rieger, M A; Louwen, F; Oswald, F; Yuan, J

2017-04-01

Deregulation of mitotic microtubule (MT) dynamics results in defective spindle assembly and chromosome missegregation, leading further to chromosome instability, a hallmark of tumor cells. RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signaling pathway. Intriguingly, deregulated RITA is involved in primary hepatocellular carcinoma and other malignant entities. We were interested in the potential molecular mechanisms behind its involvement. We show here that RITA binds to tubulin and localizes to various mitotic MT structures. RITA coats MTs and affects their structures in vitro as well as in vivo. Tumor cell lines deficient of RITA display increased acetylated α-tubulin, enhanced MT stability and reduced MT dynamics, accompanied by multiple mitotic defects, including chromosome misalignment and segregation errors. Re-expression of wild-type RITA, but not RITA Δtub ineffectively binding to tubulin, restores the phenotypes, suggesting that the role of RITA in MT modulation is mediated via its interaction with tubulin. Mechanistically, RITA interacts with tubulin/histone deacetylase 6 (HDAC6) and its suppression decreases the binding of the deacetylase HDAC6 to tubulin/MTs. Furthermore, the mitotic defects and increased MT stability are also observed in RITA -/- mouse embryonic fibroblasts. RITA has thus a novel role in modulating MT dynamics and its deregulation results in erroneous chromosome segregation, one of the major reasons for chromosome instability in tumor cells.

Delayed plastic responses to anodal tDCS in older adults

Directory of Open Access Journals (Sweden)

Hakuei eFujiyama

2014-06-01

Full Text Available Despite the abundance of research reporting the neurophysiological and behavioral effects of transcranial direct current stimulation (tDCS in healthy young adults and clinical populations, the extent of potential neuroplastic changes induced by tDCS in healthy older adults is not well understood. The present study compared the extent and time course of anodal tDCS-induced plastic changes in primary motor cortex (M1 in young and older adults. Furthermore, as it has been suggested that neuroplasiticity and associated learning depends on the brain-derived neurotrophic factor (BDNF gene polymorphisms, we also assessed the impact of BDNF polymorphism on these effects. Corticospinal excitability was examined using transcranial magnetic stimulation before and following (0, 10, 20, 30 min anodal tDCS (30 min, 1 mA or sham in young and older adults. While the overall extent of increases in corticospinal excitability induced by anodal tDCS did not vary reliably between young and older adults, older adults exhibited a delayed response; the largest increase in corticospinal excitability occurred 30 min following stimulation for older adults, but immediately post-stimulation for the young group. BDNF genotype did not result in significant differences in the observed excitability increases for either age group. The present study suggests that tDCS-induced plastic changes are delayed as a result of healthy aging, but that the overall efficacy of the plasticity mechanism remains unaffected.

Configuration-defined control algorithms with the ASDEX Upgrade DCS

Energy Technology Data Exchange (ETDEWEB)

Treutterer, Wolfgang, E-mail: Wolfgang.Treutterer@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany); Cole, Richard [Unlimited Computer Systems, Seeshaupter Str. 15, 82393 Iffeldorf Germany (Germany); Gräter, Alexander [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany); Lüddecke, Klaus [Unlimited Computer Systems, Seeshaupter Str. 15, 82393 Iffeldorf Germany (Germany); Neu, Gregor; Rapson, Christopher; Raupp, Gerhard; Zehetbauer, Thomas [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany)

2016-11-15

Highlights: • Control algorithm built from combination of pre-fabricated standard function blocks. • Seamless integration in multi-threaded computation context. • Block composition defined by configuration data, only. - Abstract: The ASDEX Upgrade Discharge Control System (DCS) is a distributed real-time control system executing complex control and monitoring tasks. Up to now, DCS control algorithms have been implemented by coding dedicated application processes with the C++ programming language. Algorithm changes required code modification, compilation and commissioning which only experienced programmers could perform. This was a significant constraint of flexibility for both control system operation and design. The new approach extends DCS with the capability of configuration-defined control algorithms. These are composed of chains of small, configurable standard function blocks providing general purpose functions like algebraic operations, filters, feedback controllers, output limiters and decision logic. In a later phase a graphical editor could help to compose and modify such configuration in a Simulink-like fashion. Building algorithms from standard functions can result in a high number of elements. In order to achieve a similar performance as with C++ coding, it is essential to avoid administrative bottlenecks by design. As a consequence, DCS executes a function block chain in the context of a single real-time thread of an application process. No concurrency issues as in a multi-threaded context need to be considered resulting in strongly simplified signal handling and zero performance overhead for inter-block communication. Instead of signal-driven synchronization, a block scheduler derives the execution sequence automatically from the block dependencies as defined in the configuration. All blocks and connecting signals are instantiated dynamically, based on definitions in a configuration file. Algorithms thus are not defined in the code but only in

Influence of Concurrent Finger Movements on Transcranial Direct Current Stimulation (tDCS)-Induced Aftereffects.

Science.gov (United States)

Shirota, Yuichiro; Terney, Daniella; Antal, Andrea; Paulus, Walter

2017-01-01

Transcranial direct current stimulation (tDCS) has been reported to have bidirectional influence on the amplitude of motor-evoked potentials (MEPs) in resting participants in a polarity-specific manner: anodal tDCS increased and cathodal tDCS decreased them. More recently, the effects of tDCS have been shown to depend on a number of additional factors. We investigated whether a small variety of movements involving target and non-target muscles could differentially modify the efficacy of tDCS. MEPs were elicited from the right first dorsal interosseous muscle, defined as the target muscle, by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). During M1 tDCS, which lasted for 10 min applying anodal, cathodal, or sham condition, the participants were instructed to squeeze a ball with their right hand (Task 1), to move their right index finger only in the medial (Task 2), in the lateral direction (Task 3), or in medial and lateral direction alternatively (Task 4). Anodal tDCS reduced MEP amplitudes measured in Task 1 and Task 2, but to a lesser extent in the latter. In Task 3, anodal tDCS led to greater MEP amplitudes than cathodal stimulation. Alternating movements resulted in no effect of tDCS on MEP amplitude (Task 4). The results are congruent with the current notion that the aftereffects of tDCS are highly variable relying on a number of factors including the type of movements executed during stimulation.

Transcranial Direct Current Stimulation (tDCS): A Promising Treatment for Major Depressive Disorder?

Science.gov (United States)

Bennabi, Djamila; Haffen, Emmanuel

2018-01-01

Background: Transcranial direct current stimulation (tDCS) opens new perspectives in the treatment of major depressive disorder (MDD), because of its ability to modulate cortical excitability and induce long-lasting effects. The aim of this review is to summarize the current status of knowledge regarding tDCS application in MDD. Methods: In this review, we searched for articles published in PubMed/MEDLINE from the earliest available date to February 2018 that explored clinical and cognitive effects of tDCS in MDD. Results: Despite differences in design and stimulation parameters, the examined studies indicated beneficial effects of tDCS for MDD. These preliminary results, the non-invasiveness of tDCS, and its good tolerability support the need for further research on this technique. Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains to be determined. PMID:29734768

New cooling regulation technology of secondary cooling station in DCS

Energy Technology Data Exchange (ETDEWEB)

Zhou, Xuan; Yan, Jun-wei; Zhu, Dong-sheng; Liu, Fei-long; Lei, Jun-xi [The Key Lab of Enhanced Heat Transfer and Energy Conservation of Ministry of Education, School of Chemical and Energy Engineering, South China University of Technology, Guangzhou 510641 (China); Liang, Lie-quan [The Key Lab of E-Commerce Market Application Technology of Guangdong Province, Guangdong University of Business Studies, Guangzhou 510320 (China)

2008-07-01

In this paper, a kind of new control technology of secondary cooling station (constant flow rate/variable temperature difference) in district cooling system (DCS) is proposed in view of serial consequences including low efficiency and high operating cost caused by low temperature of supply water in DCS. This technology has been applied in DCS of Guangzhou University City. The result has already indicated that such technology can increase the supply and return temperatures of buildings, return water temperature of primary side in the plate heat exchanger unit, moreover, the efficiency of both the chiller and the whole system are improved significantly. (author)

Anatomical Parameters of tDCS to Modulate the Motor System after Stroke: A Review

Science.gov (United States)

Lefebvre, Stephanie; Liew, Sook-Lei

2017-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain–behavior connections have rapidly increased in the last 10 years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understand the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement [e.g., neural target(s) and montages employed] may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system. PMID:28232816

Coupling DCS and MARTe: two real-time control frameworks in collaboration

Energy Technology Data Exchange (ETDEWEB)

Rapson, Christopher J., E-mail: chris.rapson@ipp.mpg.de [Max Planck Institute for Plasma Physics, Boltzmannstrasse 2, 85748 Garching (Germany); Carvalho, Pedro [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa (Portugal); Lüddecke, Klaus; Neto, André C. [Unlimited Computer Systems GmbH, Seeshaupterstr. 15, 82393 Iffeldorf (Germany); Santos, Bruno [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa (Portugal); Treutterer, Wolfgang [Max Planck Institute for Plasma Physics, Boltzmannstrasse 2, 85748 Garching (Germany); Winter, Axel [ITER Organization, Route de Vinon-sur-Verdon, 13115 St.-Paul-Lès-Durance (France); Zehetbauer, Thomas [Max Planck Institute for Plasma Physics, Boltzmannstrasse 2, 85748 Garching (Germany)

2014-12-15

Highlights: • Similarities and differences between DCS and MARTe. • Identifies the state-of-the-art in terms of software frameworks for fusion control. • Interfaces developed for realtime and non-realtime communication between DCS and MARTe. • An algorithm replicated in DCS and MARTe produces identical results and good performance. • The start of collaboration to develop a new framework for ITER PCS. - Abstract: Fusion experiments place high demands on real-time control systems. Within the fusion community two modern framework-based software architectures have emerged as powerful tools for developing algorithms for real-time control of complex systems while maintaining the flexibility required when operating a physics experiment. The two frameworks are known as DCS (Discharge Control System), from ASDEX Upgrade and MARTe (Multithreaded Application Real-Time executor), originally from JET. Based on the success of DCS and MARTe, ITER has chosen to develop a framework architecture for its Plasma Control System which will adopt major design concepts from both the existing frameworks. This paper describes a coupling of the two existing frameworks, which was undertaken to explore the degree of similarity and compliance between the concepts, and to extend their capabilities. DCS and MARTe operate in parallel with synchronised state machines and a common message logger. Configuration data is exchanged before the real-time phase. During the real-time phase, structured data is exchanged via shared memory and an existing DCS algorithm is replicated within MARTe. The coupling tests the flexibility and identifies the respective strengths of the two frameworks, providing a well-informed basis on which to move forward and design a new ITER real-time framework.

Coupling DCS and MARTe: two real-time control frameworks in collaboration

International Nuclear Information System (INIS)

Rapson, Christopher J.; Carvalho, Pedro; Lüddecke, Klaus; Neto, André C.; Santos, Bruno; Treutterer, Wolfgang; Winter, Axel; Zehetbauer, Thomas

2014-01-01

Highlights: • Similarities and differences between DCS and MARTe. • Identifies the state-of-the-art in terms of software frameworks for fusion control. • Interfaces developed for realtime and non-realtime communication between DCS and MARTe. • An algorithm replicated in DCS and MARTe produces identical results and good performance. • The start of collaboration to develop a new framework for ITER PCS. - Abstract: Fusion experiments place high demands on real-time control systems. Within the fusion community two modern framework-based software architectures have emerged as powerful tools for developing algorithms for real-time control of complex systems while maintaining the flexibility required when operating a physics experiment. The two frameworks are known as DCS (Discharge Control System), from ASDEX Upgrade and MARTe (Multithreaded Application Real-Time executor), originally from JET. Based on the success of DCS and MARTe, ITER has chosen to develop a framework architecture for its Plasma Control System which will adopt major design concepts from both the existing frameworks. This paper describes a coupling of the two existing frameworks, which was undertaken to explore the degree of similarity and compliance between the concepts, and to extend their capabilities. DCS and MARTe operate in parallel with synchronised state machines and a common message logger. Configuration data is exchanged before the real-time phase. During the real-time phase, structured data is exchanged via shared memory and an existing DCS algorithm is replicated within MARTe. The coupling tests the flexibility and identifies the respective strengths of the two frameworks, providing a well-informed basis on which to move forward and design a new ITER real-time framework

Modulation of selective attention by polarity-specific tDCS effects.

Science.gov (United States)

Pecchinenda, Anna; Ferlazzo, Fabio; Lavidor, Michal

2015-02-01

Selective attention relies on working memory to maintain an attention set of task priorities. Consequently, selective attention is more efficient when working memory resources are not depleted. However, there is some evidence that distractors are processed even when working memory load is low. We used tDCS to assess whether boosting the activity of the Dorsolateral Prefrontal Cortex (DLPFC), involved in selective attention and working memory, would reduce interference from emotional distractors. Findings showed that anodal tDCS over the DLPFC was not sufficient to reduce interference from angry distractors. In contrast, cathodal tDCS over the DLPFC reduced interference from happy distractors. These findings show that altering the DLPFC activity is not sufficient to establish top-down control and increase selective attention efficiency. Although, when the neural signal in the DLPFC is altered by cathodal tDCS, interference from emotional distractors is reduced, leading to an improved performance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using Transcranial Direct Current Stimulation (tDCS to study and treat aphasia

Directory of Open Access Journals (Sweden)

Nazbanou Nozari

2014-04-01

- What are the challenges of using tDCS for hypothesis testing and how can I reduce the risk of misinterpreting my results? In summary, the symposium is designed to (a promote the theoretical understanding of the basic science of tDCS, and (b to tackle several pragmatic issues when designing tDCS studies, with the ultimate goal of cultivating higher standards for using a potentially invaluable technique for both clinical and research purposes. Given the growing interest in the aphasia community for using tDCS and the sophistication of the audience, we believe that the Academy’s annual meeting is the ideal venue for this symposium.

Study on operation I and C DCS test method of EPR project

International Nuclear Information System (INIS)

Meng Ying; Lv Zhihong; Huang Xinnian; Fan Haiying; Li Zhuojia; Xiao Shushu

2014-01-01

Through summarization and optimization of the method for operation I and C DCS test of the European pressurized reactor project, the conclusions play a guiding role on the operation I and C DCS test of the domestic advanced nuclear power plant. The study of the method focuses on the test platform, the test process and the optimization of method of operation I and C DCS test with the practical experience. The reasonable and reliable test method for operation I and C DCS test of the European pressurized reactor project is worthy of the reference and the development in the project of the domestic advanced nuclear power plant. (authors)

Breast cancer instructs dendritic cells to prime interleukin 13–secreting CD4+ T cells that facilitate tumor development

Science.gov (United States)

Aspord, Caroline; Pedroza-Gonzalez, Alexander; Gallegos, Mike; Tindle, Sasha; Burton, Elizabeth C.; Su, Dan; Marches, Florentina; Banchereau, Jacques; Palucka, A. Karolina

2007-01-01

We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417–1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon γ) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid β2 microglobulin–deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development. PMID:17438063

Active suppression of host-vs-graft reaction in pregnant mice. VII. Spontaneous abortion of allogeneic CBA/J x DBA/2 fetuses in the uterus of CBA/J mice correlates with deficient non-T suppressor cell activity

International Nuclear Information System (INIS)

Clark, D.A.; Chaput, A.; Tutton, D.

1986-01-01

The mammalian fetus has been viewed as an unusually successful type of allograft and unexplained spontaneous abortion as a possible example of maternal rejection. Previous studies have shown the presence of small lymphocytic suppressor cells in the murine decidua which block the generation and reactivation of anti-paternal cytotoxic T lymphocytes (CTL) and lymphokine-activated killer cells (LAK) by elaborating a factor that inhibits the response to interleukin 2 (IL 2). A deficiency of these suppressor cells was associated with implants of xenogeneic Mus caroli embryos in the Mus musculus uterus which are infiltrated by maternal lymphoid cells and aborted. A deficiency of such suppressor cells in the lymph nodes draining the uterus of CBA/J females in the process of aborting their semi-allogeneic CBA x DBA/2 F 1 progeny has also been shown. CBA/J females possess significantly lower levels of decidua-associated non-T suppressor cells on day 8.5 to 10.5 of allopregnancy than do mothers that will produce large litters of live babies. The F 1 embryos are infiltrated by maternal lymphocytes prior to abortion, and the infiltration and abortion rate appears to be augmented by pre-immunization with paternal DBA/2 spleen cells. The CBA/J x DBA/2J mating combination provides a model of spontaneous abortion in which immunologic factors play an important role and demonstrates that the association between deficiency of decidua-associated suppressor cells and xenopregnancy failure also holds true for the failure of allopregnancies resulting from natural within-species mating

The Relationship of Fetuin-A, Adiponectin, Retinol Binding Protein-4 (RBP-4 and High Sensitivity C-Reactive Protein (hsCRP with Insulin Resistance (HOMA-IR in Obese Non Diabetic Men

Directory of Open Access Journals (Sweden)

Imelda Novianti

2012-04-01

Full Text Available BACKGROUND: Central obesity is the accumulation of visceral (intra-abdominal fat and is strongly known to be associated with insulin resistance and type 2 diabetes mellitus (T2DM. Obesity can cause adipocyte hypertrophy that results in dysregulation of adipokine expression. The abnormal function of adipocytes may play an important role in the development of a chronic low-grade proinflammatory state associated with obesity. Adiponectin, retinol binding protein (RBP-4 and fetuin-A play a role in the pathophysiology of insulin resistance. Expression of fetuin-A is increased due to fat accumulation in the liver. Elevated concentration of fetuin-A in the circulation can impair insulin signaling in muscle and liver as well as suppress adiponectin secretion, although its molecular mechanism is still unclear. The aim of this study was to identify the relationship of fetuin-A, adiponectin, RBP-4 and hsCRP with insulin resistance in obese non diabetic men. METHODS: This was an observational study with a cross-sectional design. The study subjects were 64 men with non diabetic abdominal obesity, characterized by waist circumference of 98.47±5.88 cm and fasting blood glucose of 85.75±8.36 mg/dL. RESULTS: This study showed that fetuin-A was positively correlated with HOMA-IR in obese non diabetic men with insulin resistance (r=0.128; p=0.570, although not significant. Fetuin-A was found to be correlated with adiponectin, RBP-4 and hsCRP (r=0.150; p=0.233; r=0.050; p=0.711; r=-0.04; p=0.445, although not significant. CONCLUSIONS: The concentration of fetuin-A showed a tendency to be positively correlated with HOMA-IR and with RBP-4 in obese non diabetic men, although statistically not significant. The concentration of fetuin-A showed a tendency to be negatively correlated with adiponectin and hsCRP although statistically not significant. There was no interrelationship between fetuin-A, adiponectin, RBP-4, hsCRP and HOMA-IR. Elevated concentrations of fetuin

CMPK1 and RBP3 are associated with corneal curvature in Asian populations.

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Chen, Peng; Miyake, Masahiro; Fan, Qiao; Liao, Jiemin; Yamashiro, Kenji; Ikram, Mohammad K; Chew, Merywn; Vithana, Eranga N; Khor, Chiea-Chuen; Aung, Tin; Tai, E-Shyong; Wong, Tien-Yin; Teo, Yik-Ying; Yoshimura, Nagahisa; Saw, Seang-Mei; Cheng, Ching-Yu

2014-11-15

Corneal curvature (CC) measures the steepness of the cornea and is an important parameter for clinically diseases such as astigmatism and myopia. Despite the high heritability of CC, only two associated genes have been discovered to date. We performed a three-stage genome-wide association study meta-analysis in 12 660 Asian individuals. Our Stage 1 was done in multiethnic cohorts comprising 7440 individuals, followed by a Stage 2 replication in 2473 Chinese and Stage 3 in 2747 Japanese. The SNP array genotype data were imputed up to the 1000 Genomes Project Phase 1 cosmopolitan panel. The SNP association with the radii of CC was investigated in the linear regression model with the adjustment of age, gender and principal components. In addition to the known genes, MTOR (also known as FRAP1) and PDGFRA, we discovered two novel genes associated with CC: CMPK1 (rs17103186, P = 3.3 × 10(-12)) and RBP3 (rs11204213 [Val884Met], P = 1.1 × 10(-13)). The missense RBP3 SNP, rs11204213, was also associated with axial length (AL) (P = 4.2 × 10(-6)) and had larger effects on both CC and AL compared with other SNPs. The index SNPs at the four indicated loci explained 1.9% of CC variance across the Stages 1 and 2 cohorts, while 33.8% of CC variance was explained by the genome-wide imputation data. We identified two novel genes influencing CC, which are related to either corneal shape or eye size. This study provides additional insights into genetic architecture of corneal shape. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Transcranial Direct Current Stimulation (tDCS) Enhances the Excitability of Trigemino-Facial Reflex Circuits.

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Cabib, Christopher; Cipullo, Federica; Morales, Merche; Valls-Solé, Josep

2016-01-01

Transcranial direct current stimulation (tDCS) causes a tiny burning sensation through activation of local cutaneous trigeminal afferents. Trigeminal sensory inputs from tDCS may generate excitability changes in the trigemino-facial reflex circuits. Sixteen healthy volunteers were submitted to 20 minutes tDCS sessions with two types of electrode-montage conditions: 1. Real vs Sham 'bi-hemispheric' tDCS (cathode/anode: C4/C3), for blinded assessment of effects, and 2. 'uni-hemispheric' tDCS (cathode/anode: Fp3/C3), for assessment of laterality of the effects. Supraorbital nerve stimuli were used to obtain blink reflexes before, during (10 minutes from onset) and after (30 minutes from onset) the tDCS session. Outcome measures were R2 habituation (R2H) to repeated stimuli, the blink reflex excitability recovery (BRER) to paired stimuli and the blink reflex inhibition by a prepulse (BRIP). Real but not sham bi-hemispheric tDCS caused a significant decrease of R2H and leftward shift of BRER curve (p tDCS on BRER and BRIP were larger on ipsilateral than on contralateral blink reflexes (p tDCS enhances the excitability of trigemino-facial reflex circuits. The finding of larger ipsilateral than contralateral effects suggests that sensitization through cutaneous trigeminal afferents adds on other possible mechanisms such as activation of cortico-nuclear or cortico-reticular connections. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of different language and tDCS interventions in PPA and their neural correlates

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Kyrana Tsapkini

2015-05-01

Results: First, we replicated our previous results obtained with fewer participants: all improved in both tDCS and sham conditions on trained items. Generalization of treatment on untrained items was significant only in tDCS condition. Therapy gains lasted longer in tDCS condition as well. Second, preliminary analyses of rs-fMRI show changes of functional connectivity between written language areas in the tDCS and sham conditions. Conclusions: tDCS represents an increasingly valuable treatment option in language rehabilitation even in neurodegeneration. Late intervention is as beneficial as early intervention but improvement seems more dramatic in early cases. Different possibilities are discussed: tDCS may indeed change the course of the disease, i.e., it may slow down the rate of decline or, language improvement due to tDCS (or delay in language deterioration due to the course of the disease may hold the spread of decline in other cognitive functions, thus, early interventions appear more beneficial. The correlation between functional connectivity and language production outcomes is expected to shed light on how tDCS works in the brains of people with a neurodegenerative disease. Implications of functional connectivity changes between language areas involved in the targeted language function will inform further interventions.

Frontoparietal tDCS Benefits Visual Working Memory in Older Adults With Low Working Memory Capacity.

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Arciniega, Hector; Gözenman, Filiz; Jones, Kevin T; Stephens, Jaclyn A; Berryhill, Marian E

2018-01-01

Working memory (WM) permits maintenance of information over brief delays and is an essential executive function. Unfortunately, WM is subject to age-related decline. Some evidence supports the use of transcranial direct current stimulation (tDCS) to improve visual WM. A gap in knowledge is an understanding of the mechanism characterizing these tDCS linked effects. To address this gap, we compared the effects of two tDCS montages designed on visual working memory (VWM) performance. The bifrontal montage was designed to stimulate the heightened bilateral frontal activity observed in aging adults. The unilateral frontoparietal montage was designed to stimulate activation patterns observed in young adults. Participants completed three sessions (bilateral frontal, right frontoparietal, sham) of anodal tDCS (20 min, 2 mA). During stimulation, participants performed a visual long-term memory (LTM) control task and a visual WM task. There was no effect of tDCS on the LTM task. Participants receiving right unilateral tDCS showed a WM benefit. This pattern was most robust in older adults with low WM capacity. To address the concern that the key difference between the two tDCS montages could be tDCS over the posterior parietal cortex (PPC), we included new analyses from a previous study applying tDCS targeting the PPC paired with a recognition VWM task. No significant main effects were found. A subsequent experiment in young adults found no significant effect of either tDCS montage on either task. These data indicate that tDCS montage, age and WM capacity should be considered when designing tDCS protocols. We interpret these findings as suggestive that protocols designed to restore more youthful patterns of brain activity are superior to those that compensate for age-related changes.

Effects of tDCS on Bimanual Motor Skills: A Brief Review.

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Pixa, Nils H; Pollok, Bettina

2018-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that allows the modulation of cortical excitability as well as neuroplastic reorganization using a weak constant current applied through the skull on the cerebral cortex. TDCS has been found to improve motor performance in general and motor learning in particular. However, these effects have been reported almost exclusively for unimanual motor tasks such as serial reaction time tasks, adaptation tasks, or visuo-motor tracking. Despite the importance of bimanual actions in most activities of daily living, only few studies have investigated the effects of tDCS on bimanual motor skills. The objectives of this review article are: (i) to provide a concise overview of the few existing studies in this area; and (ii) to discuss the effects of tDCS on bimanual motor skills in healthy volunteers and patients suffering from neurological diseases. Despite considerable variations in stimulation protocols, the bimanual tasks employed, and study designs, the data suggest that tDCS has the potential to enhance bimanual motor skills. The findings imply that the effects of tDCS vary with task demands, such as complexity and the level of expertise of the participating volunteers. Nevertheless, optimized stimulation protocols tailored to bimanual tasks and individual performance considering the underlying neural substrates of task execution are required in order to probe the effectiveness of tDCS in greater detail, thus creating an opportunity to support motor recovery in neuro-rehabilitation.

Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS)

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Alam, Mahtab; Truong, Dennis Q.; Khadka, Niranjan; Bikson, Marom

2016-06-01

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability—enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm2) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring’s diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation (\

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance.

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Molero-Chamizo, Andrés; Alameda Bailén, José R; Garrido Béjar, Tamara; García López, Macarena; Jaén Rodríguez, Inmaculada; Gutiérrez Lérida, Carolina; Pérez Panal, Silvia; González Ángel, Gloria; Lemus Corchero, Laura; Ruiz Vega, María J; Nitsche, Michael A; Rivera-Urbina, Guadalupe N

2018-02-01

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS-namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.

The Integration of DCS I/O to an Existing PLC

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Sadhukhan, Debashis; Mihevic, John

2013-01-01

At the NASA Glenn Research Center (GRC), Existing Programmable Logic Controller (PLC) I/O was replaced with Distributed Control System (DCS) I/O, while keeping the existing PLC sequence Logic. The reason for integration of the PLC logic and DCS I/O, along with the evaluation of the resulting system is the subject of this paper. The pros and cons of the old system and new upgrade are described, including operator workstation screen update times. Detail of the physical layout and the communication between the PLC, the DCS I/O and the operator workstations are illustrated. The complex characteristics of a central process control system and the plan to remove the PLC processors in future upgrades is also discussed.

Translating tDCS into the field of obesity: mechanism-driven approaches

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Miguel eAlonso-Alonso

2013-08-01

Full Text Available Transcranial direct current stimulation (tDCS is emerging as a promising technique for neuromodulation in a variety of clinical conditions. Recent neuroimaging studies suggest that modifying the activity of brain circuits involved in eating behavior could provide therapeutic benefits in obesity. One session of tDCS over the dorsolateral prefrontal cortex can induce an acute decrease in food craving, according to three small clinical trials, but the extension of these findings into the field of obesity remains unexplored. Importantly, there has been little/no interaction of our current understanding of tDCS and its mechanisms with obesity-related research. How can we start closing this gap and rationally guide the translation of tDCS into the field of obesity? In this mini-review I summarize some of the challenges and questions ahead, related to basic science and technical aspects, and suggest future directions.

Functional connectivity substrates for tDCS response in Minimally Conscious State patients

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Carlo Cavaliere

2016-11-01

Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI of 16 sub-acute and chronic MCS patients (6 tDCS responders who successively received a single left dorsolateral prefrontal cortex (DLPFC tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network and default-mode network was performed.TDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus.Our findings suggest that a prior high connectivity with regions belonging to extrinsic control network can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

Using transcranial direct-current stimulation (tDCS) to understand cognitive processing.

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Reinhart, Robert M G; Cosman, Josh D; Fukuda, Keisuke; Woodman, Geoffrey F

2017-01-01

Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability.

Anodal tDCS to V1 blocks visual perceptual learning consolidation.

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Peters, Megan A K; Thompson, Benjamin; Merabet, Lotfi B; Wu, Allan D; Shams, Ladan

2013-06-01

This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

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Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

2017-01-01

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS

Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

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Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe

2011-01-01

Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126

Clinical predictors of acute response to transcranial direct current stimulation (tDCS) in major depression.

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D'Urso, Giordano; Dell'Osso, Bernardo; Rossi, Rodolfo; Brunoni, Andre Russowsky; Bortolomasi, Marco; Ferrucci, Roberta; Priori, Alberto; de Bartolomeis, Andrea; Altamura, Alfredo Carlo

2017-09-01

Transcranial direct current stimulation (tDCS) is a promising neuromodulation intervention for poor-responding or refractory depressed patients. However, little is known about predictors of response to this therapy. The present study aimed to analyze clinical predictors of response to tDCS in depressed patients. Clinical data from 3 independent tDCS trials on 171 depressed patients (including unipolar and bipolar depression), were pooled and analyzed to assess predictors of response. Depression severity and the underlying clinical dimensions were measured using the Hamilton Depression Rating Scale (HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis (bipolar/unipolar depression) were also investigated as predictors of response. Linear mixed models were fitted in order to ascertain which HDRS factors were associated with response to tDCS. Age, gender and diagnosis did not show any association with response to treatment. The reduction in HDRS scores after tDCS was strongly associated with the baseline values of "Cognitive Disturbances" and "Retardation" factors, whilst the "Anxiety/Somatization" factor showed a mild association with the response. Open-label design, the lack of control group, and minor differences in stimulation protocols. No differences in response to tDCS were found between unipolar and bipolar patients, suggesting that tDCS is effective for both conditions. "Cognitive disturbance", "Retardation", and "Anxiety/Somatization", were identified as potential clinical predictors of response to tDCS. These findings point to the pre-selection of the potential responders to tDCS, therefore optimizing the clinical use of this technique and the overall cost-effectiveness of the psychiatric intervention for depressed patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder.

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Oliveira, Janaina F; Zanão, Tamires A; Valiengo, Leandro; Lotufo, Paulo A; Benseñor, Isabela M; Fregni, Felipe; Brunoni, André R

2013-03-14

Based on previous studies showing that transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that employs weak, direct currents to induce cortical-excitability changes, might be useful for working memory (WM) enhancement in healthy subjects and also in treating depressive symptoms, our aim was to evaluate whether tDCS could acutely enhance WM in depressed patients. Twenty-eight age- and gender-matched, antidepressant-free depressed subjects received a single-session of active/sham tDCS in a randomized, double-blind, parallel design. The anode was positioned over the left and the cathode over the right dorsolateral prefrontal cortex. The n-back task was used for assessing WM and it was performed immediately before and 15min after tDCS onset. We found that active vs. sham tDCS led to an increase in the rate of correct responses. We also used signal detection theory analyses to show that active tDCS increased both discriminability, i.e., the ability to discriminate signal (correct responses) from noise (false alarms), and response criterion, indicating a lower threshold to yield responses. All effect sizes were large. In other words, one session of tDCS acutely enhanced WM in depressed subjects, suggesting that tDCS can improve "cold" (non affective-loaded) working memory processes in MDD. Based on these findings, we discuss the effects of tDCS on WM enhancement in depression. We also suggest that the n-back task could be used as a biomarker in future tDCS studies investigating prefrontal activity in healthy and depressed samples. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Effects of Transcranial Direct Current Stimulation (tDCS on Multitasking Throughput Capacity

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Justin Nelson

2016-11-01

Full Text Available Background: Multitasking has become an integral attribute associated with military operations within the past several decades. As the amount of information that needs to be processed during these high level multitasking environments exceeds the human operators’ capabilities, the information throughput capacity reaches an asymptotic limit. At this point, the human operator can no longer effectively process and respond to the incoming information resulting in a plateau or decline in performance. The objective of the study was to evaluate the efficacy of a non-invasive brain stimulation technique known as transcranial direct current stimulation (tDCS applied to a scalp location over the left dorsolateral prefrontal cortex (lDLPFC to improve information processing capabilities during a multitasking environment. Methods: The study consisted of 20 participants from Wright-Patterson Air Force Base (16 male and 4 female with an average age of 31.1 (SD = 4.5. Participants were randomly assigned into two groups, each consisting of eight males and two females. Group one received 2mA of anodal tDCS and group two received sham tDCS over the lDLPFC on their testing day. Results: The findings indicate that anodal tDCS significantly improves the participants’ information processing capability resulting in improved performance compared to sham tDCS. For example, the multitasking throughput capacity for the sham tDCS group plateaued near 1.0 bits/s at the higher baud input (2.0 bits/s whereas the anodal tDCS group plateaued near 1.3 bits/s. Conclusion: The findings provided new evidence that tDCS has the ability to augment and enhance multitasking capability in a human operator. Future research should be conducted to determine the longevity of the enhancement of transcranial direct current stimulation on multitasking performance, which has yet to be accomplished.

The Effects of Transcranial Direct Current Stimulation (tDCS) on Multitasking Throughput Capacity.

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Nelson, Justin; McKinley, Richard A; Phillips, Chandler; McIntire, Lindsey; Goodyear, Chuck; Kreiner, Aerial; Monforton, Lanie

2016-01-01

Background: Multitasking has become an integral attribute associated with military operations within the past several decades. As the amount of information that needs to be processed during these high level multitasking environments exceeds the human operators' capabilities, the information throughput capacity reaches an asymptotic limit. At this point, the human operator can no longer effectively process and respond to the incoming information resulting in a plateau or decline in performance. The objective of the study was to evaluate the efficacy of a non-invasive brain stimulation technique known as transcranial direct current stimulation (tDCS) applied to a scalp location over the left dorsolateral prefrontal cortex (lDLPFC) to improve information processing capabilities during a multitasking environment. Methods: The study consisted of 20 participants from Wright-Patterson Air Force Base (16 male and 4 female) with an average age of 31.1 (SD = 4.5). Participants were randomly assigned into two groups, each consisting of eight males and two females. Group one received 2 mA of anodal tDCS and group two received sham tDCS over the lDLPFC on their testing day. Results: The findings indicate that anodal tDCS significantly improves the participants' information processing capability resulting in improved performance compared to sham tDCS. For example, the multitasking throughput capacity for the sham tDCS group plateaued near 1.0 bits/s at the higher baud input (2.0 bits/s) whereas the anodal tDCS group plateaued near 1.3 bits/s. Conclusion: The findings provided new evidence that tDCS has the ability to augment and enhance multitasking capability in a human operator. Future research should be conducted to determine the longevity of the enhancement of transcranial direct current stimulation on multitasking performance, which has yet to be accomplished.

Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions

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Jamart Jacques

2010-03-01

Full Text Available Abstract Background Transcranial direct current stimulation (tDCS is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. Its safety profile places tDCS in the pole-position for translating in real-world therapeutic application. However, an episode of transient respiratory depression in a subject receiving tDCS with an extracephalic electrode led to the suggestion that such an electrode montage could modulate the brainstem autonomic centres. We investigated whether tDCS applied over the midline frontal cortex in 30 healthy volunteers (sham n = 10, cathodal n = 10, anodal n = 10 with an extracephalic reference electrode would modulate brainstem activity as reflected by the monitoring and stringent analysis of vital parameters: heart rate (variability, respiratory rate, blood pressure and sympatho-vagal balance. We reasoned that this study could lead to two opposite but equally interesting outcomes: 1 If tDCS with an extracephalic electrode modulated vital parameters, it could be used as a new tool to explore the autonomic nervous system and, even, to modulate its activity for therapeutic purposes. 2 On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could thus be used safely in healthy human subjects. This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. Indeed, on the one hand, using an extracephalic electrode as a genuine neutral reference (as opposed to the classical "bi-cephalic" tDCS montages which deliver bi-polar stimulation of the brain would help to comfort the conclusions of several modern studies regarding the spatial location and polarity of tDCS. On the other hand, using an extracephalic reference electrode may impact differently on a given cortical target due to the change of direct current flow direction; this may enlarge the potential interventions with tDCS. Results Whereas the respiratory

DCS cabinet power loss analysis for CPR1000 nuclear power plant

International Nuclear Information System (INIS)

Zhou Liang; Zhao Yanfeng; Sun Yongbin

2014-01-01

The DCS overall structure of CRP1000 nuclear power plant was introduced. Based on the RPC, the signal interface character and signal processing mechanism on the key root were analyzed. By the power loss analyzing of RPC, the RPC loss power may lead reactor trip signal from anticipated transient without scram (ATWS) system. The results indicate that it is necessary to search DCS cabinet power loss analysis. Optimizing and assigning the main water flow signals can avoid trigger reactor trip signal by mistake. The DCS cabinet power loss analysis can optimize the I and C (instrumentation and control) design and increase the nuclear plant's reliability. (authors)

Anodal tDCS applied during multitasking training leads to transferable performance gains.

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Filmer, Hannah L; Lyons, Maxwell; Mattingley, Jason B; Dux, Paul E

2017-10-11

Cognitive training can lead to performance improvements that are specific to the tasks trained. Recent research has suggested that transcranial direct current stimulation (tDCS) applied during training of a simple response-selection paradigm can broaden performance benefits to an untrained task. Here we assessed the impact of combined tDCS and training on multitasking, stimulus-response mapping specificity, response-inhibition, and spatial attention performance in a cohort of healthy adults. Participants trained over four days with concurrent tDCS - anodal, cathodal, or sham - applied to the left prefrontal cortex. Immediately prior to, 1 day after, and 2 weeks after training, performance was assessed on the trained multitasking paradigm, an untrained multitasking paradigm, a go/no-go inhibition task, and a visual search task. Training combined with anodal tDCS, compared with training plus cathodal or sham stimulation, enhanced performance for the untrained multitasking paradigm and visual search tasks. By contrast, there were no training benefits for the go/no-go task. Our findings demonstrate that anodal tDCS combined with multitasking training can extend to untrained multitasking paradigms as well as spatial attention, but with no extension to the domain of response inhibition.

Effects of HD-tDCS on memory and metamemory for general knowledge questions that vary by difficulty

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Chua, Elizabeth F.; Ahmed, Rifat; Garcia, Sandry

2016-01-01

Background The ability to monitor one’s own memory is an important feature of normal memory and is an aspect of ‘metamemory’. Lesion studies have shown dissociations between memory and metamemory, but only single dissociations have been shown using transcranial direct current stimulation (tDCS). One potential reason that only single dissociations have been shown is that tDCS effects may be moderated by task difficulty. Objective/Hypothesis We used high definition (HD) tDCS to test for dissociable roles of the dorsolateral prefrontal cortex (DLPFC) and anterior temporal lobe (ATL) in semantic long-term memory and metamemory tasks. We also tested whether general knowledge question difficulty moderated the effects of HD-tDCS. Methods Across 3 sessions, participants received active HD-tDCS over the left DLPFC or left ATL, or sham HD-tDCS during general knowledge recall and recognition tests, and a ‘feeling-of-knowing’ metamemory task. General knowledge questions were blocked by difficulty. Repeated measures ANOVAs were used to examine the effects of HD-tDCS on memory and metamemory tasks by memory question difficulty. Results HD-tDCS over the ATL led to improved recall compared to DLPFC and sham HD-tDCS, and this occurred only for medium difficulty questions. In contrast, for non-recalled questions, HD-tDCS over the DLPFC led to improved recognition accuracy and improved feeling-of-knowing accuracy compared to ATL and sham HD-tDCS, and this was not moderated by memory question difficulty. Conclusion(s) HD-tDCS can be used to dissociate the roles of the ATL and DLPFC in different memory and ‘metamemory’ tasks. The effects of HD-tDCS on task may be moderated by task difficulty, depending on the nature of the task and site of stimulation. PMID:27876306

Transcranial direct-current stimulation (tDCS) for bipolar depression: A systematic review and meta-analysis.

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Dondé, Clément; Amad, Ali; Nieto, Isabel; Brunoni, André Russowsky; Neufeld, Nicholas H; Bellivier, Frank; Poulet, Emmanuel; Geoffroy, Pierre-Alexis

2017-08-01

Bipolar disorder (BD) is a severe and recurrent brain disorder that can manifest in manic or depressive episodes. Transcranial Direct Current Stimulation (tDCS) has been proposed as a novel therapeutic modality for patients experiencing bipolar depression, for which standard treatments are often inefficient. While several studies have been conducted in this patient group, there has been no systematic review or meta-analysis that specifically examines bipolar depression. We aimed to address this gap in the literature and evaluated the efficacy and tolerability of tDCS in patients fulfilling DSM-IV-TR criteria for BD I, II, or BD not otherwise specified (NOS). We systematically searched the literature from April 2002 to November 2016 to identify relevant publications for inclusion in our systematic review and meta-analysis. Effect sizes for depression rating-scale scores were expressed as the standardized mean difference (SMD) before and after tDCS. Thirteen of 382 identified studies met eligibility criteria for our systematic review. The meta-analysis included 46 patients from 7 studies with depression rating-scale scores pre- and post-tDCS. Parameters of tDCS procedures were heterogeneous. Depression scores decreased significantly with a medium effect size after acute-phase of treatment (SMD 0.71 [0.25-1.18], z=3.00, p=0.003) and at the furthest endpoint (SMD 1.27 [0.57-1.97], z=3.57, p=0.0004). Six cases of affective switching under tDCS treatment protocols were observed. Depressive symptoms respond to tDCS in patients with BD. Additional studies, and particularly randomized controlled trials, are needed to clarify the effectiveness of tDCS in bipolar depression, the frequency of tDCS-emergent hypomania/mania, and which tDCS modalities are most efficient. Copyright © 2017 Elsevier Inc. All rights reserved.

Xue-fu-Zhu-Yu decoction protects rats against retinal ischemia by downregulation of HIF-1α and VEGF via inhibition of RBP2 and PKM2.

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Tan, Shu-Qiu; Geng, Xue; Liu, Jorn-Hon; Pan, Wynn Hwai-Tzong; Wang, Li-Xiang; Liu, Hui-Kang; Hu, Lei; Chao, Hsiao-Ming

2017-07-14

Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed. Significant ischemic changes occurred after ischemia including decreased ERG b-wave ratios, less numerous retinal ganglion cells (RGCs), reduced inner retinal thickness, fewer choline acetyltransferase (ChAT) labeled amacrine cell bodies, increased glial fibrillary acidic protein (GFAP) immunoreactivity and increased vimentin Müller immunolabeling. These were accompanied by significant increases in the mRNA/protein concentrations of vascular endothelium growth factor, hypoxia-inducible factor-1α, pyruvate kinase M2 and retinoblastoma-binding protein 2. The ischemic changes were concentration-dependently and significantly altered when XFZYD was given for seven consecutive days before or after retina ischemia, compared to vehicle. These alterations included enhanced ERG b-wave amplitudes, more numerous RGCs, enhanced inner retinal thickness, a greater number of ChAT immunolabeled amacrine cell bodies and decreased GFAP/vimentin immunoreactivity. Furthermore, decreased mRNA levels of VEGF, HIF-1α, PKM2, and RBP2 were also found. Reduced protein concentrations of VEGF, HIF-1α, PKM2, and RBP2 were also demonstrated. Furthermore, there was an inhibition of the ischemia-associated increased ratios (target protein/β-actin) in the protein levels of VEGF, HIF-1α, PKM2, and RBP2, which were induced by Shikonin, JIB-04 or Avastin. XFZYD would seem to protect against well-known retinal ischemic changes via a synergistic inhibition of RBP2 and PKM2, as well as down-regulation of HIF-1�

Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia.

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Richardson, Jessica; Datta, Abhishek; Dmochowski, Jacek; Parra, Lucas C; Fridriksson, Julius

2015-01-01

Transcranial direct current stimulation (tDCS) enhances treatment outcomes post-stroke. Feasibility and tolerability of high-definition (HD) tDCS (a technique that increases current focality and intensity) for consecutive weekdays as an adjuvant to behavioral treatment in a clinical population has not been demonstrated. To determine HD-tDCS feasibility outcomes: 1) ability to implement study as designed, 2) acceptability of repeated HD-tDCS administration to patients, and 3) preliminary efficacy. Eight patients with chronic post-stroke aphasia participated in a randomized crossover trial with two arms: conventional sponge-based (CS) tDCS and HD-tDCS. Computerized anomia treatment was administered for five consecutive days during each treatment arm. Individualized modeling/targeting procedures and an 8-channel HD-tDCS device were developed. CS-tDCS and HD-tDCS were comparable in terms of implementation, acceptability, and outcomes. Naming accuracy and response time improved for both stimulation conditions. Change in accuracy of trained items was numerically higher (but not statistically significant) for HD-tDCS compared to CS-tDCS for most patients. Regarding feasibility, HD-tDCS treatment studies can be implemented when designed similarly to documented CS-tDCS studies. HD-tDCS is likely to be acceptable to patients and clinicians. Preliminary efficacy data suggest that HD-tDCS effects, using only 4 electrodes, are at least comparable to CS-tDCS.

Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin-12/interleukin-23-deficient mice

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Bastos, Karina R B; de Deus Vieira de Moraes, Luciana; Zago, Cláudia A; Marinho, Cláudio R F; Russo, Momtchilo; Alvarez, José M M; D'Império Lima, Maria R

2005-01-01

We have previously shown that macrophages from interleukin (IL)-12p40 gene knockout (IL-12/IL-23−/−) mice have a bias towards the M2 activation profile, spontaneously secreting large quantities of transforming growth factor-β1 (TGF-β1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon-γ (IFN-γ). To verify whether the activation profile of dendritic cells (DCs) is also influenced by the absence of IL-12/IL-23, bone marrow-derived DCs from IL-12/IL-23−/− and C57BL/6 mice were evaluated. At first we noticed that ≈ 50% of the C57BL/6 DCs were dead after LPS-induced maturation, whereas the mortality of IL-12/IL-23−/− DCs was < 10%, a protective effect that diminished when recombinant IL-12 (rIL-12) was added during maturation. Similarly to macrophages, mature IL-12/IL-23−/− DCs (mDCs) produced higher levels of TGF-β1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN-γ-dependent, as evidenced by the poor response of IFN-γ−/− and IL-12/IL-23−/−IFN-γ−/− mDCs. Nevertheless, IFN-γ deficiency was not the sole reason for the weak NO response observed in the absence of IL-12/IL-23. The high level of TGF-β1 secretion by IL-12/IL-23−/− mDCs could explain why exogenous IFN-γ partially restored the NO production of IFN-γ−/− mDCs, while IL-12/IL-23−/− IFN-γ−/− mDCs remained unresponsive. We also showed that CD4+ T-cell proliferation was inhibited by C57BL/6 mDCs, but not by IL-12/IL-23−/− mDCs. IFN-γ and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN-γ−/− or IL-12/IL-23−/− IFN-γ−/− mice and it was attenuated by aminoguanidine. We conclude that the presence of IL-12/IL-23 during LPS-induced maturation influences the activation profile of DCs by a mechanism that is, only in part, IFN-γ dependent. PMID:15804287

The Role of Telehealth to Assist In-Home tDCS: Opportunities, Promising Results and Acceptability

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Brenton Hordacre

2018-06-01

Full Text Available Transcranial direct current stimulation (tDCS has shown great promise as a neuromodulatory intervention capable of improving behavioral outcomes in a range of neurological and psychiatric populations. Evidence indicates that the neuromodulatory effect of stimulation may be cumulative, with greater improvements in behavior observed following multiple treatment sessions. However, the requirement to attend clinical or research departments for multiple treatment sessions may present a barrier for many people, particularly those with greater disability or living remotely. The portability of tDCS suggests that in-home stimulation may become an avenue for further investigation. However, safe and effective use of tDCS by a participant within their home requires a form of monitoring. This review discusses how telehealth may provide real-time visual monitoring to ensure correct tDCS set-up and adherence to stimulation protocols, manage technical issues and monitor adverse events. The combination of telehealth to supplement in-home tDCS use has potential to transform the way tDCS is delivered.

JACoW ADAPOS: An architecture for publishing ALICE DCS conditions data

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Lång, John; Bond, Peter; Chochula, Peter; Kurepin, Alexander; Lechman, Mateusz; Pinazza, Ombretta

2018-01-01

ALICE Data Point Service (ADAPOS) is a software architecture being developed for the RUN3 period of LHC, as a part of the effort to transmit conditions data from ALICE Detector Control System (DCS) to Event Processing Network (EPN), for distributed processing. The key processes of ADAPOS, Engine and Terminal, run on separate machines, facing different networks. Devices connected to DCS publish their state as DIM services. Engine gets updates to the services, and converts them into a binary stream. Terminal receives it over 0MQ, and maintains an image of the DCS state. It sends copies of the image, at regular intervals, over another 0MQ connection, to a readout process of ALICE Data Acquisition.

The Immunomodulatory Potential of tolDCs Loaded with Heat Shock Proteins

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Willem van Eden

2017-11-01

Full Text Available Disease suppressive T cell regulation may depend on cognate interactions of regulatory T cells with self-antigens that are abundantly expressed in the inflamed tissues. Heat shock proteins (HSPs are by their nature upregulated in stressed cells and therefore abundantly present as potential targets for such regulation. HSP immunizations have led to inhibition of experimentally induced inflammatory conditions in various models. However, re-establishment of tolerance in the presence of an ongoing inflammatory process has remained challenging. Since tolerogenic DCs (tolDCs have the combined capacity of mitigating antigen-specific inflammatory responses and of endowing T cells with regulatory potential, it seems attractive to combine the anti-inflammatory qualities of tolDCs with those of HSPs.

Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis

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Bahr, Matthias J.; Boeker, Klaus H. W.; Manns, Michael P.; Tietge, Uwe J. F.

Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis.

The effects of tDCS upon sustained visual attention are dependent on cognitive load.

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Roe, James M; Nesheim, Mathias; Mathiesen, Nina C; Moberget, Torgeir; Alnæs, Dag; Sneve, Markus H

2016-01-08

Transcranial Direct Current Stimulation (tDCS) modulates the excitability of neuronal responses and consequently can affect performance on a variety of cognitive tasks. However, the interaction between cognitive load and the effects of tDCS is currently not well-understood. We recorded the performance accuracy of participants on a bilateral multiple object tracking task while undergoing bilateral stimulation assumed to enhance (anodal) and decrease (cathodal) neuronal excitability. Stimulation was applied to the posterior parietal cortex (PPC), a region inferred to be at the centre of an attentional tracking network that shows load-dependent activation. 34 participants underwent three separate stimulation conditions across three days. Each subject received (1) left cathodal / right anodal PPC tDCS, (2) left anodal / right cathodal PPC tDCS, and (3) sham tDCS. The number of targets-to-be-tracked was also manipulated, giving a low (one target per visual field), medium (two targets per visual field) or high (three targets per visual field) tracking load condition. It was found that tracking performance at high attentional loads was significantly reduced in both stimulation conditions relative to sham, and this was apparent in both visual fields, regardless of the direction of polarity upon the brain's hemispheres. We interpret this as an interaction between cognitive load and tDCS, and suggest that tDCS may degrade attentional performance when cognitive networks become overtaxed and unable to compensate as a result. Systematically varying cognitive load may therefore be a fruitful direction to elucidate the effects of tDCS upon cognitive functions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

LILRB4 Decrease on uDCs Exacerbate Abnormal Pregnancy Outcomes Following Toxoplasma gondii Infection

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Shaowei Zhan

2018-03-01

Full Text Available Toxoplasma gondii (T. gondii infection in early pregnancy can result in miscarriage, dead fetus, and other abnormalities. The LILRB4 is a central inhibitory receptor in uterine dendritic cells (uDCs that plays essential immune-regulatory roles at the maternal–fetal interface. In this study, T. gondii-infected human primary uDCs and T. gondii-infected LILRB4-/- pregnant mice were utilized. The immune mechanisms underlying the role of LILRB4 on uDCs were explored in the development of abnormal pregnancy outcomes following T. gondii infection in vitro and in vivo. Our results showed that the expression levels of LILRB4 on uDCs from normal pregnant mice were obviously higher than non-pregnant mice, and peaked in mid-gestation. The LILRB4 expression on uDC subsets, especially tolerogenic subsets, from mid-gestation was obviously down-regulated after T. gondii infection and LILRB4 decrease could further regulate the expression of functional molecules (CD80, CD86, and HLA-DR or MHC II on uDCs, contributing to abnormal pregnancy outcomes. Our results will shed light on the molecular immune mechanisms of uDCs in abnormal pregnancy outcomes by T. gondii infection.

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS

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Natalie Dittert

2018-04-01

Full Text Available Although posttraumatic stress disorder (PTSD; DSM-V 309.82 and anxiety disorders (DSM-V 300.xx are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS and a 95-dB female scream as unconditioned stimulus (UCS. We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC, which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84. The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS– discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS– in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be

Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition

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Murphy, Jillian M.; Ridley, Nicole J.; Vercammen, Ans

2015-01-01

The orbitofrontal cortex (OFC) has been implicated in the capacity to accurately recognise facial expressions. The aim of the current study was to determine if anodal transcranial direct current stimulation (tDCS) targeting the right OFC in healthy adults would enhance facial expression recognition, compared with a sham condition. Across two counterbalanced sessions of tDCS (i.e. anodal and sham), 20 undergraduate participants (18 female) completed a facial expression labelling task comprising angry, disgusted, fearful, happy, sad and neutral expressions, and a control (social judgement) task comprising the same expressions. Responses on the labelling task were scored for accuracy, median reaction time and overall efficiency (i.e. combined accuracy and reaction time). Anodal tDCS targeting the right OFC enhanced facial expression recognition, reflected in greater efficiency and speed of recognition across emotions, relative to the sham condition. In contrast, there was no effect of tDCS to responses on the control task. This is the first study to demonstrate that anodal tDCS targeting the right OFC boosts facial expression recognition. This finding provides a solid foundation for future research to examine the efficacy of this technique as a means to treat facial expression recognition deficits, particularly in individuals with OFC damage or dysfunction. PMID:25971602

tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

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Vanderhasselt, Marie-Anne; De Raedt, Rudi; Brunoni, Andre R; Campanhã, Camila; Baeken, Chris; Remue, Jonathan; Boggio, Paulo S

2013-01-01

Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP) as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation), we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right) prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

No significant effect of prefrontal tDCS on working memory performance in older adults

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Jonna eNilsson

2015-12-01

Full Text Available Transcranial direct current stimulation (tDCS has been put forward as a non-pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dlPFC on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1mA and 2mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dlPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

Molecular and elemental effects underlying the biochemical action of transcranial direct current stimulation (tDCS) in appetite control

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Surowka, Artur D.; Ziomber, Agata; Czyzycki, Mateusz; Migliori, Alessandro; Kasper, Kaja; Szczerbowska-Boruchowska, Magdalena

2018-04-01

Recent studies highlight that obesity may alter the electric activity in brain areas triggering appetite and craving. Transcranial direct current brain stimulation (tDCS) has recently emerged as a safe alternative for treating food addiction via modulating cortical excitability without any high-risk surgical procedure to be utilized. As for anodal-type tDCS (atDCS), we observe increased excitability and spontaneous firing of the cortical neurons, whilst for the cathodal-type tDCS (ctDCS) a significant decrease is induced. Unfortunately, for the method to be fully used in a clinical setting, its biochemical action mechanism must be precisely defined, although it is proposed that molecular remodelling processes play in concert with brain activity changes involving the ions of: Na, Cl, K and Ca. Herein, we proposed for the first time Fourier transform infrared (FTIR) and synchrotron X-ray fluorescence (SRXRF) microprobes for a combined molecular and elemental analysis in the brain areas implicated appetite control, upon experimental treatment by either atDCS or ctDCS. The study, although preliminary, shows that by stimulating the prefrontal cortex in the rats fed high-caloric nutrients, the feeding behavior can be significantly changed, resulting in significantly inhibited appetite. Both, atDCS and ctDCS produced significant molecular changes involving qualitative and structural properties of lipids, whereas atDCS was found with a somewhat more significant effect on protein secondary structure in all the brain areas investigated. Also, tDCS was reported to reduce surface masses of Na, Cl, K, and Ca in almost all brain areas investigated, although the atDCS deemed to have a stronger neuro-modulating effect. Taken together, one can report that tDCS is an effective treatment technique, and its action mechanism in the appetite control seems to involve a variety of lipid-, protein- and metal/non-metal-ion-driven biochemical changes, regardless the current polarization.

Remotely-Supervised Transcranial Direct Current Stimulation (tDCS for Clinical Trials: Guidelines for Technology and Protocols

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Leigh E Charvet

2015-03-01

Full Text Available The effect of transcranial direct current stimulation (tDCS is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: 1 training of staff in tDCS treatment and supervision, 2 assessment of the user’s capability to participate in tDCS remotely, 3 ongoing training procedures and materials including assessments of the user and/or caregiver, 4 simple and fail-safe electrode preparation techniques and tDCS headgear, 5 strict dose control for each session, 6 ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol, with corresponding corrective steps as required, 7 monitoring for treatment-emergent adverse effects, 8 guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population’s level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Dual-tDCS Enhances Online Motor Skill Learning and Long-Term Retention in Chronic Stroke Patients

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Lefebvre, S.; Laloux, P.; Peeters, A.; Desfontaines, P.; Jamart, J.; Vandermeeren, Y.

2013-01-01

Background: Since motor learning is a key component for stroke recovery, enhancing motor skill learning is a crucial challenge for neurorehabilitation. Transcranial direct current stimulation (tDCS) is a promising approach for improving motor learning. The aim of this trial was to test the hypothesis that dual-tDCS applied bilaterally over the primary motor cortices (M1) improves online motor skill learning with the paretic hand and its long-term retention. Methods: Eighteen chronic stroke patients participated in a randomized, cross-over, placebo-controlled, double bind trial. During separate sessions, dual-tDCS or sham dual-tDCS was applied over 30 min while stroke patients learned a complex visuomotor skill with the paretic hand: using a computer mouse to move a pointer along a complex circuit as quickly and accurately as possible. A learning index involving the evolution of the speed/accuracy trade-off was calculated. Performance of the motor skill was measured at baseline, after intervention and 1 week later. Results: After sham dual-tDCS, eight patients showed performance worsening. In contrast, dual-tDCS enhanced the amount and speed of online motor skill learning compared to sham (p dual-tDCS (n = 10) than after sham (n = 3). More importantly, 1 week later, online enhancement under dual-tDCS had translated into superior long-term retention (+44%) compared to sham (+4%). The improvement generalized to a new untrained circuit and to digital dexterity. Conclusion: A single-session of dual-tDCS, applied while stroke patients trained with the paretic hand significantly enhanced online motor skill learning both quantitatively and qualitatively, leading to successful long-term retention and generalization. The combination of motor skill learning and dual-tDCS is promising for improving post-stroke neurorehabilitation. PMID:23316151

Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test.

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Sellers, Kristin K; Mellin, Juliann M; Lustenberger, Caroline M; Boyle, Michael R; Lee, Won Hee; Peterchev, Angel V; Fröhlich, Flavio

2015-09-01

Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants were included in the final analysis. These participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2 mA at each anode for 20 min) or active sham tDCS (2 mA for 40 s), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2 mA for 20 min). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. Copyright © 2015 Elsevier B.V. All rights reserved.

tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

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Marie-Anne Vanderhasselt

Full Text Available Transcranial Direct Current Stimulation (tDCS is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation, we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

tDCS stimulation segregates words in the brain: evidence from aphasia

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Valentina eFiori

2013-06-01

Full Text Available A number of studies have already shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS improves noun or verb naming in aphasic patients. However, it is not yet clear whether these effects are equally obtained through stimulation over the frontal or the temporal regions. In the present study, the same group of aphasic subjects participated in two randomized double-blind experiments involving two intensive language treatments for their noun and verb retrieval difficulties. During each training, each subject was treated with tDCS (20 min., 1mA over the left hemisphere in three different conditions: anodic tDCS over the temporal areas, anodic tDCS over the frontal areas and sham stimulation, while they performed a noun and an action naming tasks. Each experimental condition was run in five consecutive daily sessions over three weeks with 6 days of intersession interval. The order of administration of the two language trainings was randomly assigned to all patients. Overall, with respect to the other two conditions, results showed a significant greater improvement in noun naming after stimulation over the temporal region, while verb naming recovered significantly better after stimulation of the frontal region. These improvements persisted at one month after the end of each treatment suggesting a long-term effect on recovery of the patients’ noun and verb difficulties. These data clearly suggest that the mechanisms of recovery for naming can be segregated coupling tDCS with an intensive language training.

Cerebellar tDCS does not affect performance in the N-back task.

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van Wessel, Brenda W V; Claire Verhage, M; Holland, Peter; Frens, Maarten A; van der Geest, Jos N

2016-01-01

The N-back task is widely used in cognitive research. Furthermore, the cerebellum's role in cognitive processes is becoming more widely recognized. Studies using transcranial direct current stimulation (tDCS) have demonstrated effects of cerebellar stimulation on several cognitive tasks. Therefore, the aim of this study was to investigate the effects of cerebellar tDCS on cognitive performance by using the N-back task. The cerebellum of 12 participants was stimulated during the task. Moreover, the cognitive load was manipulated in N = 2, N = 3, and N = 4. Every participant received three tDCS conditions (anodal, cathodal, and sham) divided over three separated days. It was expected that anodal stimulation would improve performance on the task. Each participant performed 6 repetitions of every load in which correct responses, false alarms, and reaction times were recorded. We found significant differences between the three levels of load in the rate of correct responses and false alarms, indicating that subjects followed the expected pattern of performance for the N-back task. However, no significant differences between the three tDCS conditions were found. Therefore, it was concluded that in this study cognitive performance on the N-back task was not readily influenced by cerebellar tDCS, and any true effects are likely to be small. We discuss several limitations in task design and suggest future experiments to address such issues.

Cerebellar tDCS does not enhance performance in an implicit categorization learning task

NARCIS (Netherlands)

M.C. Verhage (Claire); E. Avila (Eric); M.A. Frens (Maarten); O. Donchin (Opher); J.N. van der Geest (Jos)

2017-01-01

textabstractBackground: Transcranial Direct Current Stimulation (tDCS) is a form of non-invasive electrical stimulation that changes neuronal excitability in a polarity and site-specific manner. In cognitive tasks related to prefrontal and cerebellar learning, cortical tDCS arguably facilitates

Transcranial direct current stimulation (tDCS) to the supplementary motor area (SMA) influences performance on motor tasks.

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Hupfeld, K E; Ketcham, C J; Schneider, H D

2017-03-01

The supplementary motor area (SMA) is believed to be highly involved in the planning and execution of both simple and complex motor tasks. This study aimed to examine the role of the SMA in planning the movements required to complete reaction time, balance, and pegboard tasks using anodal transcranial direct current stimulation (tDCS), which passes a weak electrical current between two electrodes, in order to modulate neuronal activity. Twenty healthy adults were counterbalanced to receive either tDCS (experimental condition) or no tDCS (control condition) for 3 days. During administration of tDCS, participants performed a balance task significantly faster than controls. After tDCS, subjects significantly improved their simple and choice reaction time. These results demonstrate that the SMA is highly involved in planning and executing fine and gross motor skill tasks and that tDCS is an effective modality for increasing SMA-related performance on these tasks. The findings may be generalizable and therefore indicate implications for future interventions using tDCS as a therapeutic tool.

Neonatal plasmacytoid dendritic cells (pDCs display subset variation but can elicit potent anti-viral innate responses.

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Xiaoming Zhang

Full Text Available Neonates are highly susceptible to infectious diseases and defective antiviral pDC immune responses have been proposed to contribute to this phenomenon. Isolated cord blood pDCs innately responded to a variety of TLR7 and TLR9 dependent viruses, including influenza A virus (IAV, human immunodeficiency virus (HIV or herpes-simplex virus (HSV by efficiently producing IFN-α, TNF-α as well as chemokines. Interestingly, following activation by CpGA, but not viruses, cord pDCs tend to survive less efficiently. We found that a hallmark of pDCs in neonates is an extended CD2+pDCs compartment compared to adult pDCs without affecting the antiviral IFN-α response. Within CD2+pDCs, we identified a subpopulation expressing CD5 and responsible for IL-12p40 production, however this population is significantly decreased in cord blood compared to adult blood. Therefore, neonatal pDCs clearly display variation in phenotype and subset composition, but without major consequences for their antiviral responses.

Applying anodal tDCS during tango dancing in a patient with Parkinson's disease.

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Kaski, D; Allum, J H; Bronstein, A M; Dominguez, R O

2014-05-07

Gait disturbance in patients with Parkinson's disease remains a therapeutic challenge, given its poor response to levodopa. Dance therapy is of recognised benefit in these patients, particularly partnered dance forms such as the tango. In parallel, non-invasive brain stimulation has begun to show promise for the rehabilitation of patients with Parkinson's disease, although effects on gait, compared to upper limbs, have been less well defined. We applied transcranial direct current stimulation (tDCS) in a 79 year old male patient with moderate Parkinson's disease during tango dancing to assess its effect on trunk motion and balance. The patient performed a total of four dances over two days, two 'tango+tDCS' and two 'tango+sham' in a randomised double-blind fashion. In a separate experimental session we also assessed the isolated effect of tDCS (and sham) on gait without tango dancing. For the dance session, trunk peak velocity during tango was significantly greater during tDCS compared to sham stimulation. In the gait experiments we observed a modest but significant reduction in the time taken to complete the 3m 'timed up and go' and 6m walk, and an increase in overall gait velocity and peak pitch trunk velocity with tDCS compared to sham. Our findings suggest that tDCS may be a useful adjunct to gait rehabilitation for patients with PD, although studies in a larger group of patients are needed to evaluate the therapeutic use of non-invasive brain stimulation during dance therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

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Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2016-01-30

Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comprehensive evaluation method in application of nuclear DCS product design

International Nuclear Information System (INIS)

Wang Weixin; Zhao Zhemin; Shi Yingbin

2014-01-01

In order to select the best design proposal in short time, the TOPSIS comprehensive evaluation method in the nuclear power plant DCS product design was introduced. It can intuitively show the different design proposals good or not good by data and shorten the time of the design proposal optimization. The design proposal selected by this method will be more reasonable and has good comprehensive performance indexes. The TOPSIS comprehensive evaluation method achieves good result in one of the nuclear power plant DCS cabinet design proposal optimization. (authors)

Transcranial Direct Current Stimulation and Power Spectral Parameters: a tDCS/EEG co-registration study

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Anna Lisa Mangia

2014-08-01

Full Text Available Transcranial direct current stimulation (tDCS delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta and gamma power bands were investigated. Three main findings emerged: 1 an increase in theta band activity during the first minutes of stimulation; 2 an increase in alpha and beta power during and after stimulation; 3 a widespread activation in several brain regions.

Increased contextual cue utilization with tDCS over the prefrontal cortex during a recognition task

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Pergolizzi, Denise; Chua, Elizabeth F.

2016-01-01

The precise role of the prefrontal and posterior parietal cortices in recognition performance remains controversial, with questions about whether these regions contribute to recognition via the availability of mnemonic evidence or via decision biases and retrieval orientation. Here we used an explicit memory cueing paradigm, whereby external cues probabilistically predict upcoming memoranda as old or new, in our case with 75% validity, and these cues affect recognition decision biases in the direction of the cue. The present study applied bilateral transcranial direct current stimulation (tDCS) over prefrontal or posterior parietal cortex, or sham tDCS, to test the causal role of these regions in recognition accuracy or decision biasing. Participants who received tDCS over prefrontal cortex showed increased cue utilization compared to tDCS over posterior parietal cortex and sham tDCS, suggesting that the prefrontal cortex is involved in processes that contribute to decision biases in memory. PMID:27845032

Motor/Prefrontal Transcranial Direct Current Stimulation (tDCS) Following Lumbar Surgery Reduces Postoperative Analgesia Use.

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Glaser, John; Reeves, Scott T; Stoll, William David; Epperson, Thomas I; Hilbert, Megan; Madan, Alok; George, Mark S; Borckardt, Jeffrey J

2016-05-01

Randomized, controlled pilot trial. The present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tDCS) for pain and patient-controlled analgesia (PCA) opioid usage among patients receiving spine surgery. Lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including tDCS are beginning to demonstrate promise as treatments for a variety of pain conditions. Twenty-seven patients undergoing lumbar spine procedures at Medical University of South Carolina were randomly assigned to receive four 20-minute sessions of real or sham tDCS during their postsurgical hospital stay. Patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. The effect of tDCS on the slope of the cumulative PCA curve was significant (P tDCS was associated with a 23% reduction in PCA usage. In the real tDCS group a 31% reduction was observed in pain-at-its-least ratings from admission to discharge (P = 0.027), but no other changes in numeric rating scale pain ratings were significant in either group. The present pilot trial is the first study to demonstrate an opioid sparing effect of tDCS after spine surgical procedures. Although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tDCS, suggesting that future work in this area is warranted. 2.

Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects?

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Wörsching, Jana; Padberg, Frank; Ertl-Wagner, Birgit; Kumpf, Ulrike; Kirsch, Beatrice; Keeser, Daniel

2016-10-01

Transcranial current stimulation approaches include neurophysiologically distinct non-invasive brain stimulation techniques widely applied in basic, translational and clinical research: transcranial direct current stimulation (tDCS), oscillating transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). Prefrontal tDCS seems to be an especially promising tool for clinical practice. In order to effectively modulate relevant neural circuits, systematic research on prefrontal tDCS is needed that uses neuroimaging and neurophysiology measures to specifically target and adjust this method to physiological requirements. This review therefore analyses the various neuroimaging methods used in combination with prefrontal tDCS in healthy and psychiatric populations. First, we provide a systematic overview on applications, computational models and studies combining neuroimaging or neurophysiological measures with tDCS. Second, we categorise these studies in terms of their experimental designs and show that many studies do not vary the experimental conditions to the extent required to demonstrate specific relations between tDCS and its behavioural or neurophysiological effects. Finally, to support best-practice tDCS research we provide a methodological framework for orientation among experimental designs. Copyright © 2016 Elsevier Ltd. All rights reserved.

DCS-Neural-Network Program for Aircraft Control and Testing

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Jorgensen, Charles C.

2006-01-01

A computer program implements a dynamic-cell-structure (DCS) artificial neural network that can perform such tasks as learning selected aerodynamic characteristics of an airplane from wind-tunnel test data and computing real-time stability and control derivatives of the airplane for use in feedback linearized control. A DCS neural network is one of several types of neural networks that can incorporate additional nodes in order to rapidly learn increasingly complex relationships between inputs and outputs. In the DCS neural network implemented by the present program, the insertion of nodes is based on accumulated error. A competitive Hebbian learning rule (a supervised-learning rule in which connection weights are adjusted to minimize differences between actual and desired outputs for training examples) is used. A Kohonen-style learning rule (derived from a relatively simple training algorithm, implements a Delaunay triangulation layout of neurons) is used to adjust node positions during training. Neighborhood topology determines which nodes are used to estimate new values. The network learns, starting with two nodes, and adds new nodes sequentially in locations chosen to maximize reductions in global error. At any given time during learning, the error becomes homogeneously distributed over all nodes.

Transcranial Direct Current Stimulation (tDCS: A Beginner's Guide for Design and Implementation

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Hayley Thair

2017-11-01

Full Text Available Transcranial direct current stimulation (tDCS is a popular brain stimulation method that is used to modulate cortical excitability, producing facilitatory or inhibitory effects upon a variety of behaviors. There is, however, a current lack of consensus between studies, with many results suggesting that polarity-specific effects are difficult to obtain. This article explores some of these differences and highlights the experimental parameters that may underlie their occurrence. We provide a general, practical snapshot of tDCS methodology, including what it is used for, how to use it, and considerations for designing an effective and safe experiment. Our aim is to equip researchers who are new to tDCS with the essential knowledge so that they can make informed and well-rounded decisions when designing and running successful experiments. By summarizing the varied approaches, stimulation parameters, and outcomes, this article should help inform future tDCS research in a variety of fields.

Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and Implementation

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Thair, Hayley; Holloway, Amy L.; Newport, Roger; Smith, Alastair D.

2017-01-01

Transcranial direct current stimulation (tDCS) is a popular brain stimulation method that is used to modulate cortical excitability, producing facilitatory or inhibitory effects upon a variety of behaviors. There is, however, a current lack of consensus between studies, with many results suggesting that polarity-specific effects are difficult to obtain. This article explores some of these differences and highlights the experimental parameters that may underlie their occurrence. We provide a general, practical snapshot of tDCS methodology, including what it is used for, how to use it, and considerations for designing an effective and safe experiment. Our aim is to equip researchers who are new to tDCS with the essential knowledge so that they can make informed and well-rounded decisions when designing and running successful experiments. By summarizing the varied approaches, stimulation parameters, and outcomes, this article should help inform future tDCS research in a variety of fields. PMID:29213226

Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS): Clinical Applications and Safety Concerns

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Zhao, Haichao; Qiao, Lei; Fan, Dongqiong; Zhang, Shuyue; Turel, Ofir; Li, Yonghui; Li, Jun; Xue, Gui; Chen, Antao; He, Qinghua

2017-01-01

Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation. PMID:28539894

New Concept For Alarm Structure And Management In Dcs Systems

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Mohammed Hegazy

2015-08-01

Full Text Available The objective of this paper is to set new standard for good design and best practice to applied when any DCS ManufacturesSuppliers configure process alarm system in any oil refining oil and gas production gas-handling facilities gasification plant or any chemical processing plant and thereby to optimizeminimize unnecessary alarms from reporting to operator workstations CAD Control Alarm Display. These views based on the experience acquired and implemented during involvement with the commissioning and startup of two DCS projects in Mina Al-Ahmadi Refinery Kuwait.

A reliability evaluation method for NPP safety DCS application software

International Nuclear Information System (INIS)

Li Yunjian; Zhang Lei; Liu Yuan

2014-01-01

In the field of nuclear power plant (NPP) digital i and c application, reliability evaluation for safety DCS application software is a key obstacle to be removed. In order to quantitatively evaluate reliability of NPP safety DCS application software, this paper propose a reliability evaluating method based on software development life cycle every stage's v and v defects density characteristics, by which the operating reliability level of the software can be predicted before its delivery, and helps to improve the reliability of NPP safety important software. (authors)

Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis.

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Imburgio, Michael J; Orr, Joseph M

2018-05-01

A meta-analysis of studies using single-session transcranial direct current stimulation (tDCS) to target the dorsolateral prefrontal cortex (DLPFC) was undertaken to examine the effect of stimulation on executive function (EF) in healthy samples. 27 studies were included in analyses, yielding 71 effect sizes. The most relevant measure for each task was determined a priori and used to calculate Hedge's g. Methodological characteristics of each study were examined individually as potential moderators of effect size. Stimulation effects on three domains of EF (inhibition of prepotent responses, mental set shifting, and information updating and monitoring) were analyzed separately. In line with previous work, the current study found no significant effect of anodal unilateral tDCS, cathodal unilateral tDCS, or bilateral tDCS on EF. Further moderator and subgroup analyses were only carried out for anodal unilateral montages due to the small number of studies using other montages. Subgroup analyses revealed a significant effect of anodal unilateral tDCS on updating tasks, but not on inhibition or set-shifting tasks. Cathode location significantly moderated the effect of anodal unilateral tDCS. Extracranial cathodes yielded a significant effect on EF while cranial cathodes yielded no effect. Anode size also significantly moderated effect of anodal unilateral tDCS, with smaller anodes being more effective than larger anodes. In summary, anodal DLPFC stimulation is more effective at improving updating ability than inhibition and set-shifting ability, but anodal stimulation can significantly improve general executive function when extracranial cathodes or small anodes are used. Future meta-analyses may examine how stimulation's effects on specific behavioral tasks, rather than broader domains, might be affected by methodological moderators. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of effect of safety classification on DCS design in nuclear power plants

International Nuclear Information System (INIS)

Gou Guokai; Li Guomin; Wang Qunfeng

2011-01-01

By analyzing the safety classification for the systems and functions of nuclear power plants based on the general design requirements for nuclear power plants, especially the requirement of availability and reliability of I and C systems, the characteristics of modem DCS technology and I and C products currently applied in nuclear power field are interpreted. According to the requirements on the safety operation of nuclear power plants and the regulations for safety audit, the effect of different safety classifications on DCS design in nuclear power plants is analyzed, by considering the actual design process of different DCS solutions in the nuclear power plants under construction. (authors)

Building up analgesia in humans via the endogenous μ-opioid system by combining placebo and active tDCS: a preliminary report.

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Marcos F DosSantos

Full Text Available Transcranial Direct Current Stimulation (tDCS is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience. Nine healthy volunteers went through positron emission tomography (PET scans with [11C]carfentanil, a selective μ-opioid receptor (MOR radiotracer, to measure the central MOR activity during tDCS in vivo (non-displaceable binding potential, BPND--one of the main analgesic mechanisms in the brain. Placebo and real anodal primary motor cortex (M1/2mA tDCS were delivered sequentially for 20 minutes each during the PET scan. The initial placebo tDCS phase induced a decrease in MOR BPND in the periaqueductal gray matter (PAG, precuneus, and thalamus, indicating activation of endogenous μ-opioid neurotransmission, even before the active tDCS. The subsequent real tDCS also induced MOR activation in the PAG and precuneus, which were positively correlated to the changes observed with placebo tDCS. Nonetheless, real tDCS had an additional MOR activation in the left prefrontal cortex. Although significant changes in the MOR BPND occurred with both placebo and real tDCS, significant analgesic effects, measured by improvements in the heat and cold pain thresholds, were only observed after real tDCS, not the placebo tDCS. This study gives preliminary evidence that the analgesic effects reported with M1-tDCS, can be in part related to the recruitment of the same endogenous MOR mechanisms induced by placebo, and that such effects can be purposely optimized by real tDCS.

Multi-session transcranial direct current stimulation (tDCS elicits inflammatory and regenerative processes in the rat brain.

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Maria Adele Rueger

Full Text Available Transcranial direct current stimulation (tDCS is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16 were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min. Bromodeoxyuridine (BrdU was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC. Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

Antigen Loading (e.g., Glutamic Acid Decarboxylase 65 of Tolerogenic DCs (tolDCs 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

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David P. Funda

2018-02-01

Full Text Available Tolerogenic DCs (tolDCs are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D. T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65, that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD-severe combined immunodeficiency (NOD-SCID recipients. While i.p. application of tolDCs prepared from bone marrow of prediabetic NOD mice by vitamin D2 and dexamethasone significantly reduced diabetes transfer into the NOD-SCID females, this effect was completely abolished when tolDCs were loaded with the mouse recombinant GAD65, but also with a control protein—ovalbumin (OVA. The effect was not dependent on the presence of serum in the tolDC culture. Similar results were observed in NOD mice. Removal of possible bystander antigen-presenting cells within the diabetogenic splenocytes by negative magnetic sorting of T cells did not alter this surprising effect. Tolerogenic DCs loaded with an immunodominant mouse GAD65 peptide also displayed diminished diabetes-preventive effect. Tolerogenic DCs were characterized by surface maturation markers (CD40, CD80, CD86, MHC II and the lipopolysaccharide stability test. Data from alloreactive T cell proliferation and cytokine induction assays (IFN-γ did not reveal the differences observed in the diabetes incidence. Migration of tolDCs, tolDCs-GAD65 and tolDCs-OVA to spleen, mesenteric- and pancreatic lymph nodes displayed similar, mucosal pattern with highest accumulation in pancreatic lymph nodes present up to 9 days after the i.p. application. These data document that mechanisms by which tolDCs

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified aromatic-turmerone (AR).

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Yonggang, Tan; Yiming, Meng; Heying, Zhang; Cheng, Sun; Qiushi, Wang; Xianghong, Yang; Wei, Zheng; Huawei, Zhou; Shan, Fengping

2012-10-01

The aim of this work is to evaluate the effects of purified aromatic-turmerone (ar-turmerione, AR) on murine dendritic cells (DCs). These impacts of AR on DCs from bone marrow derived DCs(BMDCs) were assessed with use of conventional scanning electron microscopy (SEM), fluorescence activated cell sorting (FACS), transmission electron microscopy (TEM), cytochemistry assay, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA). We found that AR induced phenotypic maturation as evidenced by increased expression of CD86, CD40, CD83, CD80 and major histocompatibility complex II (MHC II). The functional tests showed the activity of acidic phosphatase (ACP) inside the DCs were downregulated after treatment with AR (which occurs when phagocytosis of DCs were decreased). Finally, we proved that AR increased the production of IL-12 and tumor necrosis factor α (TNF-α). These data suggested that AR could promote phenotypic and functional maturation of DCs and this adjuvant-like activity may have potential therapeutic value. It is therefore concluded that AR could exert positive modulation on murine DCs.

Impact of DCS-facilitated cue exposure therapy on brain activation to cocaine cues in cocaine dependence.

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Prisciandaro, James J; Myrick, Hugh; Henderson, Scott; McRae-Clark, Aimee L; Santa Ana, Elizabeth J; Saladin, Michael E; Brady, Kathleen T

2013-09-01

The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence. Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training. Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not. Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anodal-tDCS over the human right occipital cortex enhances the perception and memory of both faces and objects.

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Barbieri, Marica; Negrini, Marcello; Nitsche, Michael A; Rivolta, Davide

2016-01-29

Accurate face processing skills are pivotal for typical social cognition, and impairments in this ability characterise various clinical conditions (e.g., prosopagnosia). No study to date has investigated whether transcranial direct current stimulation (tDCS) can causally enhance face processing. In addition, the category- and the process-specificity of tDCS effects, as well as the role of the timing of neuromodulation with respect to the execution of cognitive tasks are still unknown. In this single-blind, sham-controlled study, we examined whether the administration of anodal-tDCS (a-tDCS) over the right occipital cortex of healthy volunteers (N=64) enhances performance on perceptual and memory tasks involving both face and object stimuli. Neuromodulation was delivered in two conditions: online (a-tDCS during task execution) and offline (a-tDCS before task execution). The results demonstrate that offline a-tDCS enhances the perception and memory performance of both faces and objects. There was no effect of online a-tDCS on behaviour. Furthermore, the offline effect was site-specific since a-tDCS over the sensory-motor cortex did not lead to behavioural changes. Our results add relevant information about the breadth of cognitive processes and visual stimuli that can be modulated by tDCS, and about the design of effective neuromodulation protocols, which have implications for advancing theories in cognitive neuroscience and clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age

DEFF Research Database (Denmark)

Fisker, Ane B; Lisse, Ida M; Aaby, Peter

2007-01-01

concentrations indicated vitamin A deficiency in 32% of the children at age 6 wk and in 16% at age 4 mo. VAS was not associated with higher RBP concentrations overall or in either sex. However, the effect of VAS varied with maternal education (P for interaction = 0.004): At age 6 wk, VAS was associated...... with higher (9%; 95% CI: 2, 17%) RBP concentrations in children of noneducated mothers but not in children of educated mothers. Overall, RBP concentrations increased between 6 wk and 4 mo of age. The increase correlated inversely with the number of diphtheria-tetanus-pertussis (DTP) vaccines received...... placebo-controlled trial of VAS, we obtained blood from 614 children at 6 wk of age and from 369 mother-infant pairs at 4 mo of age. We assessed vitamin A status on the basis of serum retinol-binding protein (RBP) and measured serum C-reactive protein to monitor for concurrent infections. RESULTS: RBP...

[Transcranial direct current stimulation (tDCS) for depression: Results of nearly a decade of clinical research].

Science.gov (United States)

Palm, U; Ayache, S S; Padberg, F; Lefaucheur, J-P

2016-02-01

Since 2006 transcranial direct current stimulation (tDCS) has been investigated in the treatment of depression. In this review, we discuss the implications and clinical perspectives that tDCS may have as a therapeutic tool in depression from the results reported in this domain. A comprehensive literature review has found nearly thirty articles - all in English - on this topic, corresponding to clinical studies, placebo-controlled or not, case reports and reviews. Several meta-analyses showed that the antidepressant effects of active tDCS are significant against placebo, but variable, mainly due to the heterogeneity of the patients included in the studies, for example regarding the resistance to antidepressant treatment. Specific recommendations for the use of tDCS in treating depression may not yet be available, but some elements of good practice can be highlighted. Of particular note is that anodal tDCS of the left prefrontal cortex at 2mA for 20 minutes per day has a potential therapeutic value without risk of significant side effects: tDCS offers safe conditions for clinical use in the treatment of depression. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Low Intensity Focused tDCS Over the Motor Cortex Shows Inefficacy to Improve Motor Imagery Performance

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Irma N. Angulo-Sherman

2017-07-01

Full Text Available Transcranial direct current stimulation (tDCS is a brain stimulation technique that can enhance motor activity by stimulating the motor path. Thus, tDCS has the potential of improving the performance of brain-computer interfaces during motor neurorehabilitation. tDCS effects depend on several aspects, including the current density, which usually varies between 0.02 and 0.08 mA/cm2, and the location of the stimulation electrodes. Hence, testing tDCS montages at several current levels would allow the selection of current parameters for improving stimulation outcomes and the comparison of montages. In a previous study, we found that cortico-cerebellar tDCS shows potential of enhancing right-hand motor imagery. In this paper, we aim to evaluate the effects of the focal stimulation of the motor cortex over motor imagery. In particular, the effect of supplying tDCS with a 4 × 1 ring montage, which consists in placing an anode on the motor cortex and four cathodes around it, over motor imagery was assessed with different current densities. Electroencephalographic (EEG classification into rest or right-hand/feet motor imagery was evaluated on five healthy subjects for two stimulation schemes: applying tDCS for 10 min on the (1 right-hand or (2 feet motor cortex before EEG recording. Accuracy differences related to the tDCS intensity, as well as μ and β band power changes, were tested for each subject and tDCS modality. In addition, a simulation of the electric field induced by the montage was used to describe its effect on the brain. Results show no improvement trends on classification for the evaluated currents, which is in accordance with the observation of variable EEG band power results despite the focused stimulation. The lack of effects is probably related to the underestimation of the current intensity required to apply a particular current density for small electrodes and the relatively short inter-electrode distance. Hence, higher current

The impact of cerebellar transcranial direct current stimulation (tDCS) on learning fine-motor sequences.

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Shimizu, Renee E; Wu, Allan D; Samra, Jasmine K; Knowlton, Barbara J

2017-01-05

The cerebellum has been shown to be important for skill learning, including the learning of motor sequences. We investigated whether cerebellar transcranial direct current stimulation (tDCS) would enhance learning of fine motor sequences. Because the ability to generalize or transfer to novel task variations or circumstances is a crucial goal of real world training, we also examined the effect of tDCS on performance of novel sequences after training. In Study 1, participants received either anodal, cathodal or sham stimulation while simultaneously practising three eight-element key press sequences in a non-repeating, interleaved order. Immediately after sequence practice with concurrent tDCS, a transfer session was given in which participants practised three interleaved novel sequences. No stimulation was given during transfer. An inhibitory effect of cathodal tDCS was found during practice, such that the rate of learning was slowed in comparison to the anodal and sham groups. In Study 2, participants received anodal or sham stimulation and a 24 h delay was added between the practice and transfer sessions to reduce mental fatigue. Although this consolidation period benefitted subsequent transfer for both tDCS groups, anodal tDCS enhanced transfer performance. Together, these studies demonstrate polarity-specific effects on fine motor sequence learning and generalization.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

Transcranial direct current stimulation (tDCS) for idiopathic Parkinson's disease.

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Elsner, Bernhard; Kugler, Joachim; Pohl, Marcus; Mehrholz, Jan

2016-07-18

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder, with the severity of the disability usually increasing with disease duration. IPD affects patients' health-related quality of life, disability, and impairment. Current rehabilitation approaches have limited effectiveness in improving outcomes in patients with IPD, but a possible adjunct to rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in IPD. To assess the effectiveness of tDCS in improving motor and non-motor symptoms in people with IPD. We searched the following databases (until February 2016): the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library ; 2016 , Issue 2), MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index, the Physiotherapy Evidence Database (PEDro), Rehabdata, and Inspec. In an effort to identify further published, unpublished, and ongoing trials, we searched trial registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials that compared tDCS versus control in patients with IPD for improving health-related quality of life , disability, and impairment. Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. We included six trials with a total of 137 participants. We found two studies with 45 participants examining the effects of tDCS compared to control (sham tDCS) on our primary outcome measure, impairment, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). There was very low quality evidence for no effect of tDCS on change in global UPDRS score ( mean

Evolution and variability of Solanum RanGAP2, a cofactor in the incompatible interaction between the resistance protein GPA2 and the Globodera pallida effector Gp-RBP-1.

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Carpentier, Jean; Grenier, Eric; Esquibet, Magalie; Hamel, Louis-Philippe; Moffett, Peter; Manzanares-Dauleux, Maria J; Kerlan, Marie-Claire

2013-04-19

The Ran GTPase Activating Protein 2 (RanGAP2) was first described as a regulator of mitosis and nucleocytoplasmic trafficking. It was then found to interact with the Coiled-Coil domain of the Rx and GPA2 resistance proteins, which confer resistance to Potato Virus X (PVX) and potato cyst nematode Globodera pallida, respectively. RanGAP2 is thought to mediate recognition of the avirulence protein GP-RBP-1 by GPA2. However, the Gpa2-induced hypersensitive response appears to be relatively weak and Gpa2 is limited in terms of spectrum of efficiency as it is effective against only two nematode populations. While functional and evolutionary analyses of Gp-Rbp-1 and Gpa2 identified key residues in both the resistance and avirulence proteins that are involved in recognition determination, whether variation in RanGAP2 also plays a role in pathogen recognition has not been investigated. We amplified a total of 147 RanGAP2 sequences from 55 accessions belonging to 18 different di-and tetraploid Solanum species from the section Petota. Among the newly identified sequences, 133 haplotypes were obtained and 19.1% of the nucleotide sites were found to be polymorphic. The observed intra-specific nucleotide diversity ranges from 0.1 to 1.3%. Analysis of the selection pressures acting on RanGAP2 suggests that this gene evolved mainly under purifying selection. Nonetheless, we identified polymorphic positions in the protein sequence at the intra-specific level, which could modulate the activity of RanGAP2. Two polymorphic sites and a three amino-acid deletion in RanGAP2 were found to affect the timing and intensity of the Gpa2-induced hypersensitive response to avirulent GP-RBP-1 variants even though they did not confer any gain of recognition of virulent GP-RBP-1 variants. Our results highlight how a resistance gene co-factor can manage in terms of evolution both an established role as a cell housekeeping gene and an implication in plant parasite interactions. StRanGAP2 gene

Assessment of anodal and cathodal transcranial direct current stimulation (tDCS) on MMN-indexed auditory sensory processing.

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Impey, Danielle; de la Salle, Sara; Knott, Verner

2016-06-01

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite (anodal stimulation) or inhibit (cathodal stimulation) activity in the brain area of interest via small electrodes placed on the scalp. Currently, tDCS of the frontal cortex is being used as a tool to investigate cognition in healthy controls and to improve symptoms in neurological and psychiatric patients. tDCS has been found to facilitate cognitive performance on measures of attention, memory, and frontal-executive functions. Recently, a short session of anodal tDCS over the temporal lobe has been shown to increase auditory sensory processing as indexed by the Mismatch Negativity (MMN) event-related potential (ERP). This preliminary pilot study examined the separate and interacting effects of both anodal and cathodal tDCS on MMN-indexed auditory pitch discrimination. In a randomized, double blind design, the MMN was assessed before (baseline) and after tDCS (2mA, 20min) in 2 separate sessions, one involving 'sham' stimulation (the device is turned off), followed by anodal stimulation (to temporarily excite cortical activity locally), and one involving cathodal stimulation (to temporarily decrease cortical activity locally), followed by anodal stimulation. Results demonstrated that anodal tDCS over the temporal cortex increased MMN-indexed auditory detection of pitch deviance, and while cathodal tDCS decreased auditory discrimination in baseline-stratified groups, subsequent anodal stimulation did not significantly alter MMN amplitudes. These findings strengthen the position that tDCS effects on cognition extend to the neural processing of sensory input and raise the possibility that this neuromodulatory technique may be useful for investigating sensory processing deficits in clinical populations. Copyright © 2016 Elsevier Inc. All rights reserved.

Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential.

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Carrion, Julio; Scisci, Elizabeth; Miles, Brodie; Sabino, Gregory J; Zeituni, Amir E; Gu, Ying; Bear, Adam; Genco, Caroline A; Brown, David L; Cutler, Christopher W

2012-09-15

The low-grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. In this study, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19(-)BDCA-1(+)DC-SIGN(+) blood myeloid DCs (mDCs) were analyzed in CP subjects with or without existing acute coronary syndrome and in healthy controls. FACS analysis revealed a significant increase in blood mDCs in the following order: healthy controls < CP < acute coronary syndrome/CP. Analysis of the blood mDC microbiome by 16S rDNA sequencing showed Porphyromonas gingivalis and other species, including (cultivable) Burkholderia cepacia. The mDC carriage rate with P. gingivalis correlated with oral carriage rate and with serologic exposure to P. gingivalis in CP subjects. Intervention (local debridement) to elicit a bacteremia increased the mDC carriage rate and frequency in vivo. In vitro studies established that P. gingivalis enhanced by 28% the differentiation of monocytes into immature mDCs; moreover, mDCs secreted high levels of matrix metalloproteinase-9 and upregulated C1q, heat shock protein 60, heat shock protein 70, CCR2, and CXCL16 transcripts in response to P. gingivalis in a fimbriae-dependent manner. Moreover, the survival of the anaerobe P. gingivalis under aerobic conditions was enhanced when within mDCs. Immunofluorescence analysis of oral mucosa and atherosclerotic plaques demonstrate infiltration with mDCs, colocalized with P. gingivalis. Our results suggest a role for blood mDCs in harboring and disseminating pathogens from oral mucosa to atherosclerosis plaques, which may provide key signals for mDC differentiation and atherogenic conversion.

Inter- and Intra-individual Variability in Response to Transcranial Direct Current Stimulation (tDCS) at Varying Current Intensities.

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Chew, Taariq; Ho, Kerrie-Anne; Loo, Colleen K

2015-01-01

Translation of transcranial direct current stimulation (tDCS) from research to clinical practice is hindered by a lack of consensus on optimal stimulation parameters, significant inter-individual variability in response, and in sufficient intra-individual reliability data. Inter-individual differences in response to anodal tDCS at a range of current intensities were explored. Intra-individual reliability in response to anodal tDCS across two identical sessions was also investigated. Twenty-nine subjects participated in a crossover study. Anodal-tDCS using four different current intensities (0.2, 0.5, 1 and 2 mA), with an anode size of 16 cm2, was tested. The 0.5 mA condition was repeated to assess intra-individual variability. TMS was used to elicit 40 motor-evoked potentials (MEPs) before 10 min of tDCS, and 20 MEPs at four time-points over 30 min following tDCS. ANOVA revealed no main effect of TIME for all conditions except the first 0.5 mA condition, and no differences in response between the four current intensities. Cluster analysis identified two clusters for the 0.2 and 2 mA conditions only. Frequency distributions based on individual subject responses (excitatory, inhibitory or no response) to each condition indicate possible differential responses between individuals to different current intensities. Test-retest reliability was negligible (ICC(2,1) = -0.50). Significant inter-individual variability in response to tDCS across a range of current intensities was found. 2 mA and 0.2 mA tDCS were most effective at inducing a distinct response. Significant intra-individual variability in response to tDCS was also found. This has implications for interpreting results of single-session tDCS experiments. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Enhancement of selective attention by tDCS: interaction with interference in a Sternberg task

NARCIS (Netherlands)

Gladwin, T.E.; den Uyl, T.E.; Fregni, F.F.; Wiers, R.W.

2012-01-01

Transcranial Direct Current Stimulation (tDCS) enhances performance on working memory tasks. However, such effects may be dependent on modulation of specific aspects of working memory. We therefore tested the hypothesis that tDCS improves selective attention in the context of a Sternberg task.

Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity.

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Orjon Rroji

Full Text Available Previous research suggests that anodal transcranial direct current stimulation (tDCS over the primary motor cortex (M1 modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements. Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP-like processes. Using a double-blind within-subject cross-over design, subjects (n=14 participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001 and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001. This effect was large (Cohen's d=1.01 and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.

Noninvasive transcranial direct current stimulation (tDCS) for the treatment of orofacial pain.

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Fricova, Jitka; Englerova, Katerina; Rokyta, Richard

2016-10-01

tDCS is a promising method for the treatment of chronic pain. Electrode placement locations must be chosen in accordance with the density and the time course of the current in order to prevent pathological changes in the underlying tissue. In order to reduce current spatial variability, more electrodes of the same polarity are placed in a circle around the second electrode of the opposite polarity. The applied current produced the greatest changes directly beneath the electrodes: the cathode reduces the excitability of cortical neurons, while the anode has the opposite effect. Based on inclusion criteria, 10 patients with chronic orofacial pain, secondary trigeminal neuralgia after oral surgery, were enrolled and underwent both anode and cathode stimulation. Before the first session we measured pain intensity on a numeric pain rating scale and tactile and thermal stimulation were used to assess somatosensory status. tDCS was applied for five consecutive days. At the end of tDCS application, somatosensory status was assessed again. From our results we can conclude that the application of tDCS improves the perception of some types of pain. When we increase our sample size, we would expect confirmation not only on our positive results, but also some additional findings for explaining the pathophysiology of orofacial pain. These pathophysiological findings and explanations are very important for the application of tDCS in the treatment of orofacial pain and also for other types of neuropathic pain.

Spelling rehabilitation using transcranial direct current (tDCS in primary progressive aphasia (PPA.

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Constantine Frangakis

2014-04-01

Full Text Available Introduction: Spelling impairments are one of the first deficits that occur early in PPA and can usually predict the variant of PPA in which the patient may progress (Sepelyak et al., 2011. PPA is a neurodegenerative disease that affects people relatively early in life (between 55-65 years and therefore it is important to find ways to alleviate the symptoms or impede the degree of degeneration. We present and discuss new data indicating that a neuromodulatory treatment, using transcranial direct current stimulation (tDCS combined with a spelling intervention, shows promise for maintaining or even improving language abilities in PPA. The aim of this research is to determine whether tDCS plus language therapy is more effective than language therapy alone in treating written language deficits in PPA. Methods: Eight PPA participants underwent anodal tDCS or sham plus spelling intervention in a randomized order using a within-subject cross-over design. They were evaluated before, after, and at 2 weeks and 2 months post-intervention. Spelling intervention varied for each participant according to the main spelling deficit: 3 patients had phoneme-to-grapheme conversion (PGC intervention, 2 had lexical intervention and 3 had advanced PGC intervention (combined with written fluency and PGC practice. Four more patients have already finished the first period of stimulations (ether sham or tDCS and all their other sessions and evaluations will be completed in the next couple months. Analyses-Results: We analyzed the existing set of full data using both within-subject analyses (McNemar tests and across-subjects analyses while taking into account carry-over effects. We evaluated therapy effects by the Generalized Estimating Equation approach (Liang & Zeger, 1986. All participants showed improvement in spelling after spelling intervention in trained items (with either sham or tDCS. There was, however, a significant improvement for untrained items only in the tDCS

Enhancing performance in numerical magnitude processing and mental arithmetic using transcranial Direct Current Stimulation (tDCS

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Tobias U. Hauser

2013-06-01

Full Text Available The ability to accurately process numerical magnitudes and solve mental arithmetic is of highest importance for schooling and professional career. Although impairments in these domains in disorders such as developmental dyscalculia (DD are highly detrimental, remediation is still sparse. In recent years, transcranial brain stimulation methods such as transcranial Direct Current Stimulation (tDCS have been suggested as a treatment for various neurologic and neuropsychiatric disorders. The posterior parietal cortex (PPC is known to be crucially involved in numerical magnitude processing and mental arithmetic. In this study, we evaluated whether tDCS has a beneficial effect on numerical magnitude processing and mental arithmetic. Due to the unclear lateralization, we stimulated the left, right as well as both hemispheres simultaneously in two experiments. We found that left anodal tDCS significantly enhanced performance in a number comparison and a subtraction task, while bilateral and right anodal tDCS did not induce any improvements compared to sham. Our findings demonstrate that the left PPC is causally involved in numerical magnitude processing and mental arithmetic. Furthermore, we show that these cognitive functions can be enhanced by means of tDCS. These findings encourage to further investigate the beneficial effect of tDCS in the domain of mathematics in healthy and impaired humans.

Two New Chroman Derivations from the Endophytic Penicillium sp. DCS523

OpenAIRE

Li, Jun-Tian; Fu, Xiao-Li; Tan, Chun; Zeng, Ying; Wang, Qi; Zhao, Pei-Ji

2011-01-01

Strain DCS523 was isolated from the branch tissue of Daphniphyllum longeracemosum and determined to be a Penicillium sp. according to the ITS sequence analysis. The extracts from the PDA solid fermentation media of Penicillium sp. DCS523 were purified to give two new chroman derivatives as well as six known compounds. Based on their spectral data the new compounds were identified as (Z)-6-acetyl- 3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (1) and 6-acetyl-2α,5- dihydroxy-2-(...

Cell death induced by GSM 900-MHz and DCS 1800-MHz mobile telephony radiation

International Nuclear Information System (INIS)

Panagopoulos, D. J; Chavdoula, E. D.; Nezis, I. P.; Margaritis, L. H.

2007-01-01

In the present study, the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay '' a well known technique widely used for detecting fragmented DNA in various types of cells'' was used to detect cell death (DNA fragmentation) in a biological model, the early and mid stages of oogenesis of the insect Drosophila melanogaster. The flies were exposed in vivo to either GSM 900-MHz (Global System for Mobile telecommunications) or DCS 1800-MHz (Digital Cellular System) radiation from a common digital mobile phone, for few minutes per day during the first 6 days of their adult life. The exposure conditions were similar to those to which a mobile phone user is exposed, and were determined according to previous studies of ours [D.J. Panagopoulos, A. Karabarbounis, L.H. Margaritis, Effect of GSM 900-MHz mobile phone radiation on the reproductive capacity of D. melanogaster, Electromagn. Biol. Med. 23 (1) (2004) 29''43; D.J. Panagopoulos, N. Messini, A. Karabarbounis, A.L. Philippetis, L.H. Margaritis, Radio frequency electromagnetic radiation within ''safety levels'' alters the physiological function of insects, in: P. Kostarakis, P. Stavroulakis (Eds.), Proceedings of the Millennium International Workshop on Biological Effects of Electromagnetic Fields, Heraklion, Crete, Greece, October 17''20, 2000, pp. 169''175, ISBN: 960-86733-0-5; D.J. Panagopoulos, L.H. Margaritis, Effects of electromagnetic fields on the reproductive capacity of D. melanogaster, in: P. Stavroulakis (Ed.), Biological Effects of Electromagnetic Fields, Springer, 2003, pp. 545''578], which had shown a large decrease in the oviposition of the same insect caused by GSM radiation. Our present results suggest that the decrease in oviposition previously reported, is due to degeneration of large numbers of egg chambers after DNA fragmentation of their constituent cells, induced by both types of mobile telephony radiation. Induced cell death is recorded for the first time, in all types of

Self-Administered Domiciliary tDCS Treatment for Tinnitus: A Double-Blind Sham-Controlled Study.

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Petteri Hyvärinen

Full Text Available Transcranial direct current stimulation (tDCS has shown potential for providing tinnitus relief, although positive effects have usually been observed only during a short time period after treatment. In recent studies the focus has turned from one-session experiments towards multi-session treatment studies investigating long-term outcomes with double-blinded and sham-controlled study designs. Traditionally, tDCS has been administered in a clinical setting by a healthcare professional but in studies involving multiple treatment sessions, often a trade-off has to be made between sample size and the amount of labor needed to run the trial. Also, as the number of required visits to the clinic increases, the dropout rate is likely to rise proportionally.The aim of the current study was to find out if tDCS treatment for tinnitus could be patient-administered in a domiciliary setting and whether the results would be comparable to those from in-hospital treatment studies. Forty-three patients with chronic (> 6 months tinnitus were involved in the study, and data on 35 out of these patients were included in final analysis. Patients received 20 minutes of left temporal area anodal (LTA or bifrontal tDCS stimulation (2 mA or sham stimulation (0.3 mA for ten consecutive days. An overall reduction in the main outcome measure, Tinnitus Handicap Inventory (THI, was found (mean change -5.0 points, p < 0.05, but there was no significant difference between active and sham treatment outcomes. Patients found the tDCS treatment easy to administer and they all tolerated it well. In conclusion, self-administered domiciliary tDCS treatment for tinnitus was found safe and feasible and gave outcome results similar to recent randomized controlled long-term treatment trials. The results suggest better overall treatment response-as measured by THI-with domiciliary treatment than with in-hospital treatment, but this advantage is not related to the tDCS variant. The study

Transcranial direct current stimulation (tDCS) neuromodulatory effects on mechanical hyperalgesia and cortical BDNF levels in ovariectomized rats.

Science.gov (United States)

da Silva Moreira, Sônia Fátima; Medeiros, Liciane Fernandes; de Souza, Andressa; de Oliveira, Carla; Scarabelot, Vanessa Leal; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-15

Epidemiological studies show that painful disorders are more prevalent in women than in men, and the transcranial direct current stimulation (tDCS) technique has been tested in chronic pain states. We explored the effect of tDCS on pain behavior and brain-derived neurotrophic factor (BDNF) levels in ovariectomized rats. Forty-five female Wistar adult rats were distributed into five groups: control (CT), ovariectomy + tDCS (OT), ovariectomy + sham tDCS (OS), sham ovariectomy + tDCS (ST), and sham ovariectomy+shamtDCS (SS). The rats were subjected to cathodal tDCS. The vaginal cytology and the estradiol levels confirmed the hormonal status. In addition, nociceptive behavior was evaluated using the tail-flick, von Frey, and hot-plate tests, as well as the BDNF levels in the serum, hypothalamus, hippocampus, spinal cord, and cerebral cortex. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical analysis, followed by the Bonferroni, and P-value b 0.05 was considered significant. The ovariectomized animals presented a hypersensitivity response in the hot-plate (P b 0.01) and von Frey (P b 0.05) tests, as well as increased serum BDNF (P b 0.05) and decreased hypothalamic BDNF (P b 0.01) levels. The OT, OS, ST, and SS groups showed decreased hippocampal BDNF levels as compared with the control group (P b 0.001). The interaction between tDCS and ovariectomy on the cortical BDNF levels (P b 0.01) was observed. The ovariectomy induced nociceptive hypersensitivity and altered serum and hypothalamic BDNF levels. The cathodal tDCS partially reversed nociceptive hypersensitivity.

Transcranial direct current stimulation (tDCS) facilitates overall visual search response times but does not interact with visual search task factors.

Science.gov (United States)

Sung, Kyongje; Gordon, Barry

2018-01-01

Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages.

Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

Science.gov (United States)

Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

2007-08-01

Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

Two new chroman derivations from the endophytic Penicillium sp. DCS523.

Science.gov (United States)

Li, Jun-Tian; Fu, Xiao-Li; Tan, Chun; Zeng, Ying; Wang, Qi; Zhao, Pei-Ji

2011-01-18

Strain DCS523 was isolated from the branch tissue of Daphniphyllum longeracemosum and determined to be a Penicillium sp. according to the ITS sequence analysis. The extracts from the PDA solid fermentation media of Penicillium sp. DCS523 were purified to give two new chroman derivatives as well as six known compounds. Based on their spectral data the new compounds were identified as (Z)-6-acetyl- 3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one and 6-acetyl-2α,5- dihydroxy-2-(2-hydroxypropyl)- 3α,8-dimethylchroman, respectively.

Hitachi's proposed DCS solution for new build CANDU EC6 using the G-HIACS unified platform

Energy Technology Data Exchange (ETDEWEB)

Tan, D.; Ishii, K.; Otsuka, Y.; Uemura, K., E-mail: daisuke.tan.ye@hitachi.com [Hitachi Ltd., Infrastructure Systems Co., Ibaraki (Japan); Marko, P.E. [Hitachi Power Systems Canada Ltd., Power and Industry Div., Ontario (Canada)

2013-07-01

Hitachi Ltd. has developed the safe and secure functional safety DCS controller for potential new build NPP projects in the global market. Hitachi has improved the availability, maintainability, and reliability for its latest DCS systems named G-HIACS. In this latest paper on its DCS product development program, Hitachi would like to report a proposed DCS solution for new build CANDU NSP and BOP based on the G-HIACS Unified Architecture (R800FS/HSC800FS vSAFE Functional Safety Controller and R900/HSC900 General Purpose Controller) hybrid control system. (author)

Test-retest reliability of prefrontal transcranial Direct Current Stimulation (tDCS) effects on functional MRI connectivity in healthy subjects.

Science.gov (United States)

Wörsching, Jana; Padberg, Frank; Helbich, Konstantin; Hasan, Alkomiet; Koch, Lena; Goerigk, Stephan; Stoecklein, Sophia; Ertl-Wagner, Birgit; Keeser, Daniel

2017-07-15

Transcranial Direct Current Stimulation (tDCS) of the prefrontal cortex (PFC) can be used for probing functional brain connectivity and meets general interest as novel therapeutic intervention in psychiatric and neurological disorders. Along with a more extensive use, it is important to understand the interplay between neural systems and stimulation protocols requiring basic methodological work. Here, we examined the test-retest (TRT) characteristics of tDCS-induced modulations in resting-state functional-connectivity MRI (RS fcMRI). Twenty healthy subjects received 20minutes of either active or sham tDCS of the dorsolateral PFC (2mA, anode over F3 and cathode over F4, international 10-20 system), preceded and ensued by a RS fcMRI (10minutes each). All subject underwent three tDCS sessions with one-week intervals in between. Effects of tDCS on RS fcMRI were determined at an individual as well as at a group level using both ROI-based and independent-component analyses (ICA). To evaluate the TRT reliability of individual active-tDCS and sham effects on RS fcMRI, voxel-wise intra-class correlation coefficients (ICC) of post-tDCS maps between testing sessions were calculated. For both approaches, results revealed low reliability of RS fcMRI after active tDCS (ICC (2,1) = -0.09 - 0.16). Reliability of RS fcMRI (baselines only) was low to moderate for ROI-derived (ICC (2,1) = 0.13 - 0.50) and low for ICA-derived connectivity (ICC (2,1) = 0.19 - 0.34). Thus, for ROI-based analyses, the distribution of voxel-wise ICC was shifted to lower TRT reliability after active, but not after sham tDCS, for which the distribution was similar to baseline. The intra-individual variation observed here resembles variability of tDCS effects in motor regions and may be one reason why in this study robust tDCS effects at a group level were missing. The data can be used for appropriately designing large scale studies investigating methodological issues such as sources of variability and

Discriminated benefits of a Mediterranean dietary pattern within a hypocaloric diet program on plasma RBP4 concentrations and other inflammatory markers in obese subjects.

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Hermsdorff, Helen Hermana Miranda; Zulet, M Ángeles; Abete, Itziar; Martínez, J Alfredo

2009-12-01

Personalized nutritional strategies to treat obesity may specifically influence inflammatory markers, in addition to reduce body weight. In the present study, we evaluated the effect of a hypocaloric diet based on a Mediterranean dietary pattern (MDP) on nutritional status as well as on plasma concentrations of retinol binding protein-4 (RBP4) and other proinflammatory markers. Fourty-one subjects (24F/17M; age: 37 ± 7 years; BMI: 32.2 ± 3.9 kg/m²) were assigned to follow a MDP within a caloric-restricted diet over an 8-week period. Anthropometrical, clinical, and biochemical variables were measured at baseline and endpoint after the nutritional program. Dietary intervention resulted in a mean weight loss of -4.4 ± 2.5 kg (P diet score from baseline was a significant and independent predictor factor for the decrease in plasma RBP4 concentration (P hypocaloric diet accompanying a high adherence to a MDP resulted in specific reductions on proinflammatory markers, in addition to a significant improvement in some metabolic syndrome features induced by weight loss, which could be a good combined strategy to treat obesity as well as related metabolic and inflammatory disorders.

Effects of transcranial direct current stimulation (tDCS) on multiscale complexity of dual-task postural control in older adults.

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Zhou, Diange; Zhou, Junhong; Chen, Hu; Manor, Brad; Lin, Jianhao; Zhang, Jue

2015-08-01

Transcranial direct current stimulation (tDCS) targeting the prefrontal cortex reduces the size and speed of standing postural sway in younger adults, particularly when performing a cognitive dual task. Here, we hypothesized that tDCS would alter the complex dynamics of postural sway as quantified by multiscale entropy (MSE). Twenty healthy older adults completed two study visits. Center-of-pressure (COP) fluctuations were recorded during single-task (i.e., quiet standing) and dual-task (i.e., standing while performing serial subtractions) conditions, both before and after a 20-min session of real or sham tDCS. MSE was used to estimate COP complexity within each condition. The percentage change in complexity from single- to dual-task conditions (i.e., dual-task cost) was also calculated. Before tDCS, COP complexity was lower (p = 0.04) in the dual-task condition as compared to the single-task condition. Neither real nor sham tDCS altered complexity in the single-task condition. As compared to sham tDCS, real tDCS increased complexity in the dual-task condition (p = 0.02) and induced a trend toward improved serial subtraction performance (p = 0.09). Moreover, those subjects with lower dual-task COP complexity at baseline exhibited greater percentage increases in complexity following real tDCS (R = -0.39, p = 0.05). Real tDCS also reduced the dual-task cost to complexity (p = 0.02), while sham stimulation had no effect. A single session of tDCS targeting the prefrontal cortex increased standing postural sway complexity with concurrent non-postural cognitive task. This form of noninvasive brain stimulation may be a safe strategy to acutely improve postural control by enhancing the system's capacity to adapt to stressors.

Consensus: "Can tDCS and TMS enhance motor learning and memory formation?"

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Reis, Janine; Robertson, Edwin; Krakauer, John W; Rothwell, John; Marshall, Lisa; Gerloff, Christian; Wassermann, Eric; Pascual-Leone, Alvaro; Hummel, Friedhelm; Celnik, Pablo A; Classen, Joseph; Floel, Agnes; Ziemann, Ulf; Paulus, Walter; Siebner, Hartwig R; Born, Jan; Cohen, Leonardo G

2008-10-01

Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this paper is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurological and psychiatric disorders.

Investigation of tDCS volume conduction effects in a highly realistic head model

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Wagner, S.; Rampersad, S. M.; Aydin, Ü.; Vorwerk, J.; Oostendorp, T. F.; Neuling, T.; Herrmann, C. S.; Stegeman, D. F.; Wolters, C. H.

2014-02-01

Objective. We investigate volume conduction effects in transcranial direct current stimulation (tDCS) and present a guideline for efficient and yet accurate volume conductor modeling in tDCS using our newly-developed finite element (FE) approach. Approach. We developed a new, accurate and fast isoparametric FE approach for high-resolution geometry-adapted hexahedral meshes and tissue anisotropy. To attain a deeper insight into tDCS, we performed computer simulations, starting with a homogenized three-compartment head model and extending this step by step to a six-compartment anisotropic model. Main results. We are able to demonstrate important tDCS effects. First, we find channeling effects of the skin, the skull spongiosa and the cerebrospinal fluid compartments. Second, current vectors tend to be oriented towards the closest higher conducting region. Third, anisotropic WM conductivity causes current flow in directions more parallel to the WM fiber tracts. Fourth, the highest cortical current magnitudes are not only found close to the stimulation sites. Fifth, the median brain current density decreases with increasing distance from the electrodes. Significance. Our results allow us to formulate a guideline for volume conductor modeling in tDCS. We recommend to accurately model the major tissues between the stimulating electrodes and the target areas, while for efficient yet accurate modeling, an exact representation of other tissues is less important. Because for the low-frequency regime in electrophysiology the quasi-static approach is justified, our results should also be valid for at least low-frequency (e.g., below 100 Hz) transcranial alternating current stimulation.

Towards unravelling reading-related modulations of tDCS-induced neuroplasticity in the human visual cortex

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Andrea eAntal

2014-06-01

Full Text Available Stimulation using weak electrical direct currents has shown to be capable of inducing polarity dependent diminutions or elevations in motor and visual cortical excitability. The aim of the present study was to test if reading during transcranial direct current stimulation (tDCS is able to modify stimulation-induced plasticity in the visual cortex. Phosphene thresholds (PT in 12 healthy subjects were recorded before and after 10 minutes of anodal, cathodal and sham tDCS in combination with reading. Reading alone decreased PTs significantly, compared to the sham tDCS condition without reading. Interestingly, after both anodal and cathodal stimulation there was a tendency toward smaller PTs. Our results support the observation that tDCS-induced plasticity is highly dependent on the cognitive state of the subject during stimulation, not only in the case of motor cortex but also in the case of visual cortex stimulation.

Finite element model predicts current density distribution for clinical applications of tDCS and tACS

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Toralf eNeuling

2012-09-01

Full Text Available Transcranial direct current stimulation (tDCS has been applied in numerous scientific studies over the past decade. However, the possibility to apply tDCS in therapy of neuropsychiatric disorders is still debated. While transcranial magnetic stimulation (TMS has been approved for treatment of major depression in the United States by the Food and Drug Administration (FDA, tDCS is not as widely accepted. One of the criticisms against tDCS is the lack of spatial specificity. Focality is limited by the electrode size (35 cm2 are commonly used and the bipolar arrangement. However, a current flow through the head directly from anode to cathode is an outdated view. Finite element (FE models have recently been used to predict the exact current flow during tDCS. These simulations have demonstrated that the current flow depends on tissue shape and conductivity. Toface the challenge to predict the location, magnitude and direction of the current flow induced by tDCS and transcranial alternating current stimulation (tACS, we used a refined realistic FE modeling approach. With respect to the literature on clinical tDCS and tACS, we analyzed two common setups for the location of the stimulation electrodes which target the frontal lobe and the occipital lobe, respectively. We compared lateral and medial electrode configuration with regard to theirusability. We were able to demonstrate that the lateral configurations yielded more focused stimulation areas as well as higher current intensities in the target areas. The high resolution of our simulation allows one to combine the modeled current flow with the knowledge of neuronal orientation to predict the consequences of tDCS and tACS. Our results not only offer a basis for a deeper understanding of the stimulation sites currently in use for clinical applications but also offer a better interpretation of observed effects.

tDCS for Memory Enhancement: Analysis of the Speculative Aspects of Ethical Issues.

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Voarino, Nathalie; Dubljević, Veljko; Racine, Eric

2016-01-01

Transcranial direct current stimulation (tDCS) is a promising technology to enhance cognitive and physical performance. One of the major areas of interest is the enhancement of memory function in healthy individuals. The early arrival of tDCS on the market for lifestyle uses and cognitive enhancement purposes lead to the voicing of some important ethical concerns, especially because, to date, there are no official guidelines or evaluation procedures to tackle these issues. The aim of this article is to review ethical issues related to uses of tDCS for memory enhancement found in the ethics and neuroscience literature and to evaluate how realistic and scientifically well-founded these concerns are? In order to evaluate how plausible or speculative each issue is, we applied the methodological framework described by Racine et al. (2014) for "informed and reflective" speculation in bioethics. This framework could be succinctly presented as requiring: (1) the explicit acknowledgment of factual assumptions and identification of the value attributed to them; (2) the validation of these assumptions with interdisciplinary literature; and (3) the adoption of a broad perspective to support more comprehensive reflection on normative issues. We identified four major considerations associated with the development of tDCS for memory enhancement: safety, autonomy, justice and authenticity. In order to assess the seriousness and likelihood of harm related to each of these concerns, we analyzed the assumptions underlying the ethical issues, and the level of evidence for each of them. We identified seven distinct assumptions: prevalence, social acceptance, efficacy, ideological stance (bioconservative vs. libertarian), potential for misuse, long term side effects, and the delivery of complete and clear information. We conclude that ethical discussion about memory enhancement via tDCS sometimes involves undue speculation, and closer attention to scientific and social facts would bring

Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS).

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Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

2016-09-01

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

75 FR 59686 - Proposed Information Collection; Comment Request; NOAA Space-Based Data Collection System (DCS...

Science.gov (United States)

2010-09-28

...., Washington, DC 20230 (or via the Internet at [email protected] ). FOR FURTHER INFORMATION CONTACT: Requests for... Environmental Satellite (GOES) DCS and the Polar-Orbiting Operational Environmental Satellite (POES) DCS, also... Collection Submittal include Internet, facsimile transmission and postal mailing of paper forms. III. Data...

In-vivo Imaging of Magnetic Fields Induced by Transcranial Direct Current Stimulation (tDCS) in Human Brain using MRI

Science.gov (United States)

Jog, Mayank V.; Smith, Robert X.; Jann, Kay; Dunn, Walter; Lafon, Belen; Truong, Dennis; Wu, Allan; Parra, Lucas; Bikson, Marom; Wang, Danny J. J.

2016-10-01

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that applies mA currents at the scalp to modulate cortical excitability. Here, we present a novel magnetic resonance imaging (MRI) technique, which detects magnetic fields induced by tDCS currents. This technique is based on Ampere’s law and exploits the linear relationship between direct current and induced magnetic fields. Following validation on a phantom with a known path of electric current and induced magnetic field, the proposed MRI technique was applied to a human limb (to demonstrate in-vivo feasibility using simple biological tissue) and human heads (to demonstrate feasibility in standard tDCS applications). The results show that the proposed technique detects tDCS induced magnetic fields as small as a nanotesla at millimeter spatial resolution. Through measurements of magnetic fields linearly proportional to the applied tDCS current, our approach opens a new avenue for direct in-vivo visualization of tDCS target engagement.

Effects of Transcranial Direct Current Stimulation (tDCS) on Human Memory.

Energy Technology Data Exchange (ETDEWEB)

Matzen, Laura E.; Trumbo, Michael Christopher Stefan

2014-10-01

Training a person in a new knowledge base or skill set is extremely time consuming and costly, particularly in highly specialized domains such as the military and the intelligence community. Recent research in cognitive neuroscience has suggested that a technique called transcranial direct current stimulation (tDCS) has the potential to revolutionize training by enabling learners to acquire new skills faster, more efficiently, and more robustly (Bullard et al., 2011). In this project, we tested the effects of tDCS on two types of memory performance that are critical for learning new skills: associative memory and working memory. Associative memory is memory for the relationship between two items or events. It forms the foundation of all episodic memories, so enhancing associative memory could provide substantial benefits to the speed and robustness of learning new information. We tested the effects of tDCS on associative memory, using a real-world associative memory task: remembering the links between faces and names. Working memory refers to the amount of information that can be held in mind and processed at one time, and it forms the basis for all higher-level cognitive processing. We investigated the degree of transfer between various working memory tasks (the N-back task as a measure of verbal working memory, the rotation-span task as a measure of visuospatial working memory, and Raven's progressive matrices as a measure of fluid intelligence) in order to determine if tDCS-induced facilitation of performance is task-specific or general.

At-Home Transcranial Direct Current Stimulation (tDCS With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms

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Alexa Riggs

2018-05-01

Full Text Available Transcranial direct current stimulation (tDCS delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications.Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support.Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS and a tDCS user survey.Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10–20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients’ training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and

At-Home Transcranial Direct Current Stimulation (tDCS) With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms.

Science.gov (United States)

Riggs, Alexa; Patel, Vaishali; Paneri, Bhaskar; Portenoy, Russell K; Bikson, Marom; Knotkova, Helena

2018-01-01

Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications. Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support. Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS) and a tDCS user survey. Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10-20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients' training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and there were no adverse

Influence of Anodal Transcranial Direct Current Stimulation (tDCS) over the Right Angular Gyrus on Brain Activity during Rest

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Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

2014-01-01

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site. PMID:24760013

Influence of anodal transcranial direct current stimulation (tDCS) over the right angular gyrus on brain activity during rest.

Science.gov (United States)

Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

2014-01-01

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.

Two New Chroman Derivations from the Endophytic Penicillium sp. DCS523

Directory of Open Access Journals (Sweden)

Qi Wang

2011-01-01

Full Text Available Strain DCS523 was isolated from the branch tissue of Daphniphyllum longeracemosum and determined to be a Penicillium sp. according to the ITS sequence analysis. The extracts from the PDA solid fermentation media of Penicillium sp. DCS523 were purified to give two new chroman derivatives as well as six known compounds. Based on their spectral data the new compounds were identified as (Z-6-acetyl- 3-(1,2-dihydroxypropylidene-5-hydroxy-8-methylchroman-2-one (1 and 6-acetyl-2α,5- dihydroxy-2-(2-hydroxypropyl- 3α,8-dimethylchroman (2, respectively.

Neural signature of tDCS, tPCS and their combination: Comparing the effects on neural plasticity

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Thibaut, Aurore; Russo, Cristina; Morales-Quezada, Leon; Hurtado-Puerto, Aura; Deitos, Alícia; Freedman, Steven; Carvalho, Sandra; Fregni, Felipe

2017-01-01

Transcranial pulsed current stimulation (tPCS) and transcranial direct current stimulation (tDCS) are two noninvasive neuromodulatory brain stimulation techniques whose effects on human brain and behavior have been studied individually. In the present study we aimed to quantify the effects of tDCS and tPCS, individually and in combination, on cortical activity, sensitivity and pain-related assessments in healthy individuals in order to understand their neurophysiological mechanisms and potential applications in clinical populations. A total of 48 healthy individuals participated in this randomized double blind sham controlled study. Participants were randomized to receive a single stimulation session of either: active or sham tPCS and active or sham tDCS. Quantitative electroencephalography (qEEG), sensitivity and pain assessments were used before and after each stimulation session. We observed that tPCS had a higher effect on power, as compared to tDCS, in several bandwidths on various cortical regions: the theta band in the parietal region (p = 0.021), the alpha band in the temporal (p = 0.009), parietal (p = 0.0063), and occipital (p tDCS significantly decreased power in the low beta bandwidth of the frontal (p = 0.0006), central (p = 0.0001), and occipital (p = 0.0003) regions, when compared to sham stimulation. Additionally, tDCS significantly increased power in high beta over the temporal (p = 0.0015) and parietal (p = 0.0007) regions, as compared to sham. We found no effect on sensitivity or pain-related assessments. We concluded that tPCS and tDCS have different neurophysiological mechanisms, elicit distinct signatures, and that the combination of the two leads to no effect or a decrease on qEEG power. Further studies are required to examine the effects of these techniques on clinical populations in which EEG signatures have been found altered. PMID:27765610

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

Science.gov (United States)

Santos-Pontelli, Taiza E G; Rimoli, Brunna P; Favoretto, Diandra B; Mazin, Suleimy C; Truong, Dennis Q; Leite, Joao P; Pontes-Neto, Octavio M; Babyar, Suzanne R; Reding, Michael; Bikson, Marom; Edwards, Dylan J

2016-01-01

Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.

Long-Term Effects of Repeated Prefrontal Cortex Transcranial Direct Current Stimulation (tDCS) on Food Craving in Normal and Overweight Young Adults.

Science.gov (United States)

Ljubisavljevic, M; Maxood, K; Bjekic, J; Oommen, J; Nagelkerke, N

The dorsolateral prefrontal cortex (DLPFC) plays an important role in the regulation of food intake. Several previous studies demonstrated that a single session of transcranial direct current stimulation (tDCS) of the DLPFC reduces food craving and caloric intake. We hypothesized that repeated tDCS of the right DLPFC cortex may exert long-term changes in food craving in young, healthy adults and that these changes may differ between normal and overweight subjects. Thirty healthy individuals who reported frequent food cravings without a prior history of eating disorders were initially recruited. Subjects were randomized into an ACTIVE group who received 5 days of real tDCS (20 minutes, anode right-cathode left montage, 2 mA with current density kept at 0.06 mA/cm2, 1 min ramp-up/ramp-down), and a SHAM group, who received one day of real tDCS, on the first day (same parameters), followed by 4 days of sham tDCS. Food craving intensity was examined by Food Craving Questionnaires State and Trait and Food Craving Inventory before, during, (5-days) and one month (30-days) after tDCS. Single session of tDCS significantly reduced the intensity of current food craving (FCQ-S). Five days of active tDCS significantly reduced habitual experiences of food craving (FCQ-T), when compared to baseline pre-stimulation levels. Furthermore, both current (FCQ-S) and habitual craving (FCQ-T) were significantly reduced 30 days after active tDCS, while sham tDCS, i.e. a single tDCS session did not have significant effects. Also, active tDCS significantly decreased craving for fast food and sweets, and to a lesser degree for fat, while it did not have significant effects on craving for carbohydrates (FCI). There were no significant differences between individual FCQ-T subscales (craving dimensions) after 5 or 30 days of either sham or active tDCS. Changes in craving were not significantly associated with the initial weight, or with weight changes 30 days after the stimulation in the

DCS-SVM: a novel semi-automated method for human brain MR image segmentation.

Science.gov (United States)

Ahmadvand, Ali; Daliri, Mohammad Reza; Hajiali, Mohammadtaghi

2017-11-27

In this paper, a novel method is proposed which appropriately segments magnetic resonance (MR) brain images into three main tissues. This paper proposes an extension of our previous work in which we suggested a combination of multiple classifiers (CMC)-based methods named dynamic classifier selection-dynamic local training local Tanimoto index (DCS-DLTLTI) for MR brain image segmentation into three main cerebral tissues. This idea is used here and a novel method is developed that tries to use more complex and accurate classifiers like support vector machine (SVM) in the ensemble. This work is challenging because the CMC-based methods are time consuming, especially on huge datasets like three-dimensional (3D) brain MR images. Moreover, SVM is a powerful method that is used for modeling datasets with complex feature space, but it also has huge computational cost for big datasets, especially those with strong interclass variability problems and with more than two classes such as 3D brain images; therefore, we cannot use SVM in DCS-DLTLTI. Therefore, we propose a novel approach named "DCS-SVM" to use SVM in DCS-DLTLTI to improve the accuracy of segmentation results. The proposed method is applied on well-known datasets of the Internet Brain Segmentation Repository (IBSR) and promising results are obtained.

Electrodes for high-definition transcutaneous DC stimulation for applications in drug-delivery and electrotherapy, including tDCS

OpenAIRE

Minhas, Preet; Bansal, Varun; Patel, Jinal; Ho, Johnson S.; Diaz, Julian; Datta, Abhishek; Bikson, Marom

2010-01-01

Transcutaneous electrical stimulation is applied in a range of biomedical applications including Transcranial Direct Current Stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (

Changes in corticomotor excitability and intracortical inhibition of the primary motor cortex forearm area induced by anodal tDCS.

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Xue Zhang

Full Text Available OBJECTIVE: Previous studies have investigated how tDCS over the primary motor cortex modulates excitability in the intrinsic hand muscles. Here, we tested if tDCS changes corticomotor excitability and/or cortical inhibition when measured in the extensor carpi radialis (ECR and if these aftereffects can be successfully assessed during controlled muscle contraction. METHODS: We implemented a double blind cross-over design in which participants (n = 16 completed two sessions where the aftereffects of 20 min of 1 mA (0.04 mA/cm2 anodal vs sham tDCS were tested in a resting muscle, and two more sessions where the aftereffects of anodal vs sham tDCS were tested in an active muscle. RESULTS: Anodal tDCS increased corticomotor excitability in ECR when aftereffects were measured with a low-level controlled muscle contraction. Furthermore, anodal tDCS decreased short interval intracortical inhibition but only when measured at rest and after non-responders (n = 2 were removed. We found no changes in the cortical silent period. CONCLUSION: These findings suggest that targeting more proximal muscles in the upper limb with anodal tDCS is achievable and corticomotor excitability can be assessed in the presence of a low-level controlled contraction of the target muscle.

No Effects of Stimulating the Left Ventrolateral Prefrontal Cortex with tDCS on Verbal Working Memory Updating

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Karolina M. Lukasik

2018-01-01

Full Text Available The effects of transcranial direct current stimulation (tDCS on dorsolateral prefrontal cortex functions, such as working memory (WM, have been examined in a number of studies. However, much less is known about the behavioral effects of tDCS over other important WM-related brain regions, such as the ventrolateral prefrontal cortex (VLPFC. In a counterbalanced within-subjects design with 33 young healthy participants, we examined whether online and offline single-session tDCS over VLPFC affects WM updating performance as measured by a digit 3-back task. We compared three conditions: anodal, cathodal and sham. We observed no significant tDCS effects on participants' accuracy or reaction times during or after the stimulation. Neither did we find any differences between anodal and cathodal stimulation. Largely similar results were obtained when comparing subgroups of high- and low-performing participants. Possible reasons for the lack of effects, including individual differences in responsiveness to tDCS, features of montage, task and sample characteristics, and the role of VLPFC in WM, are discussed.

Wearable functional Near Infrared Spectroscopy (fNIRS and transcranial Direct Current Stimulation (tDCS: Expanding Vistas for Neurocognitive Augmentation

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Ryan eMcKendrick

2015-03-01

Full Text Available Contemporary studies with transcranial direct current stimulation (tDCS provide a growing base of evidence for enhancing cognition through the non-invasive delivery of weak electric currents to the brain. The main effect of tDCS is to modulate cortical excitability depending on the polarity of the applied current. However, the underlying mechanism of neuromodulation is not well understood. A new generation of functional near infrared spectroscopy (fNIRS systems is described that are miniaturized, portable, and include wearable sensors. These developments provide an opportunity to couple fNIRS with tDCS, consistent with a neuroergonomics approach for joint neuroimaging and neurostimulation investigations of cognition in complex tasks and in naturalistic conditions. The effects of tDCS on complex task performance and the use of fNIRS for monitoring cognitive workload during task performance are described. Also explained is how fNIRS + tDCS can be used simultaneously for assessing spatial working memory. Mobile optical brain imaging is a promising neuroimaging tool that has the potential to complement tDCS for realistic applications in natural settings.

Transcranial direct current stimulation (tDCS) to improve naming ability in post-stroke aphasia: A critical review.

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ALHarbi, Mohammed F; Armijo-Olivo, Susan; Kim, Esther S

2017-08-14

Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation tool that can be used to influence cortical brain activity to induce measurable behavioral changes. Although there is growing evidence that tDCS combined with behavioural language therapy could boost language recovery in patients with post-stroke aphasia, there is great variability in patient characteristics, treatment protocols, and outcome measures in these studies that poses challenges for analyzing the evidence. The purpose of this study is to critically analyze the methodological rigor of the evidence regarding the use of tDCS for post-stroke anomia. This critical review was conducted by searching four databases (MEDLINE, EMBase, PsycINFO, and CINAHL). Nineteen studies fully met the inclusion criteria. Three critical appraisal tools and Robey and Schultz's (1998) five- phase model for conducting clinical outcome research were adopted to evaluate and analyze the current level of evidence. Methodological issues of the studies were also identified. The current level of evidence for using tDCS for anomia is at the pre-efficacy level with emerging evidence at the efficacy level. Lack of proper evaluation of carry-over effects in cross-over studies, lack of or unclear randomization, allocation concealment, and incomplete data handling were the main methodological issues that could threaten the validity of the tDCS for anomia studies. Several methodological issues have been identified in pre-efficacy studies that pose challenges in determining whether tDCS is a beneficial adjunct to behavioral aphasia therapy. Future studies need to improve the quality of the methods used to investigate the effect of tDCS for anomia. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of phenotypic and functional maturation of murine dendritic cells (DCs) by purified Achyranthes bidentata polysaccharide (ABP).

Science.gov (United States)

Zou, Yaxuan; Meng, Jingjuan; Chen, Wenna; Liu, Jingling; Li, Xuan; Li, Weiwei; Lu, Changlong; Shan, Fengping

2011-08-01

There are a large number of interactions at molecular and cellular levels between the plant polysaccharides and immune system. Plant polysaccharides present an interesting effects as immunomodulators, particularly in the induction of the cells both in innate and adaptive immune systems. Activation of DCs could improve antitumoral responses usually diminished in cancer patients, and natural adjuvants provide a possibility of inducing this activation. ABP is a purified polysaccharide isolated from Achyranthes bidentata, a traditional Chinese medicine (TCM). The aim of this study is to investigate modulation of phenotypic and functional maturation of murine DCs by ABP. Both phenotypic and functional activities were assessed with use of conventional scanning electronic microscopy (SEM) for the morphology of the DC, transmitted electron microscopy (TEM) for intracellular lysosomes inside the DC, cellular immunohistochemistry for phagocytosis by the DCs, flow cytometry (FCM) for the changes in key surface molecules, bio-assay for the activity of acidic phosphatases (ACP), and ELISA for the production of pro-inflammatory cytokine IL-12. In fact, we found that purified ABP induced phenotypic maturation revealed by increased expression of CD86, CD40, and MHC II. Functional experiments showed the down-regulation of ACP inside DCs (which occurs when phagocytosis of DCs is decreased, and antigen presentation increased with maturation). Finally, ABP increased the production of IL-12. These data reveal that ABP promotes effective activation of murine DCs. This adjuvant-like activity may have therapeutic applications in clinical settings where immune responses need boosting. It is therefore concluded that ABP can exert positive modulation to murine DCs. Copyright © 2011 Elsevier B.V. All rights reserved.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel

Science.gov (United States)

Fregni, F; Nitsche, MA; Loo, C.K.; Brunoni, AR; Marangolo, P; Leite, J; Carvalho, S; Bolognini, N; Caumo, W; Paik, NJ; Simis, M; Ueda, K; Ekhitari, H; Luu, P; Tucker, DM; Tyler, WJ; Brunelin, J; Datta, A; Juan, CH; Venkatasubramanian, G; Boggio, PS; Bikson, M

2014-01-01

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. PMID:25983531

Effects of Transcranial Direct Current Stimulation (tDCS) on Behaviour and Electrophysiology of Language Production

Science.gov (United States)

Wirth, Miranka; Rahman, Rasha Abdel; Kuenecke, Janina; Koenig, Thomas; Horn, Helge; Sommer, Werner; Dierks, Thomas

2011-01-01

Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left…

Different populations of CD11b⁺ dendritic cells drive Th2 responses in the small intestine and colon

DEFF Research Database (Denmark)

Mayer, Johannes U.; Demiri, Mimoza; Agace, William Winston

2017-01-01

and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively...... prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+ CD103+ DCs induce Th2 responses in the small...

No Effects of Bilateral tDCS over Inferior Frontal Gyrus on Response Inhibition and Aggression.

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Franziska Dambacher

Full Text Available Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses to the right and approach motivation (relevant for aggressive actions to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS to the inferior frontal cortex. In one group we induced right-hemispheric fronto-cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT and aggression with the Taylor Aggression Paradigm (TAP. We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of tDCS

A distinct dendritic cell population arises in the thymus of IL-13Rα1-sufficient but not IL-13Rα1-deficient mice.

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Barik, Subhasis; Miller, Mindy; Cattin-Roy, Alexis; Ukah, Tobechukwu; Zaghouani, Habib

2018-06-18

IL-13 receptor alpha 1 (IL-13Rα1) associates with IL-4Rα to form a functional IL-4Rα/IL-13Rα1 heteroreceptor (HR) through which both IL-4 and IL-13 signal. Recently, HR expression was associated with the development of M2 type macrophages which function as antigen presenting cells (APCs). Herein, we show that a subset of thymic resident dendritic cells (DCs) expressing high CD11b (CD11b hi ) and intermediate CD11c (CD11c int ) arise in HR-sufficient but not HR-deficient mice. These DCs, which originate from the bone marrow are able to take up Ag from the peritoneum, traffic through the spleen and the lymph nodes and carry it to the thymus. In addition, since the DCs are able to present Ag to T cells, express high levels of the costimulatory molecule CD24, and comprise a CD8α + subset, it is likely that the cells contribute to T cell development and perhaps negative selection of self-reactive lymphocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Failure of the straight-line DCS boundary when extrapolated to the hypobaric realm.

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Conkin, J; Van Liew, H D

1992-11-01

The lowest pressure (P2) to which a diver can ascend without developing decompression sickness (DCS) after becoming equilibrated at some higher pressure (P1) is described by a straight line with a negative y-intercept. We tested whether extrapolation of such a line also predicts safe decompression to altitude. We substituted tissue nitrogen pressure (P1N2) calculated for a compartment with a 360-min half-time for P1 values; this allows data from hypobaric exposures to be plotted on a P2 vs. P1N2 graph, even if the subject breathes oxygen before ascent. In literature sources, we found 40 reports of human exposures in hypobaric chambers that fell in the region of a P2 vs. P1N2 plot where the extrapolation from hyperbaric data predicted that the decompression should be free of DCS. Of 4,576 exposures, 785 persons suffered decompression sickness (17%), indicating that extrapolation of the diver line to altitude is not valid. Over the pressure range spanned by human hypobaric exposures and hyperbaric air exposures, the best separation between no DCS and DCS on a P2 vs. P1N2 plot seems to be a curve which approximates a straight line in the hyperbaric region but bends toward the origin in the hypobaric region.

The effectiveness of ground level post-flight 100 percent oxygen breathing as therapy for pain-only altitude Decompression Sickness (DCS)

Science.gov (United States)

Demboski, John T.; Pilmanis, Andrew A.

1994-01-01

In both the aviation and space environments, decompression sickness (DCS) is an operational limitation. Hyperbaric recompression is the most efficacious treatment for altitude DCS. However, the inherent recompression of descent to ground level while breathing oxygen is in itself therapy for altitude DCS. If pain-only DCS occurs during a hypobaric exposure, and the symptoms resolver during descent, ground level post-flight breathing of 100% O2 for 2 hours (GLO2) is considered sufficient treatment by USAF Regulation 161-21. The effectiveness of the GLO2 treatment protocol is defined.

Use of Computational Modeling to Inform tDCS Electrode Montages for the Promotion of Language Recovery in Post-stroke Aphasia.

Science.gov (United States)

Galletta, Elizabeth E; Cancelli, Andrea; Cottone, Carlo; Simonelli, Ilaria; Tecchio, Franca; Bikson, Marom; Marangolo, Paola

2015-01-01

Although pilot trials of transcranial direct current stimulation (tDCS) in aphasia are encouraging, protocol optimization is needed. Notably, it has not yet been clarified which of the varied electrode montages investigated is the most effective in enhancing language recovery. To consider and contrast the predicted brain current flow patterns (electric field distribution) produced by varied 1×1 tDCS (1 anode, 1 cathode, 5 × 7 cm pad electrodes) montages used in aphasia clinical trials. A finite element model of the head of a single left frontal stroke patient was developed in order to study the pattern of the cortical EF magnitude and inward/outward radial EF under five different electrode montages: Anodal-tDCS (A-tDCS) over the left Wernicke's area (Montage A) and over the left Broca's area (Montage B); Cathodal tDCS (C-tDCS) over the right homologue of Wernicke's area (Montage C), and of Broca's area (Montage D), where for all montages A-D the "return" electrode was placed over the supraorbital contralateral forehead; bilateral stimulation with A-tDCS over the left Broca's and CtDCS over the right Broca's homologue (Montage E). In all cases, the "return" electrode over the contralesional supraorbital forehead was not inert and influenced the current path through the entire brain. Montage B, although similar to montage D in focusing the current in the perilesional area, exerted the greatest effect over the left perilesional cortex, which was even stronger in montage E. The position and influence of both electrodes must be considered in the design and interpretation of tDCS clinical trials for aphasia. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers.

Science.gov (United States)

Mariano, Timothy Y; Van't Wout, Mascha; Garnaat, Sarah L; Rasmussen, Steven A; Greenberg, Benjamin D

2016-04-01

Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed. © 2015

Determination of optimal electrode positions for transcranial direct current stimulation (tDCS)

International Nuclear Information System (INIS)

Im, Chang-Hwan; Jung, Hui-Hun; Choi, Jung-Do; Lee, Soo Yeol; Jung, Ki-Young

2008-01-01

The present study introduces a new approach to determining optimal electrode positions in transcranial direct current stimulation (tDCS). Electric field and 3D conduction current density were analyzed using 3D finite element method (FEM) formulated for a dc conduction problem. The electrode positions for minimal current injection were optimized by changing the Cartesian coordinate system into the spherical coordinate system and applying the (2+6) evolution strategy (ES) algorithm. Preliminary simulation studies applied to a standard three-layer head model demonstrated that the proposed approach is promising in enhancing the performance of tDCS. (note)

Determination of optimal electrode positions for transcranial direct current stimulation (tDCS)

Energy Technology Data Exchange (ETDEWEB)

Im, Chang-Hwan; Jung, Hui-Hun; Choi, Jung-Do [Department of Biomedical Engineering, Yonsei University, Wonju, 220-710 (Korea, Republic of); Lee, Soo Yeol [Department of Biomedical Engineering, Kyung Hee University, Suwon (Korea, Republic of); Jung, Ki-Young [Korea University Medical Center, Korea University College of Medicine, Seoul (Korea, Republic of)], E-mail: ich@yonsei.ac.kr

2008-06-07

The present study introduces a new approach to determining optimal electrode positions in transcranial direct current stimulation (tDCS). Electric field and 3D conduction current density were analyzed using 3D finite element method (FEM) formulated for a dc conduction problem. The electrode positions for minimal current injection were optimized by changing the Cartesian coordinate system into the spherical coordinate system and applying the (2+6) evolution strategy (ES) algorithm. Preliminary simulation studies applied to a standard three-layer head model demonstrated that the proposed approach is promising in enhancing the performance of tDCS. (note)

Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS.

Directory of Open Access Journals (Sweden)

Christian Plewnia

Full Text Available Cognitive control (CC of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.

Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS).

Science.gov (United States)

Plewnia, Christian; Schroeder, Philipp A; Kunze, Roland; Faehling, Florian; Wolkenstein, Larissa

2015-01-01

Cognitive control (CC) of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS) has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC) can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT) that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.

High Definition Transcranial Direct Current Stimulation Induces Both Acute and Persistent Changes in Broadband Cortical Synchronization: a Simultaneous tDCS-EEG Study

Science.gov (United States)

Roy, Abhrajeet; Baxter, Bryan

2014-01-01

The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high definition transcranial direct current stimulation (tDCS) using high resolution electroencephalography (EEG). Previous studies have pointed to the after effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event related synchronization (ERS) were observed during and after the application of high definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of 8 subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event related desynchronization (ERD) and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high resolution EEG during high definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration. PMID:24956615

Computational Pipeline for NIRS-EEG Joint Imaging of tDCS-Evoked Cerebral Responses-An Application in Ischemic Stroke.

Science.gov (United States)

Guhathakurta, Debarpan; Dutta, Anirban

2016-01-01

Transcranial direct current stimulation (tDCS) modulates cortical neural activity and hemodynamics. Electrophysiological methods (electroencephalography-EEG) measure neural activity while optical methods (near-infrared spectroscopy-NIRS) measure hemodynamics coupled through neurovascular coupling (NVC). Assessment of NVC requires development of NIRS-EEG joint-imaging sensor montages that are sensitive to the tDCS affected brain areas. In this methods paper, we present a software pipeline incorporating freely available software tools that can be used to target vascular territories with tDCS and develop a NIRS-EEG probe for joint imaging of tDCS-evoked responses. We apply this software pipeline to target primarily the outer convexity of the brain territory (superficial divisions) of the middle cerebral artery (MCA). We then present a computational method based on Empirical Mode Decomposition of NIRS and EEG time series into a set of intrinsic mode functions (IMFs), and then perform a cross-correlation analysis on those IMFs from NIRS and EEG signals to model NVC at the lesional and contralesional hemispheres of an ischemic stroke patient. For the contralesional hemisphere, a strong positive correlation between IMFs of regional cerebral hemoglobin oxygen saturation and the log-transformed mean-power time-series of IMFs for EEG with a lag of about -15 s was found after a cumulative 550 s stimulation of anodal tDCS. It is postulated that system identification, for example using a continuous-time autoregressive model, of this coupling relation under tDCS perturbation may provide spatiotemporal discriminatory features for the identification of ischemia. Furthermore, portable NIRS-EEG joint imaging can be incorporated into brain computer interfaces to monitor tDCS-facilitated neurointervention as well as cortical reorganization.

Task-specificity of unilateral anodal and dual-M1 tDCS effects on motor learning.

Science.gov (United States)

Karok, Sophia; Fletcher, David; Witney, Alice G

2017-01-08

Task-specific effects of transcranial direct current stimulation (tDCS) on motor learning were investigated in 30 healthy participants. In a sham-controlled, mixed design, participants trained on 3 different motor tasks (Purdue Pegboard Test, Visuomotor Grip Force Tracking Task and Visuomotor Wrist Rotation Speed Control Task) over 3 consecutive days while receiving either unilateral anodal over the right primary motor cortex (M1), dual-M1 or sham stimulation. Retention sessions were administered 7 and 28 days after the end of training. In the Purdue Pegboard Test, both anodal and dual-M1 stimulation reduced average completion time approximately equally, an improvement driven by online learning effects and maintained for about 1 week. The Visuomotor Grip Force Tracking Task and the Visuomotor Wrist Rotation Speed Control Task were associated with an advantage of dual-M1 tDCS in consolidation processes both between training sessions and when testing at long-term retention; both were maintained for at least 1 month. This study demonstrates that M1-tDCS enhances and sustains motor learning with different electrode montages. Stimulation-induced effects emerged at different learning phases across the tasks, which strongly suggests that the influence of tDCS on motor learning is dynamic with respect to the functional recruitment of the distributed motor system at the time of stimulation. Divergent findings regarding M1-tDCS effects on motor learning may partially be ascribed to task-specific consequences and the effects of offline consolidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-term effects of serial anodal tDCS on motion perception in subjects with occipital stroke measured in the unaffected visual hemifield

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Manuel C Olma

2013-06-01

Full Text Available Transcranial direct current stimulation (tDCS is a novel neuromodulatory tool that has seen early transition to clinical trials, although the high variability of these findings necessitates further studies in clincally-relevant populations. The majority of evidence into effects of repeated tDCS is based on research in the human motor system, but it is unclear whether the long-term effects of serial tDCS are motor-specific or transferable to other brain areas. This study aimed to examine whether serial anodal tDCS over the visual cortex can exogenously induce long-term neuroplastic changes in the visual cortex. However, when the visual cortex is affected by a cortical lesion, up-regulated endogenous neuroplastic adaptation processes may alter the susceptibility to tDCS. To this end, motion perception was investigated in the unaffected hemifield of subjects with unilateral visual cortex lesions. Twelve subjects with occipital ischaemic lesions participated in a within-subject, sham-controlled, double-blind study. MRI-registered sham or anodal tDCS (1.5 mA, 20 minutes was applied on five consecutive days over the visual cortex. Motion perception was tested before and after stimulation sessions and at 14- and 28-day follow-up. After a 16-day interval an identical study block with the other stimulation condition (anodal or sham tDCS followed. Serial anodal tDCS over the visual cortex resulted in an improvement in motion perception, a function attributed to MT/V5. This effect was still measurable at 14- and 28-day follow-up measurements. Thus, this may represent evidence for long-term tDCS-induced plasticity and has implications for the design of studies examining the time course of tDCS effects in both the visual and motor systems.

STAMP model and its application prospect in DCS safety analysis of nuclear power plant

International Nuclear Information System (INIS)

Yang Xiaohua; Liu Jie; Liu Zhaohui; Liu Hua; Yu Tonglan

2013-01-01

The application of DCS (Digit Control System) is a certain trend for the development of nuclear power. DCS not only improves the control capability of nuclear power system, but also increases the complexity of the system. Traditional safety analysis techniques based on event-chain model are facing challenges. In order to improve the safety performance of nuclear power DCS, the latest research achievement in the field of safety engineering should be focused, studied and applied into nuclear power safety. This paper introduces a new safety analysis model named STAMP (Systems-Theoretic Accident Modeling and Processes) based on the system theory, analyzes its advantages and disadvantages compared with the traditional ones, and explains the basic steps of STPA (STAMP-Based Hazard Analysis) technology. Finally, according to the application status of STAMP at home and abroad, it prospects the development of STAMP in China's nuclear power safety. (authors)

Modelling the effect of electrode displacement on transcranial direct current stimulation (tDCS)

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Ramaraju, Sriharsha; Roula, Mohammed A.; McCarthy, Peter W.

2018-02-01

Objective. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers a low-intensity, direct current to cortical areas with the purpose of modulating underlying brain activity. Recent studies have reported inconsistencies in tDCS outcomes. The underlying assumption of many tDCS studies has been that replication of electrode montage equates to replicating stimulation conditions. It is possible however that anatomical difference between subjects, as well as inherent inaccuracies in montage placement, could affect current flow to targeted areas. The hypothesis that stimulation of a defined brain region will be stable under small displacements was tested. Approach. Initially, we compared the total simulated current flowing through ten specific brain areas for four commonly used tDCS montages: F3-Fp2, C3-Fp2, Fp1-F4, and P3-P4 using the software tool COMETS. The effect of a slight (~1 cm in each of four directions) anode displacement on the simulated regional current density for each of the four tDCS montages was then determined. Current flow was calculated and compared through ten segmented brain areas to determine the effect of montage type and displacement. The regional currents, as well as the localised current densities, were compared with the original electrode location, for each of these new positions. Main results. Recommendations for montages that maximise stimulation current for the ten brain regions are considered. We noted that the extent to which stimulation is affected by electrode displacement varies depending on both area and montage type. The F3-Fp2 montage was found to be the least stable with up to 38% change in average current density in the left frontal lobe while the Fp1-F4 montage was found to the most stable exhibiting only 1% change when electrodes were displaced. Significance. These results indicate that even relatively small changes in stimulation electrode placement appear to result in surprisingly large

Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance.

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Hoseini, Najmeh; Munoz-Rubke, Felipe; Wan, Hsuan-Yu; Block, Hannah J

2016-10-28

Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders.

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Kekic, Maria; Boysen, Elena; Campbell, Iain C; Schmidt, Ulrike

2016-03-01

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique, which can be used to selectively disrupt patterns of neural activity that are associated with symptoms of mental illness. tDCS has been implemented in numerous therapeutic trials across a range of patient populations, with a rapidly increasing number of studies being published each year. This systematic review aimed to evaluate the efficacy of tDCS in the treatment of psychiatric disorders. Four electronic databases were searched from inception until December 2015 by two independent reviewers, and 66 eligible studies were identified. Depression was the most extensively researched condition, followed by schizophrenia and substance use disorders. Data on obsessive compulsive disorder, generalised anxiety disorder, and anorexia nervosa were also obtained. The quality of included studies was appraised using a standardised assessment framework, which yielded a median score corresponding to "weak" on the three-point scale. This improved to "moderate" when case reports/series were excluded from the analysis. Overall, data suggested that tDCS interventions comprising multiple sessions can ameliorate symptoms of several major psychiatric disorders, both acutely and in the long-term. Nevertheless, the tDCS field is still in its infancy, and several methodological and ethical issues must be addressed before clinical efficacy can truly be determined. Studies probing the mechanisms of action of tDCS and those facilitating the definition of optimised stimulation protocols are warranted. Furthermore, evidence from large-scale, multi-centre randomised controlled trials is required if the transition of this therapy from the laboratory to the clinic is to be considered. Copyright © 2015 Elsevier Ltd. All rights reserved.

Testing the involvement of the prefrontal cortex in lucid dreaming: a tDCS study.

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Stumbrys, Tadas; Erlacher, Daniel; Schredl, Michael

2013-12-01

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.

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Elsner, Bernhard; Kwakkel, Gert; Kugler, Joachim; Mehrholz, Jan

2017-09-13

Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. CRD42016042055. We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Transcranial direct current stimulation (tDCS in behavioral and food addiction: A systematic review of efficacy, technical and methodological issues

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Anne eSauvaget

2015-10-01

Full Text Available Objectives.Behavioral addictions (BA are complex disorders for which pharmacological and psychotherapeutic treatments have shown their limits. Non-invasive brain stimulation, among which transcranial direct current stimulation (tDCS, has opened up new perspectives in addiction treatment. The purpose of this work is to conduct a critical and systematic review of tDCS efficacy, and of technical and methodological considerations in the field of BA.Methods.A bibliographic search has been conducted on the Medline and ScienceDirect databases until December 2014, based on the following selection criteria: clinical studies on tDCS and BA (namely eating disorders, compulsive buying, Internet addiction, pathological gambling, sexual addiction, sports addiction, video games addiction. Study selection, data analysis and reporting were conducted according to the PRISMA guidelines.Results.Out of 402 potential articles, seven studies were selected. So far focusing essentially on abnormal eating, these studies suggest that tDCS (right prefrontal anode / left prefrontal cathode reduces food craving induced by visual stimuli.ConclusionsDespite methodological and technical differences between studies, the results are promising. So far, only few studies of tDCS in BA have been conducted. New research is recommended on the use of tDCS in BA, other than eating disorders.

Research of quality control during development of NPP DCS 1E classified software

International Nuclear Information System (INIS)

Shi Weihua; Lu Zhenguo; Xie Qi

2012-01-01

The Nuclear safety depends on right behavior of 1E software, which is a important part of 1E DCS system. Nowadays, user focus on good function of 1E system, but pay little attention to quality control of 1E software. In fact, it's declared in IEC61513 and IEC60880 that 1E software should under strict quality control during all stages of development. This article is related to the practice of 1E DCS system quality control and explores the QC surveillance for 1E software from the user's point of view. (authors)

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

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Filho, Paulo Ricardo Marques; Vercelino, Rafael; Cioato, Stefania Giotti; Medeiros, Liciane Fernandes; de Oliveira, Carla; Scarabelot, Vanessa Leal; Souza, Andressa; Rozisky, Joanna Ripoll; Quevedo, Alexandre da Silva; Adachi, Lauren Naomi Spezia; Sanches, Paulo Roberto S; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-04

Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, PtDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, PtDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, PtDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels

No evidential value in samples of transcranial direct current stimulation (tDCS) studies of cognition and working memory in healthy populations.

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Medina, Jared; Cason, Samuel

2017-09-01

A substantial number of studies have been published over the last decade, claiming that transcranial direct current stimulation (tDCS) can influence performance on cognitive tasks. However, there is some skepticism regarding the efficacy of tDCS, and evidence from meta-analyses are mixed. One major weakness of these meta-analyses is that they only examine outcomes in published studies. Given biases towards publishing positive results in the scientific literature, there may be a substantial "file-drawer" of unpublished negative results in the tDCS literature. Furthermore, multiple researcher degrees of freedom can also inflate published p-values. Recently, Simonsohn, Nelson and Simmons (2014) created a novel meta-analytic tool that examines the distribution of significant p-values in a literature, and compares it to expected distributions with different effect sizes. Using this tool, one can assess whether the selected studies have evidential value. Therefore, we examined a random selection of studies that used tDCS to alter performance on cognitive tasks, and tDCS studies on working memory in a recently published meta-analysis (Mancuso et al., 2016). Using a p-curve analysis, we found no evidence that the tDCS studies had evidential value (33% power or greater), with the estimate of statistical power of these studies being approximately 14% for the cognitive studies, and 5% (what would be expected from randomly generated data) for the working memory studies. It is likely that previous tDCS studies are substantially underpowered, and we provide suggestions for future research to increase the evidential value of future tDCS studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells.

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Hyang-Mi Lee

2015-02-01

Full Text Available IFNγ signaling drives dendritic cells (DCs to promote type I T cell (Th1 immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.

tDCS and Robotics on Upper Limb Stroke Rehabilitation: Effect Modification by Stroke Duration and Type of Stroke.

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Straudi, Sofia; Fregni, Felipe; Martinuzzi, Carlotta; Pavarelli, Claudia; Salvioli, Stefano; Basaglia, Nino

2016-01-01

Objective. The aim of this exploratory pilot study is to test the effects of bilateral tDCS combined with upper extremity robot-assisted therapy (RAT) on stroke survivors. Methods. We enrolled 23 subjects who were allocated to 2 groups: RAT + real tDCS and RAT + sham-tDCS. Each patient underwent 10 sessions (5 sessions/week) over two weeks. Outcome measures were collected before and after treatment: (i) Fugl-Meyer Assessment-Upper Extremity (FMA-UE), (ii) Box and Block Test (BBT), and (iii) Motor Activity Log (MAL). Results. Both groups reported a significant improvement in FMA-UE score after treatment (p robotics on motor function. Patients with chronic and subcortical stroke benefited more from the treatments than patients with acute and cortical stroke, who presented very small changes. Conclusion. The additional use of bilateral tDCS to RAT seems to have a significant beneficial effect depending on the duration and type of stroke. These results should be verified by additional confirmatory studies.

Toward unraveling reading-related modulations of tDCS-induced neuroplasticity in the human visual cortex.

OpenAIRE

Antal, Andrea; Ambrus, Géza Gergely; Chaieb, Leila

2014-01-01

Stimulation using weak electrical direct currents has shown to be capable of inducing polarity-dependent diminutions or elevations in motor and visual cortical excitability. The aim of the present study was to test if reading during transcranial direct current stimulation (tDCS) is able to modify stimulation-induced plasticity in the visual cortex. Phosphene thresholds (PTs) in 12 healthy subjects were recorded before and after 10 min of anodal, cathodal, and sham tDCS in combination with rea...

A new mouse model of mild ornithine transcarbamylase deficiency (spf-j displays cerebral amino acid perturbations at baseline and upon systemic immune activation.

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Tatyana N Tarasenko

Full Text Available Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250 is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N. This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.

Treatment of visuospatial neglect with biparietal tDCS and cognitive training: a single-case study

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Anna-Katharine eBrem

2014-09-01

Full Text Available Symptoms of visuospatial neglect occur frequently after unilateral brain damage. Neglect hampers rehabilitation progress and is associated with reduced quality of life. However, existing treatment methods show limited efficacy. Transcranial direct current stimulation (tDCS is a neuromodulatory technique, which can be used to increase or decrease brain excitability. Its combination with conventional neglect therapy may enhance treatment efficacy.A 72-year-old male with a subacute ischaemic stroke of the right posterior cerebral artery suffering from visuospatial neglect, hemianopia, and hemiparesis was treated with biparietal tDCS and cognitive neglect therapy in a double-blind, sham-controlled single-case study. Four weeks of daily treatment sessions (5 days per week, 30 min were started 26 days post-stroke. During week 1 and 4 the patient received conventional neglect therapy, during week 2, conventional neglect therapy was combined once with sham and once with real biparietal tDCS. Week 3 consisted of daily sessions of real biparietal tDCS (1 mA, 20 min combined with neglect therapy. Outcome measures were assessed before, immediately after, as well as 1 week and 3 months after the end of treatment. They included subtests of the Test for Attentional Performance (TAP: covert attention (main outcome, alertness, visual field; the Neglect-Test (NET: line bisection, cancellation, copying; and activities of daily living (ADL. After real stimulation, covert attention allocation towards left-sided invalid stimuli was significantly improved, and line bisection and copying improved qualitatively as compared to sham stimulation. ADL were only improved at the 3-month follow-up. This single-case study demonstrates for the first time that combined application of tDCS and cognitive training may enhance training-induced improvements in measures of visuospatial neglect and is applicable in a clinical context.

Predicting tDCS treatment outcomes of patients with major depressive disorder using automated EEG classification.

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Al-Kaysi, Alaa M; Al-Ani, Ahmed; Loo, Colleen K; Powell, Tamara Y; Martin, Donel M; Breakspear, Michael; Boonstra, Tjeerd W

2017-01-15

Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). Standard tDCS treatment involves numerous sessions running over a few weeks. However, not all participants respond to this type of treatment. This study aims to investigate the feasibility of identifying MDD patients that respond to tDCS treatment based on resting-state electroencephalography (EEG) recorded prior to treatment commencing. We used machine learning to predict improvement in mood and cognition during tDCS treatment from baseline EEG power spectra. Ten participants with a current diagnosis of MDD were included. Power spectral density was assessed in five frequency bands: delta (0.5-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (13-30Hz) and gamma (30-100Hz). Improvements in mood and cognition were assessed using the Montgomery-Åsberg Depression Rating Scale and Symbol Digit Modalities Test, respectively. We trained the classifiers using three algorithms (support vector machine, extreme learning machine and linear discriminant analysis) and a leave-one-out cross-validation approach. Mood labels were accurately predicted in 8 out of 10 participants using EEG channels FC4-AF8 (accuracy=76%, p=0.034). Cognition labels were accurately predicted in 10 out of 10 participants using channels pair CPz-CP2 (accuracy=92%, p=0.004). Due to the limited number of participants (n=10), the presented results mainly aim to serve as a proof of concept. These finding demonstrate the feasibility of using machine learning to identify patients that will respond to tDCS treatment. These promising results warrant a larger study to determine the clinical utility of this approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability.

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Meron, Daniel; Hedger, Nicholas; Garner, Matthew; Baldwin, David S

2015-10-01

Transcranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE). We address the efficacy and safety of tDCS in MDE. The outcome measures were Hedges' g for continuous depression ratings, and categorical response and remission rates. A random effects model indicated that tDCS was superior to sham tDCS (k=11, N=393, g=0.30, 95% CI=[0.04, 0.57], p=0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k=9, LOR=0.36, 95% CI[-0.16, 0.88], p=0.176, remission: k=9, LOR=0.25, 95% CI [-0.42, 0.91], p=0.468). We estimated that for a study to detect the pooled continuous effect (g=0.30) at 80% power (alpha=0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively). tDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential influences of unilateral tDCS over the intraparietal cortex on numerical cognition

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Christina eArtemenko

2015-03-01

Full Text Available Recent neuro-imaging research identified the bilateral intraparietal sulcus (IPS to be a key area associated with number processing. However, causal structure-function relationships are hard to evaluate from neuro-imaging techniques such as fMRI. Nevertheless, brain stimulation methods like transcranial direct current stimulation (tDCS allow for investigating the functional relevance of the IPS for number processing. Following up on a study using bilateral bi-cephalic tDCS over the IPS, the current study aimed at evaluating the differential lateralized functional contributions of the left and right IPS to number processing using unilateral bi-cephalic tDCS over either the left or right IPS. Results indicated a right lateralization for the processing of the place-value structure of the Arabic number system. Importantly, the processing of number magnitude information was not affected by unilateral IPS corroborating the assumption that number magnitude is processed in the bilateral IPS. Taken together, these data suggest that even though number magnitude is represented bilaterally, the left and right IPS seem to contribute differentially to numerical cognition with respect to the processing of specific other aspects of numerical information.

Incidence of DCS and oxygen toxicity in chamber attendants: a 28-year experience.

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Witucki, Pete; Duchnick, Jay; Neuman, Tom; Grover, Ian

2013-01-01

Decompression sickness (DCS) and central nervous system oxygen toxicity are inherent risks for "inside" attendants (IAs) of hyperbaric chambers. At the Hyperbaric Medicine Center at the University of California San Diego (UCSD), protocols have been developed for decompressing IAs. Protocol 1: For a total bottom time (TBT) of less than 80 minutes at 2.4 atmospheres absolute (atm abs) or shallower, the U.S. Navy (1955) no-decompression tables were utilized. Protocol 2: For a TBT between 80 and 119 minutes IAs breathed oxygen for 15 minutes prior to initiation of ascent. Protocol 3: For a TBT between 120-139 minutes IAs breathed oxygen for 30 minutes prior to ascent. These protocols have been utilized for approximately 28 years and have produced zero cases of DCS and central nervous system oxygen toxicity. These results, based upon more than 24,000 exposures, have an upper limit of risk of DCS and oxygen toxicity of 0.02806 (95% CI) using UCSD IA decompression Protocol 1, 0.00021 for Protocol 2, and 0.00549 for Protocol 3. We conclude that the utilization of this methodology may be useful at other sea-level multiplace chambers.

Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

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Mário Henrique M Barros

Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

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Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

2013-01-01

Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

Semantic Feature Training in Combination with Transcranial Direct Current Stimulation (tDCS for Progressive Anomia

Directory of Open Access Journals (Sweden)

Jinyi Hung

2017-05-01

Full Text Available We examined the effectiveness of a 2-week regimen of a semantic feature training in combination with transcranial direct current stimulation (tDCS for progressive naming impairment associated with primary progressive aphasia (N = 4 or early onset Alzheimer’s Disease (N = 1. Patients received a 2-week regimen (10 sessions of anodal tDCS delivered over the left temporoparietal cortex while completing a language therapy that consisted of repeated naming and semantic feature generation. Therapy targets consisted of familiar people, household items, clothes, foods, places, hygiene implements, and activities. Untrained items from each semantic category provided item level controls. We analyzed naming accuracies at multiple timepoints (i.e., pre-, post-, 6-month follow-up via a mixed effects logistic regression and individual differences in treatment responsiveness using a series of non-parametric McNemar tests. Patients showed advantages for naming trained over untrained items. These gains were evident immediately post tDCS. Trained items also showed a shallower rate of decline over 6-months relative to untrained items that showed continued progressive decline. Patients tolerated stimulation well, and sustained improvements in naming accuracy suggest that the current intervention approach is viable. Future implementation of a sham control condition will be crucial toward ascertaining whether neurostimulation and behavioral treatment act synergistically or alternatively whether treatment gains are exclusively attributable to either tDCS or the behavioral intervention.

The Relationship Between Retinol/Retinol Binding Protein 4 ratio, resistin and inflammation in non diabetic obese Indonesian men

Directory of Open Access Journals (Sweden)

Anna Meiliana

2010-02-01

Full Text Available Aim To verify the correlation between Retinol/RBP4 Ratio, and resistin with inflammation (represented by hsCRP in non-diabetic obese Indonesian menMethods This was a cross sectional study using 125 subjects. Measured parameters were retinol, RBP4, resistin, and hsCRP. Correlation between retinol, RBP4, resistin, hsCRP and Retinol/RBP4 Ratio was calculated. Cut off point of hsCRP were classiied as follows: <1 mg/l for low risk of inflammation, 1-3 mg/l for moderate risk, and 3-10 mg/l for high risk (according to CVD risk. The Retinol/RBP4 ratio was dichotomized into high (>0.9 and low ratio (≤0.9. The cross tabulation test was performed to predict the inflammation trends described by Retinol/RBP4 Ratio and resistin.Results Retinol was found strongly correlated with RBP4 and resistin (r=0.53; p<0.01. A positive but not significant correlation was found between resistin and Retinol/RBP4 Ratio with hsCRP. In high ratio group, 17.6% subjects were found with low risk inflammation, 26.4% with moderate risk, and 20.8% with high risk, in low ratio group, 8% subjects were low risk inflammation, 20% moderate risk, and 7.2% high risk. Combination between ratio and resistin showed that in “high ratio and low resistin” group, 12% subjects have low risk of inflammation and 8% have high risk. Meanwhile in “low ratio and high resistin” group, 3.2% subjects were found having low risk and 13.6% high risk of inflammation.Conclusions Combination between Retinol/RBP4 Ratio and resistin showed better description about the inflammation risk in non-diabetic obese subjects compare to the ratio itself. (Med J Indones 2010; 19:57-63Keywords: Retinol, RBP4, resistin, hsCRP, obesity, inflammation

Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning.

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Nikolin, Stevan; Loo, Colleen K; Bai, Siwei; Dokos, Socrates; Martin, Donel M

2015-08-15

Declarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. To investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. HD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. HD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η(2)=0.29) and speed of responding during working memory performance (p=0.02, η(2)=0.35), but not accuracy (p=0.12, η(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η(2)=0.31) and reduced mid-list learning effects (p=0.01, η(2)=0.39), suggesting an inhibitory effect on learning. HD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing

Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.

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Weber, Matthew J; Messing, Samuel B; Rao, Hengyi; Detre, John A; Thompson-Schill, Sharon L

2014-08-01

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Copyright © 2014 Wiley Periodicals, Inc.

Decompression sickness among diving fishermen in Mexico: observational retrospective analysis of DCS in three sea cucumber fishing seasons.

Science.gov (United States)

Huchim-Lara, Oswaldo; Chin, Walter; Salas, Silvia; Rivera-Canul, Normando; Cordero-Romero, Salvador; Tec, Juan; Joo, Ellie; Mendez-Dominguez, Nina

2017-01-01

The probabilities of decompression sickness (DCS) among diving fishermen are higher than in any other group of divers. Diving behavior of artisanal fishermen has been directed mainly to target high-value species. The aim of this study was to learn about the occurrence of DCS derived from sea cucumber harvesting in the Yucatán Peninsula, Mexico. We conducted a retrospective chart review of diving fishermen treated at a multiplace hyperbaric chamber in Tizimín, Mexico. In total, 233 recompression therapies were rendered to 166 diving fishermen from 2014 to 2016. The average age was 36.7 ± 9.2 years (range: 20-59 years); 84.3% had experienced at least one DCS event previously. There was a correlation between age and DCS incidents (F: 8.3; R2: 0.07) and differences in the fishing depth between seasons (H: 9.99; p⟨0.05). Musculoskeletal pain was the most frequently reported symptom. Three divers, respectively, suffered permanent hearing loss, spinal cord injury and fatal outcome. Diving fishermen experience DCS at an alarmingly high rate, probably due to the type of species targeted, given the requirements in each case. Understanding divers' behaviors and their incentives while in pursuit of high-value species such as sea cucumber could help to find ways to mitigate health risks and help enforce regulation. Copyright© Undersea and Hyperbaric Medical Society.

A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS).

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Kasschau, Margaret; Sherman, Kathleen; Haider, Lamia; Frontario, Ariana; Shaw, Michael; Datta, Abhishek; Bikson, Marom; Charvet, Leigh

2015-12-26

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.

CORRELATION BETWEEN GUT MICROBIOTA AND DEVELOPMENT OF GLUCOSE INTOLERANCE IN B6.V-Lepob/J LEPTIN DEFICIENT MICE

DEFF Research Database (Denmark)

Ellekilde, Merete; Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris

, a large proportion of laboratory animals are used to study such diseases, but inter-individual variation in these animal models leads to the need for larger group sizes to reach statistical significance and adequate power. By standardizing the microbial and immunological status of laboratory animals we...... may therefore be able to produce animals with a more standardized response and less variation. This would lead to more precise results and a reduced number of animals needed for statistical significance. The aim of the present study was to investigate if the composition of the GM of B6.V...... the mechanisms of how the GM influences disease development is necessary, but based on these results it seems reasonable to assume, that by controlling the GM we may also influence disease development of type 2 diabetes in B6.V-Lepob/J leptin deficient mice, and thereby produce animals with less variation, which...

Impact of transcranial direct current stimulation (tDCS) on neuronal functions

NARCIS (Netherlands)

Das, S. (Suman); P.J. Holland (Peter); M.A. Frens (Maarten); O. Donchin (Opher)

2016-01-01

textabstractTranscranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates neuronal excitability by the application of a small electrical current. The low cost and ease of the technique has driven interest in potential clinical applications. However, outcomes

Impact of tDCS on Performance and Learning of Target Detection: Interaction with Stimulus Characteristics and Experimental Design

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Coffman, B. A.; Trumbo, M. C.; Flores, R. A.; Garcia, C. M.; van der Merwe, A. J.; Wassermann, E. M.; Weisend, M. P.; Clark, V. P.

2012-01-01

We have previously found that transcranial direct current stimulation (tDCS) over right inferior frontal cortex (RIFC) enhances performance during learning of a difficult visual target detection task (Clark et al., 2012). In order to examine the cognitive mechanisms of tDCS that lead to enhanced performance, here we analyzed its differential…

Effect of tDCS on task relevant and irrelevant perceptual learning of complex objects.

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Van Meel, Chayenne; Daniels, Nicky; de Beeck, Hans Op; Baeck, Annelies

2016-01-01

During perceptual learning the visual representations in the brain are altered, but these changes' causal role has not yet been fully characterized. We used transcranial direct current stimulation (tDCS) to investigate the role of higher visual regions in lateral occipital cortex (LO) in perceptual learning with complex objects. We also investigated whether object learning is dependent on the relevance of the objects for the learning task. Participants were trained in two tasks: object recognition using a backward masking paradigm and an orientation judgment task. During both tasks, an object with a red line on top of it were presented in each trial. The crucial difference between both tasks was the relevance of the object: the object was relevant for the object recognition task, but not for the orientation judgment task. During training, half of the participants received anodal tDCS stimulation targeted at the lateral occipital cortex (LO). Afterwards, participants were tested on how well they recognized the trained objects, the irrelevant objects presented during the orientation judgment task and a set of completely new objects. Participants stimulated with tDCS during training showed larger improvements of performance compared to participants in the sham condition. No learning effect was found for the objects presented during the orientation judgment task. To conclude, this study suggests a causal role of LO in relevant object learning, but given the rather low spatial resolution of tDCS, more research on the specificity of this effect is needed. Further, mere exposure is not sufficient to train object recognition in our paradigm.

Biotin deficiency up-regulates TNF-alpha production in murine macrophages.

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Kuroishi, Toshinobu; Endo, Yasuo; Muramoto, Koji; Sugawara, Shunji

2008-04-01

Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-alpha production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-alpha levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-alpha were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-alpha expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-alpha production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-kappaB family or AP-1. The TNF-alpha induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-alpha production or that biotin excess down-regulates TNF-alpha production, suggesting that biotin status may influence inflammatory diseases.

Isolation of Human Skin Dendritic Cell Subsets.

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Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

2016-01-01

Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

The role of primary auditory and visual cortices in temporal processing: A tDCS approach.

Science.gov (United States)

Mioni, G; Grondin, S; Forgione, M; Fracasso, V; Mapelli, D; Stablum, F

2016-10-15

Many studies showed that visual stimuli are frequently experienced as shorter than equivalent auditory stimuli. These findings suggest that timing is distributed across many brain areas and that "different clocks" might be involved in temporal processing. The aim of this study is to investigate, with the application of tDCS over V1 and A1, the specific role of primary sensory cortices (either visual or auditory) in temporal processing. Forty-eight University students were included in the study. Twenty-four participants were stimulated over A1 and 24 participants were stimulated over V1. Participants performed time bisection tasks, in the visual and the auditory modalities, involving standard durations lasting 300ms (short) and 900ms (long). When tDCS was delivered over A1, no effect of stimulation was observed on perceived duration but we observed higher temporal variability under anodic stimulation compared to sham and higher variability in the visual compared to the auditory modality. When tDCS was delivered over V1, an under-estimation of perceived duration and higher variability was observed in the visual compared to the auditory modality. Our results showed more variability of visual temporal processing under tDCS stimulation. These results suggest a modality independent role of A1 in temporal processing and a modality specific role of V1 in the processing of temporal intervals in the visual modality. Copyright © 2016 Elsevier B.V. All rights reserved.

Using cyber vulnerability testing techniques to expose undocumented security vulnerabilities in DCS and SCADA equipment

International Nuclear Information System (INIS)

Pollet, J.

2006-01-01

This session starts by providing an overview of typical DCS (Distributed Control Systems) and SCADA (Supervisory Control and Data Acquisition) architectures, and exposes cyber security vulnerabilities that vendors never admit, but are found through a comprehensive cyber testing process. A complete assessment process involves testing all of the layers and components of a SCADA or DCS environment, from the perimeter firewall all the way down to the end devices controlling the process, including what to look for when conducting a vulnerability assessment of real-time control systems. The following systems are discussed: 1. Perimeter (isolation from corporate IT or other non-critical networks) 2. Remote Access (third Party access into SCADA or DCS networks) 3. Network Architecture (switch, router, firewalls, access controls, network design) 4. Network Traffic Analysis (what is running on the network) 5. Host Operating Systems Hardening 6. Applications (how they communicate with other applications and end devices) 7. End Device Testing (PLCs, RTUs, DCS Controllers, Smart Transmitters) a. System Discovery b. Functional Discovery c. Attack Methodology i. DoS Tests (at what point does the device fail) ii. Malformed Packet Tests (packets that can cause equipment failure) iii. Session Hijacking (do anything that the operator can do) iv. Packet Injection (code and inject your own SCADA commands) v. Protocol Exploitation (Protocol Reverse Engineering / Fuzzing) This paper will provide information compiled from over five years of conducting cyber security testing on control systems hardware, software, and systems. (authors)

Using cyber vulnerability testing techniques to expose undocumented security vulnerabilities in DCS and SCADA equipment

Energy Technology Data Exchange (ETDEWEB)

Pollet, J. [PlantData Technologies, Inc., 1201 Louisiana Street, Houston, TX 77002 (United States)

2006-07-01

This session starts by providing an overview of typical DCS (Distributed Control Systems) and SCADA (Supervisory Control and Data Acquisition) architectures, and exposes cyber security vulnerabilities that vendors never admit, but are found through a comprehensive cyber testing process. A complete assessment process involves testing all of the layers and components of a SCADA or DCS environment, from the perimeter firewall all the way down to the end devices controlling the process, including what to look for when conducting a vulnerability assessment of real-time control systems. The following systems are discussed: 1. Perimeter (isolation from corporate IT or other non-critical networks) 2. Remote Access (third Party access into SCADA or DCS networks) 3. Network Architecture (switch, router, firewalls, access controls, network design) 4. Network Traffic Analysis (what is running on the network) 5. Host Operating Systems Hardening 6. Applications (how they communicate with other applications and end devices) 7. End Device Testing (PLCs, RTUs, DCS Controllers, Smart Transmitters) a. System Discovery b. Functional Discovery c. Attack Methodology i. DoS Tests (at what point does the device fail) ii. Malformed Packet Tests (packets that can cause equipment failure) iii. Session Hijacking (do anything that the operator can do) iv. Packet Injection (code and inject your own SCADA commands) v. Protocol Exploitation (Protocol Reverse Engineering / Fuzzing) This paper will provide information compiled from over five years of conducting cyber security testing on control systems hardware, software, and systems. (authors)

Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

Science.gov (United States)

McInnes, Kerry J.; Smith, Lee B.; Hunger, Nicole I.; Saunders, Philippa T.K.; Andrew, Ruth; Walker, Brian R.

2012-01-01

Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency. PMID:22415878

The critical role of cognitive-based trait differences in transcranial direct current stimulation (tDCS) suppression of food craving and eating in frank obesity.

Science.gov (United States)

Ray, Mary Katherine; Sylvester, Maria D; Osborn, Lauren; Helms, Joel; Turan, Bulent; Burgess, Emilee E; Boggiano, Mary M

2017-09-01

Obesity remains a major public health concern and novel treatments are needed. Transcranial direct current stimulation (tDCS) is a neuromodulation technique shown to reduce food craving and consumption, especially when targeting the dorsolateral prefrontal cortex (DLPFC) with a right anode/left cathode electrode montage. Despite the implications to treat frank (non-bingeeating) obesity, no study has tested the right anode/left cathode montage in this population. Additionally, most tDCS appetite studies have not controlled for differences in traits under DLPFC control that may influence how well one responds to tDCS. Hence, N = 18 (10F/8M) adults with frank obesity completed the Dutch Eating Behavior Questionnaire-Restraint and Barratt Impulsiveness Scale, and received 20 min of 2 mA active tDCS and control tDCS session. Craving and eating was assessed at both sessions with a food photo "wanting" test and in-lab measures of total, preferred, and less-preferred kilocalories consumed of three highly palatable snack foods. While main effects of tDCS vs. control were not found, significant differences emerged when trait scores were controlled. tDCS reduced food craving in females with lower attention-type impulsiveness (p = 0.047), reduced preferred-food consumption in males with lower intent to restrict calories (p = 0.024), and reduced total food consumption in males with higher non-planning-type impulsiveness (p = 0.009) compared to control tDCS. This is the first study to find significant reductions in food craving and consumption in a sample with frank obesity using the most popular tDCS montage in appetite studies. The results also highlight the cognitive-based heterogeneity of individuals with obesity and the importance of considering these differences when evaluating the efficacy of DLPFC-targeted tDCS in future studies aimed at treating obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cerebellar tDCS does not improve performance in probabilistic classification learning

NARCIS (Netherlands)

N. Seyed Majidi; M.C. Verhage (Claire); O. Donchin (Opher); P.J. Holland (Peter); M.A. Frens (Maarten); J.N. van der Geest (Jos)

2016-01-01

textabstractIn this study, the role of the cerebellum in a cognitive learning task using transcranial direct current stimulation (tDCS) was investigated. Using a weather prediction task, subjects had to learn the probabilistic associations between a stimulus (a combination of cards) and an outcome

The Effect of Transcranial Direct Current Stimulation (tDCS) Electrode Size and Current Intensity on Motor Cortical Excitability: Evidence From Single and Repeated Sessions.

Science.gov (United States)

Ho, Kerrie-Anne; Taylor, Janet L; Chew, Taariq; Gálvez, Verònica; Alonzo, Angelo; Bai, Siwei; Dokos, Socrates; Loo, Colleen K

2016-01-01

Current density is considered an important factor in determining the outcomes of tDCS, and is determined by the current intensity and electrode size. Previous studies examining the effect of these parameters on motor cortical excitability with small sample sizes reported mixed results. This study examined the effect of current intensity (1 mA, 2 mA) and electrode size (16 cm(2), 35 cm(2)) on motor cortical excitability over single and repeated tDCS sessions. Data from seven studies in 89 healthy participants were pooled for analysis. Single-session data were analyzed using mixed effects models and repeated-session data were analyzed using mixed design analyses of variance. Computational modeling was used to examine the electric field generated. The magnitude of increases in excitability after anodal tDCS was modest. For single-session tDCS, the 35 cm(2) electrodes produced greater increases in cortical excitability compared to the 16 cm(2) electrodes. There were no differences in the magnitude of cortical excitation produced by 1 mA and 2 mA tDCS. The repeated-sessions data also showed that there were greater increases in excitability with the 35 cm(2) electrodes. Further, repeated sessions of tDCS with the 35 cm(2) electrodes resulted in a cumulative increase in cortical excitability. Computational modeling predicted higher electric field at the motor hotspot for the 35 cm(2) electrodes. 2 mA tDCS does not necessarily produce larger effects than 1 mA tDCS in healthy participants. Careful consideration should be given to the exact positioning, size and orientation of tDCS electrodes relative to cortical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Review Finds No Evidence of Cognitive Effects in Healthy Populations From Single-session Transcranial Direct Current Stimulation (tDCS).

Science.gov (United States)

Horvath, Jared Cooney; Forte, Jason D; Carter, Olivia

2015-01-01

Over the last 15-years, transcranial direct current stimulation (tDCS), a relatively novel form of neuromodulation, has seen a surge of popularity in both clinical and academic settings. Despite numerous claims suggesting that a single session of tDCS can modulate cognition in healthy adult populations (especially working memory and language production), the paradigms utilized and results reported in the literature are extremely variable. To address this, we conduct the largest quantitative review of the cognitive data to date. Single-session tDCS data in healthy adults (18-50) from every cognitive outcome measure reported by at least two different research groups in the literature was collected. Outcome measures were divided into 4 broad categories: executive function, language, memory, and miscellaneous. To account for the paradigmatic variability in the literature, we undertook a three-tier analysis system; each with less-stringent inclusion criteria than the prior. Standard mean difference values with 95% CIs were generated for included studies and pooled for each analysis. Of the 59 analyses conducted, tDCS was found to not have a significant effect on any - regardless of inclusion laxity. This includes no effect on any working memory outcome or language production task. Our quantitative review does not support the idea that tDCS generates a reliable effect on cognition in healthy adults. Reasons for and limitations of this finding are discussed. This work raises important questions regarding the efficacy of tDCS, state-dependency effects, and future directions for this tool in cognitive research. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of prefrontal cortex transcranial direct current stimulation (tDCS) on food craving and temporal discounting in women with frequent food cravings.

Science.gov (United States)

Kekic, Maria; McClelland, Jessica; Campbell, Iain; Nestler, Steffen; Rubia, Katya; David, Anthony S; Schmidt, Ulrike

2014-07-01

Bulimia nervosa, binge-eating disorder, and some forms of obesity are characterised by compulsive overeating that is often precipitated by food craving. Transcranial direct current stimulation (tDCS) has been used to suppress food cravings, but there is insufficient evidence to support its application in clinical practice. Furthermore, the potential moderating role of impulsivity has not been considered. This study used a randomised within-subjects crossover design to examine whether a 20-minute session of sham-controlled bilateral tDCS to the dorsolateral prefrontal cortex (anode right/cathode left) would transiently modify food cravings and temporal discounting (TD; a measure of choice impulsivity) in 17 healthy women with frequent food cravings. Whether the effects of tDCS on food craving were moderated by individual differences in TD behaviour was also explored. Participants were exposed to food and a film of people eating, and food cravings and TD were assessed before and after active and sham stimulation. Craving for sweet but not savoury foods was reduced following real tDCS. Participants that exhibited more reflective choice behaviour were more susceptible to the anti-craving effects of tDCS than those that displayed more impulsive choice behaviour. No differences were seen in TD or food consumption after real versus sham tDCS. These findings support the efficacy of tDCS in temporarily lowering food cravings and identify the moderating role of TD behaviour. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preliminary Evidence of "Other-Race Effect"-Like Behavior Induced by Cathodal-tDCS over the Right Occipital Cortex, in the Absence of Overall Effects on Face/Object Processing.

Science.gov (United States)

Costantino, Andrea I; Titoni, Matilde; Bossi, Francesco; Premoli, Isabella; Nitsche, Michael A; Rivolta, Davide

2017-01-01

Neuromodulation techniques such as tDCS have provided important insight into the neurophysiological mechanisms that mediate cognition. Albeit anodal tDCS (a-tDCS) often enhances cognitive skills, the role of cathodal tDCS (c-tDCS) in visual cognition is largely unexplored and inconclusive. Here, in a single-blind, sham-controlled study, we investigated the offline effects of 1.5 mA c-tDCS over the right occipital cortex of 86 participants on four tasks assessing perception and memory of both faces and objects. Results demonstrated that c-tDCS does not overall affect performance on the four tasks. However, post-hoc exploratory analysis on participants' race (Caucasian vs. non-Caucasians), showed a "face-specific" performance decrease (≈10%) in non-Caucasian participants only . This preliminary evidence suggests that c-tDCS can induce "other-race effect (ORE)-like" behavior in non-Caucasian participants that did not show any ORE before stimulation (and in case of sham stimulation). Our results add relevant information about the breadth of cognitive processes and visual stimuli that can be modulated by c-tDCS, about the design of effective neuromodulation protocols, and have important implications for the potential neurophysiological bases of ORE.

Deft Control Software (DCS) for Remote Robotic Operations with Underlying Structure, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — BluHaptics proposes Deft Control Software (DCS), which utilizes machine learning to enable intuitive and efficient control of robotic arms in remote operations with...

A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters.

Science.gov (United States)

Dedoncker, Josefien; Brunoni, Andre R; Baeken, Chris; Vanderhasselt, Marie-Anne

2016-01-01

Research into the effects of transcranial direct current stimulation of the dorsolateral prefrontal cortex on cognitive functioning is increasing rapidly. However, methodological heterogeneity in prefrontal tDCS research is also increasing, particularly in technical stimulation parameters that might influence tDCS effects. To systematically examine the influence of technical stimulation parameters on DLPFC-tDCS effects. We performed a systematic review and meta-analysis of tDCS studies targeting the DLPFC published from the first data available to February 2016. Only single-session, sham-controlled, within-subject studies reporting the effects of tDCS on cognition in healthy controls and neuropsychiatric patients were included. Evaluation of 61 studies showed that after single-session a-tDCS, but not c-tDCS, participants responded faster and more accurately on cognitive tasks. Sub-analyses specified that following a-tDCS, healthy subjects responded faster, while neuropsychiatric patients responded more accurately. Importantly, different stimulation parameters affected a-tDCS effects, but not c-tDCS effects, on accuracy in healthy samples vs. increased current density and density charge resulted in improved accuracy in healthy samples, most prominently in females; for neuropsychiatric patients, task performance during a-tDCS resulted in stronger increases in accuracy rates compared to task performance following a-tDCS. Healthy participants respond faster, but not more accurate on cognitive tasks after a-tDCS. However, increasing the current density and/or charge might be able to enhance response accuracy, particularly in females. In contrast, online task performance leads to greater increases in response accuracy than offline task performance in neuropsychiatric patients. Possible implications and practical recommendations are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential sensory cortical involvement in auditory and visual sensorimotor temporal recalibration: Evidence from transcranial direct current stimulation (tDCS).

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Aytemür, Ali; Almeida, Nathalia; Lee, Kwang-Hyuk

2017-02-01

Adaptation to delayed sensory feedback following an action produces a subjective time compression between the action and the feedback (temporal recalibration effect, TRE). TRE is important for sensory delay compensation to maintain a relationship between causally related events. It is unclear whether TRE is a sensory modality-specific phenomenon. In 3 experiments employing a sensorimotor synchronization task, we investigated this question using cathodal transcranial direct-current stimulation (tDCS). We found that cathodal tDCS over the visual cortex, and to a lesser extent over the auditory cortex, produced decreased visual TRE. However, both auditory and visual cortex tDCS did not produce any measurable effects on auditory TRE. Our study revealed different nature of TRE in auditory and visual domains. Visual-motor TRE, which is more variable than auditory TRE, is a sensory modality-specific phenomenon, modulated by the auditory cortex. The robustness of auditory-motor TRE, unaffected by tDCS, suggests the dominance of the auditory system in temporal processing, by providing a frame of reference in the realignment of sensorimotor timing signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

No significant effect of transcranial direct current stimulation (tDCS) found on simple motor reaction time comparing 15 different simulation protocols.

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Horvath, Jared Cooney; Carter, Olivia; Forte, Jason D

2016-10-01

Research exploring the behavioral impact of transcranial direct current stimulation (tDCS) over M1 has produced homogenous results. The most common explanations to address this homogeneity concerns the differential impact of varied tDCS parameters (such as stimulation intensity or electrode montage). To explore this, we systematically examined the effects of 15 different tDCS protocols on a well-elucidated neurobehavioral system: simple visual motor reaction time (smRT). For the initial phase of this study, 150 healthy participants were randomly assigned to one of 5 experimental groups (2mA anodal, 2mA cathodal, 1mA anodal, 1mA cathodal, or sham) across 3 different conditions (orbitofrontal, bilateral, or extracephalic reference electrode location). The active electrode was always placed over M1 and tDCS lasted for 20min. Starting ~5min prior to stimulation and running continuously for ~30min, participants were repeatedly presented with a visual cue centered on a computer monitor and asked to press a response button as quickly as possible at stimulus onset (stimuli number: 100 pre-, 400 during-, and 100-post stimulation - interstimulus interval: 1-3s). Ex-gaussian distribution curves, miss, and error rates were determined for each normalized batch of 100 RTs and compared using a two-way ANOVA. As the largest group differences were seen with 2mA anodal (compared to sham) stimulation using an orbitofrontal montage, an additional 60 healthy participants were recruited to further test for significance in this condition. No significant impact of tDCS was seen on any parameter of smRT distribution, error rate, or miss rate, regardless of polarity, stimulation intensity, electrode montage, or stimulation-to-task relationship. Our results suggest that tDCS over M1 might not have a predictable or reliable effect on short duration smRT. Our results raise interesting questions regarding the mechanisms by which tDCS might modulate more complex motor behaviors. Additional

Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia.

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Fröhlich, F; Burrello, T N; Mellin, J M; Cordle, A L; Lustenberger, C M; Gilmore, J H; Jarskog, L F

2016-03-01

Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizophrenia after five days of twice-daily transcranial direct current stimulation (tDCS) that simultaneously targeted left dorsolateral prefrontal cortex and left temporo-parietal cortex. We hypothesized that once-daily tDCS with stimulation electrodes over left frontal and temporo-parietal areas reduces auditory hallucinations in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled study that evaluated five days of daily tDCS of the same cortical targets in 26 outpatients with schizophrenia and schizoaffective disorder with auditory hallucinations. We found a significant reduction in auditory hallucinations measured by the Auditory Hallucination Rating Scale (F2,50=12.22, PtDCS for treatment of auditory hallucinations and the pronounced response in the sham-treated group in this study contrasts with the previous finding and demonstrates the need for further optimization and evaluation of noninvasive brain stimulation strategies. In particular, higher cumulative doses and higher treatment frequencies of tDCS together with strategies to reduce placebo responses should be investigated. Additionally, consideration of more targeted stimulation to engage specific deficits in temporal organization of brain activity in patients with auditory hallucinations may be warranted. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effects of transcranial direct current stimulation (tDCS) on cognition, symptoms, and smoking in schizophrenia: A randomized controlled study.

Science.gov (United States)

Smith, Robert C; Boules, Sylvia; Mattiuz, Sanela; Youssef, Mary; Tobe, Russell H; Sershen, Henry; Lajtha, Abel; Nolan, Karen; Amiaz, Revital; Davis, John M

2015-10-01

Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved. Transcranial direct current stimulation (tDCS) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a randomized controlled study for these effects in schizophrenia. We conducted a randomized double-blind, sham-controlled study of the effects of 5 sessions of tDCS (2 milliamps for 20minutes) on cognition, psychiatric symptoms, and smoking and cigarette craving in 37 outpatients with schizophrenia or schizoaffective disorder who were current smokers. Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery (MCCB), with the primary outcome measure, the MCCB Composite score. Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS session in MCCB Composite score (p=0.008) and on the MCCB Working Memory (p=0.002) and Attention-Vigilance (p=0.027) domain scores, with large effect sizes. MCCB Composite and Working Memory domain scores remained significant at Benjamini-Hochberg corrected significance levels (α=0.05). There were no statistically significant effects on secondary outcome measures of psychiatric symptoms (PANSS scores), hallucinations, cigarette craving, or cigarettes smoked. The positive effects of tDCS on cognitive performance suggest a potential efficacious treatment for cognitive deficits in partially recovered chronic schizophrenia outpatients that should be further investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

The Effects of Transcranial Direct Current Stimulation (tDCS on Psychomotor and Visual Perception Functions Related to Driving Skills

Directory of Open Access Journals (Sweden)

Alexander Brunnauer

2018-01-01

Full Text Available Objective: It could be demonstrated that anodal transcranial direct current stimulation (tDCS of the left dorsolateral prefrontal cortex (DLPFC enhances accuracy in working memory tasks and reaction time in healthy adults and thus may also have an influence on complex everyday tasks like driving a car. However, no studies have applied tDCS to psychomotor skills related to a standard driving test so far.Methods: 10 female and 5 male healthy adults without any medication and history of psychiatric or neurological illness were randomly assigned to two groups receiving active and sham stimulation in a double blind, cross-over study design. Standardized computerized psychomotor tests according to the German guidelines for road and traffic safety were administered at baseline. Then they performed the same tests during an anodal or sham tDCS of the left DLPFC in two separated sessions.Results: No significant improvements in skills related to driving performance like visual perception, stress tolerance, concentration, and vigilance could be shown after left anodal prefrontal tDCS. Side effects were low and did not differ between active and sham stimulation.Conclusions: The findings of our study indicate that left prefrontal tDCS may not alter driving skills affording more automated action patterns but as shown in previous studies may have an influence on driving behavior requiring executive control processes. This however has to be proved in future studies and within greater samples.

Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease.

Science.gov (United States)

Chen, Yumay; Chiang, Huai-Chin; Litchfield, Patricia; Pena, Michelle; Juang, Charity; Riley, Daniel J

2014-07-17

Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron.

Non-linear effects of transcranial direct current stimulation as a function of individual baseline performance: Evidence from biparietal tDCS influence on lateralized attention bias.

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Benwell, Christopher S Y; Learmonth, Gemma; Miniussi, Carlo; Harvey, Monika; Thut, Gregor

2015-08-01

Transcranial direct current stimulation (tDCS) is a well-established technique for non-invasive brain stimulation (NIBS). However, the technique suffers from a high variability in outcome, some of which is likely explained by the state of the brain at tDCS-delivery but for which explanatory, mechanistic models are lacking. Here, we tested the effects of bi-parietal tDCS on perceptual line bisection as a function of tDCS current strength (1 mA vs 2 mA) and individual baseline discrimination sensitivity (a measure associated with intrinsic uncertainty/signal-to-noise balance). Our main findings were threefold. We replicated a previous finding (Giglia et al., 2011) of a rightward shift in subjective midpoint after Left anode/Right cathode tDCS over parietal cortex (sham-controlled). We found this effect to be weak over our entire sample (n = 38), but to be substantial in a subset of participants when they were split according to tDCS-intensity and baseline performance. This was due to a complex, nonlinear interaction between these two factors. Our data lend further support to the notion of state-dependency in NIBS which suggests outcome to depend on the endogenous balance between task-informative 'signal' and task-uninformative 'noise' at baseline. The results highlight the strong influence of individual differences and variations in experimental parameters on tDCS outcome, and the importance of fostering knowledge on the factors influencing tDCS outcome across cognitive domains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Food craving, food choice and consumption: The role of impulsivity and sham-controlled tDCS stimulation of the right dlPFC.

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Georgii, Claudio; Goldhofer, Philipp; Meule, Adrian; Richard, Anna; Blechert, Jens

2017-08-01

Impulsivity has been found to be associated with overeating and obesity. Transcranial direct current stimulation (tDCS) may enhance inhibitory control while reducing food craving and intake. Thus, the aim of the present study was to investigate whether tDCS stimulation modifies food choice, craving and consumption as a function of trait impulsivity. Forty-two predominantly healthy-weight women received active tDCS stimulation to the right dorsolateral prefrontal cortex and sham stimulation in a within participant design. Trait impulsivity was measured with a short form of the Barratt Impulsiveness Scale. Participants completed a computerized food-choice task, during which their mouse movements were traced. Current food craving was measured by a modified version of the Food Cravings Questionnaire-State as well as by desire to eat ratings for food pictures. Food intake was measured in a taste test. There were no tDCS effects on any of the dependent variables. Trait impulsivity (and non-planning impulsivity in particular) was positively associated with higher calorie intake in the taste test, irrespective of tDCS stimulation. The current findings question the efficacy of single-session tDCS stimulation of the right dLPFC to reduce food craving, high caloric food choice and calorie intake in non-selected, predominantly healthy weight women. However, they do support the idea that trait impulsivity is related to overeating and, therefore, may be a risk factor for obesity. Future research needs to specify which appetitive behaviors can be modulated by brain stimulation and which populations might profit from it the most. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

Directory of Open Access Journals (Sweden)

Henrique Borges da Silva

2015-02-01

Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

Science.gov (United States)

Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra Dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D'Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

2015-02-01

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins.

LENUS (Irish Health Repository)

Ryan, Anthony

2011-06-01

Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H\\/HeN and C3H\\/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H\\/HeJ mice and failed to induce a subsequent Th cell response. TLR4(-\\/-) and Myd88(-\\/-), but not TRIF(-\\/-) mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system.

Transcranial direct current stimulation (tDCS) and its influence on analgesics effectiveness in patients suffering from migraine headache.

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Przeklasa-Muszyńska, Anna; Kocot-Kępska, Magdalena; Dobrogowski, Jan; Wiatr, Maciej; Mika, Joanna

2017-08-01

Headache is one of the most common conditions troubling nearly 45% of the world's population. Migraine headache itself, being more common among women, affects 7-18% of people. As much as 20-30% of the population report accompanying aura and neurological symptoms. In many cases, migraine headache can be effectively treated with suitably selected pharmacotherapies which include drugs used in symptomatic treatment. Frequent occurrence of the condition is treated with prophylaxis, which often fails. Neuromodulating methods are part of the multidirectional treatment and they may be valuable complement to pharmacotherapy. Our study evaluates the impact of the transcranial direct current stimulation (tDCS) on the consumption of drugs and on pain conditions (frequency, duration, intensity). We recruited 50 patients with migraine headache (30 with aura, 20 without aura) refractory to pharmacological therapy. In 30 patients (18 with aura, 12 without aura) previous unsatisfactory treatment was supplemented with tDCS performed tenfold. 20 patients (12 with aura, 8 without aura) from a control group were treated with pharmacological methods The observation continued for 30 days after the stimulation. After tDCS, a reduction in the consumption of analgesics and triptans was reported. Additionally, we monitored pain intensity decrease during pain episodes, duration of episodes and the number of pain days. The subjective assessment of pain reduction in migraine patients encompassed 36-40% after tDCS much more effective in comparison to group with only pharmacotherapy (10-12.5%). The study suggests that tDCS may be safe and useful clinical tool in migraine prophylaxis and treatment. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Site-dependent effects of tDCS uncover dissociations in the communication network underlying the processing of visual search.

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Ball, Keira; Lane, Alison R; Smith, Daniel T; Ellison, Amanda

2013-11-01

The right posterior parietal cortex (rPPC) and the right frontal eye field (rFEF) form part of a network of brain areas involved in orienting spatial attention. Previous studies using transcranial magnetic stimulation (TMS) have demonstrated that both areas are critically involved in the processing of conjunction visual search tasks, since stimulation of these sites disrupts performance. This study investigated the effects of long term neuronal modulation to rPPC and rFEF using transcranial direct current stimulation (tDCS) with the aim of uncovering sharing of these resources in the processing of conjunction visual search tasks. Participants completed four blocks of conjunction search trials over the course of 45 min. Following the first block they received 15 min of either cathodal or anodal stimulation to rPPC or rFEF, or sham stimulation. A significant interaction between block and stimulation condition was found, indicating that tDCS caused different effects according to the site (rPPC or rFEF) and type of stimulation (cathodal, anodal, or sham). Practice resulted in a significant reduction in reaction time across the four blocks in all conditions except when cathodal tDCS was applied to rPPC. The effects of cathodal tDCS over rPPC are subtler than those seen with TMS, and no effect of tDCS was evident at rFEF. This suggests that rFEF has a more transient role than rPPC in the processing of conjunction visual search and is robust to longer-term methods of neuro-disruption. Our results may be explained within the framework of functional connectivity between these, and other, areas. Copyright © 2013 Elsevier Inc. All rights reserved.

Characterization and properties of biosurfactants produced by a newly isolated strain Bacillus methylotrophicus DCS1 and their applications in enhancing solubility of hydrocarbon.

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Jemil, Nawel; Ben Ayed, Hanen; Hmidet, Noomen; Nasri, Moncef

2016-11-01

Six biosurfactant-producing bacteria were isolated from hydrocarbon contaminated soils in Sfax, Tunisia. Isolates were screened for biosurfactant production by different conventional methods including hemolytic activity, surface tension reduction, drop-collapsing and oil displacement tests. All these screening tests show that all the isolates behave differently. Among the isolated bacteria, DCS1 strain was selected for further studies based on its highest activities and it was identified as Bacillus methylotrophicus DCS1. This strain was found to be a potent producer of biosurfactant when cultivated in mineral-salts medium supplemented with diesel oil (2 %, v/v) as a sole carbon source. Physicochemical properties and stability of biosurfactants synthesized by B. methylotrophicus DCS1 were investigated. The produced biosurfactants DCS1, from Landy medium, possess high surface activity that could lower the surface tension of water to a value of 31 from 72 mN m(-1) and have a critical micelle concentration (CMC) of 100 mg L(-1). Compared with SDS and Tween 80, biosurfactants showed excellent emulsification activities against different hydrocarbon substrates and high solubilization efficiency towards diesel oil. Biosurfactants DCS1 showed good stability in a wide range of temperature, pH and salinity. These results suggested that biosurfactants produced by B. methylotrophicus DCS1 could be an alternative to chemically synthesized surfactants for use in bioremediation processes to enhance the solubility of hydrophobic compounds.

Anodal tDCS of dorsolateral prefontal cortex during an Implicit Association Test

NARCIS (Netherlands)

Gladwin, T.E.; den Uyl, T.E.; Wiers, R.W.

2012-01-01

Anodal stimulation of dorsolateral prefrontal cortex by transcranial Direct Current Stimulation (tDCS) has been shown to enhance performance on working memory tasks. However, it is not yet known precisely which aspects of working memory - a broad theoretical concept including short-term memory and

Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC).

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Boggio, Paulo S; Zaghi, Soroush; Villani, Ana Beatriz; Fecteau, Shirley; Pascual-Leone, Alvaro; Fregni, Felipe

2010-12-01

Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n=8), right anodal/left cathodal tDCS of DLPFC (n=9), or sham stimulation (n=8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Research and practice on NPP safety DCS application software V and V defect classification system

International Nuclear Information System (INIS)

Zhang Dongwei; Li Yunjian; Li Xiangjian

2012-01-01

One of the most significant aims of Verification and Validation (V and V) is to find software errors and risks, especially for a DCS application software designed for nuclear power plant (NPP). Through classifying and analyzing errors, a number of obtained data can be utilized to estimate current status and potential risks of software development and improve the quality of project. A method of error classification is proposed, which is applied to whole V and V life cycle, using a MW pressurized reactor project as an example. The purpose is to analyze errors discovered by V and V activities, and result in improvement of safety critical DCS application software. (authors)

Culture supernatants of oral cancer cells induce impaired IFN-α production of pDCs partly through the down-regulation of TLR-9 expression.

Science.gov (United States)

Han, Nannan; Zhang, Zun; Jv, Houyu; Hu, Jingzhou; Ruan, Min; Zhang, Chenping

2018-06-05

The aim of the present study was to investigate whether tumor-derived supernatants down-regulate the immune function of plasmacytoid dendritic cells (pDCs) in oral cancer and the potential molecular mechanisms of this effect. Immunohistochemistry (IHC) and flow cytometry were used to detect tumor-infiltrating and peripheral blood pDCs. MTS and flow cytometry were employed to evaluate the immune response of CD4 + T cells. Real-time PCR and ELISA assays were used to identify TLR-7 and TLR-9 expression, IFN-α production and tumor-secreted soluble cytokines. The proportion of pDCs (0.121%±0.043%) was significantly higher in Oral squamous cell carcinoma (OSCC) samples than in normal tissue (0.023%±0.016%) (P = 0.021). TLR9 mRNA was significantly lower in tumor-infiltrating pDCs and positively correlated to low IFN-α production (r = 0.956; Poral cancer cells negatively regulated TLR9 mRNA expression and the subsequent IFN-α production of pDCs, which inhibited the immune response of CD4 + T cells. The neutralizing antibodies blocking assay showed that the specific inhibitory effect of pDC functionality was associated with the soluble fraction of the oral cancer environment, which is mainly mediated by IL-10 and TGF-β cooperation. Tumor-derived supernatants may impair the function of tumor-infiltrating pDCs, which subsequently decreases the immune response of CD4 + T cells in human oral cancer through TGF-β- and IL-10- dependent mechanisms. Careful manipulation of these impaired pDCs may help develop an important alternative immunotherapy for the treatment of oral cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Repulsive guidance molecule a blockade exerts the immunoregulatory function in DCs stimulated with ABP and LPS.

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Xu, Xuxu; Gao, Yan; Zhai, Zhiyong; Zhang, Shuo; Shan, Fengping; Feng, Juan

2016-08-02

Repulsive guidance molecule a (RGMa) is an axonal guidance molecule that has recently found to exert function in immune system. This study evaluated the function of RGMa in modulation of dendritic cells (DCs) function stimulated with Achyranthes bidentata polysaccharide (ABP) and lipopolysaccharide (LPS) using a RGMa-neutralizing antibody. Compared with the Control-IgG/ABP and Control-IgG/LPS groups, DCs in the Anti-RGMa/ABP and Anti-RGMa/LPS groups 1) showed small, round cells with a few cell processes and organelles, and many pinocytotic vesicles; 2) had decreased MHC II, CD86, CD80, and CD40 expression; 3) displayed the decreased IL-12p70, IL-1β and TNF-α levels and increased IL-10 secretion; 4) had a high percentage of FITC-dextran uptake; and 5) displayed a reduced ability to drive T cell proliferation and reinforced T cell polarization toward a Th2 cytokine pattern. We conclude that DCs treated with RGMa-neutralizing antibodies present with tolerogenic and immunoregulatory characteristics, which provides new insights into further understanding of the function of RGMa.

The effects of anodal-tDCS on corticospinal excitability enhancement and its after-effects: conventional versus unihemispheric concurrent dual-site stimulation

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Bita eVaseghi

2015-09-01

Full Text Available Previous researchers have approved the ability of anodal transcranial direct current stimulation (a-tDCS of the primary motor cortex (M1 to enhance corticospinal excitability (CSE. The primary aim of the current study was to investigate the effect of concurrent stimulation of M1 and a functionally connected cortical site of M1 on CSE modulation. This new technique is called unihemispheric concurrent dual-site a-tDCS (a-tDCSUHCDS. The secondary aim was to investigate the mechanisms underlying the efficacy of this new approach in healthy individuals. In a randomized crossover study, 12 healthy right-handed volunteers received a-tDCS under five conditions: a-tDCS of M1, a-tDCSUHCDS of M1– dorsolateral prefrontal cortex (DLPFC, a-tDCSUHCDS of M1– primary sensory cortex (S1, a-tDCSUHCDS of M1– primary visual cortex (V1, and sham a-tDCSUHCDS. Peak-to-peak amplitude of transcranial magnetic stimulation (TMS induced MEPs, short-interval intracortical inhibition and intracortical facilitation were assessed before and four times after each condition. A-tDCSUHCDS conditions induced larger MEPs than conventional a-tDCS. The level of M1 CSE was significantly higher following a-tDCSUHCDS of M1-DLPFC than other a-tDCSUHCDS conditions (P < 0.001, and lasted for over 24 hours. The paired-pulse TMS results after a-tDCS of M1-DLPFC showed significant facilitatory increase and inhibitory change. A-tDCSUHCDS of M1-DLPFC increases M1 CSE twofold that of conventional a-tDCS. A-tDCSUHCDS of M1-DLPFC enhances the activity of glutamergic mechanisms for at least 24 hours. Such long-lasting M1 CSE enhancement induced by a-tDCSUHCDS of M1-DLPFC could be a valuable finding in clinical scenarios such as learning, motor performance, or pain management.The present study has been registered on the Australian New Zealand Clinical Trial at http://www.anzctr.org.au/ with registry number of ACTRN12614000817640.

Anemia and Micronutrient Status of Women of Childbearing Age and Children 6–59 Months in the Democratic Republic of the Congo

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Sarah Harvey-Leeson

2016-02-01

Full Text Available Little is known about the micronutrient status of women and children in the Democratic Republic of the Congo, which is critical for the design of effective nutrition interventions. We recruited 744 mother-child pairs from South Kivu (SK and Kongo Central (KC. We determined hemoglobin (Hb, serum zinc, vitamin B12, folate, ferritin, soluble transferrin receptor (sTfR, retinol binding protein (RBP, C-reactive protein, and α-1 acid glycoprotein concentrations. Anemia prevalence was determined using Hb adjusted for altitude alone and Hb adjusted for both altitude and ethnicity. Anemia prevalence was lower after Hb adjustment for altitude and ethnicity, compared to only altitude, among women (6% vs. 17% in SK; 10% vs. 32% in KC, children 6–23 months (26% vs. 59% in SK; 25% vs. 42% in KC, and children 24–59 months (14% vs. 35% in SK; 23% vs. 44% in KC, respectively. Iron deficiency was seemingly higher with sTfR as compared to inflammation-adjusted ferritin among women (18% vs. 4% in SK; 21% vs. 5% in KC, children 6–23 months (51% vs. 14% in SK; 74% vs. 10% in KC, and children 24–59 months (23% vs. 4% in SK; 58% vs. 1% in KC. Regardless of indicator, iron deficiency anemia (IDA never exceeded 3% in women. In children, IDA reached almost 20% when sTfR was used but was only 10% with ferritin. Folate, B12, and vitamin A (RBP deficiencies were all very low (<5%; RBP was 10% in children. The prevalence of anemia was unexpectedly low. Inflammation-adjusted zinc deficiency was high among women (52% in SK; 58% in KC, children 6–23 months (23% in SK; 20% in KC, and children 24–59 months (25% in SK; 27% in KC. The rate of biochemical zinc deficiency among Congolese women and children requires attention.

Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity.

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Prado, Carolina; Contreras, Francisco; González, Hugo; Díaz, Pablo; Elgueta, Daniela; Barrientos, Magaly; Herrada, Andrés A; Lladser, Álvaro; Bernales, Sebastián; Pacheco, Rodrigo

2012-04-01

Dendritic cells (DCs) are responsible for priming T cells and for promoting their differentiation from naive T cells into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate T cell-mediated immunity. However, the involvement of specific neurotransmitters or receptors remains poorly understood. In this study, we analyzed the role of dopamine in the regulation of DC function. We found that DCs express dopamine receptors as well as the machinery necessary to synthesize, store, and degrade dopamine. Notably, the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and consequently attenuated the activation and proliferation of Ag-specific CD4(+) T cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the role of this receptor in the modulation of a CD4(+) T cell-driven autoimmunity model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type recipients were able to reduce the severity of experimental autoimmune encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed a significant reduction in the percentage of Th17 cells infiltrating the CNS without differences in the percentage of Th1 cells compared with animals transferred with wild-type DCs. Our findings demonstrate that by contributing to CD4(+) T cell activation and differentiation to Th17 phenotype, D5R expressed on DCs is able to modulate the development of an autoimmune response in vivo.

Evaluation of the effectiveness of transcranial direct current stimulation (tDCS) and psychosensory stimulation through DOCS scale in a minimally conscious subject.

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Dimitri, Danilo; De Filippis, Daniela; Galetto, Valentina; Zettin, Marina

2017-04-01

The aim of our study was to assess the effectiveness of transcranial direct current stimulation (tDCS) on alertness improvement in a patient in a minimally conscious state (MCS) by means of disorders of consciousness scale combined with psycho-sensory stimulation. The effects of tDCS on muscle hypertonia through the Ashworth scale were also examined. tDCS was performed through a two-channel intra-cephalic stimulator. After stimulation, the patient followed a psychosensory stimulation training. Results pointed out an increase in DOCunit score, as well as an increase in alertness maintenance and an improvement in muscle hypertonia, although a MCS state persisted.

The rehabilitative effects on written language of a combined language and parietal dual-tDCS treatment in a stroke case.

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De Tommaso, Barbara; Piedimonte, Alessandro; Caglio, Marcella M; D'Agata, Federico; Campagnoli, Marcello; Orsi, Laura; Raimondo, Simona; Vighetti, Sergio; Mortara, Paolo; Massazza, Giuseppe; Pinessi, Lorenzo

2017-09-01

In this paper we report the effect of a combined transcranial direct current stimulation (tDCS) and speech language therapy on linguistic deficits following left brain damage in a stroke case. We show that simultaneous electrical excitatory stimulation to the left and inhibitory stimulation to the right parietal regions (dual-tDCS) affected writing and reading rehabilitation, enhancing speech therapy outcomes. The results of a comparison with healthy controls showed that application of dual-tDCS could improve, in particular, sub-lexical transcoding and, specifically, the reading of non-words with increasing length and complexity. Positive repercussions on patient's quality of functional communication were also ascertained. Significant changes were also found in other language and cognitive tasks not directly treated (comprehension and constructive apraxia).

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

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Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

The effect of the interval-between-sessions on prefrontal transcranial direct current stimulation (tDCS) on cognitive outcomes: a systematic review and meta-analysis.

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Dedoncker, Josefien; Brunoni, Andre R; Baeken, Chris; Vanderhasselt, Marie-Anne

2016-10-01

Recently, there has been wide interest in the effects of transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) on cognitive functioning. However, many methodological questions remain unanswered. One of them is whether the time interval between active and sham-controlled stimulation sessions, i.e. the interval between sessions (IBS), influences DLPFC tDCS effects on cognitive functioning. Therefore, a systematic review and meta-analysis was performed of experimental studies published in PubMed, Science Direct, and other databases from the first data available to February 2016. Single session sham-controlled within-subject studies reporting the effects of tDCS of the DLPFC on cognitive functioning in healthy controls and neuropsychiatric patients were included. Cognitive tasks were categorized in tasks assessing memory, attention, and executive functioning. Evaluation of 188 trials showed that anodal vs. sham tDCS significantly decreased response times and increased accuracy, and specifically for the executive functioning tasks, in a sample of healthy participants and neuropsychiatric patients (although a slightly different pattern of improvement was found in analyses for both samples separately). The effects of cathodal vs. sham tDCS (45 trials), on the other hand, were not significant. IBS ranged from less than 1 h to up to 1 week (i.e. cathodal tDCS) or 2 weeks (i.e. anodal tDCS). This IBS length had no influence on the estimated effect size when performing a meta-regression of IBS on reaction time and accuracy outcomes in all three cognitive categories, both for anodal and cathodal stimulation. Practical recommendations and limitations of the study are further discussed.

Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

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Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

2016-10-01

Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

Probing neural mechanisms underlying auditory stream segregation in humans by transcranial direct current stimulation (tDCS).

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Deike, Susann; Deliano, Matthias; Brechmann, André

2016-10-01

One hypothesis concerning the neural underpinnings of auditory streaming states that frequency tuning of tonotopically organized neurons in primary auditory fields in combination with physiological forward suppression is necessary for the separation of representations of high-frequency A and low-frequency B tones. The extent of spatial overlap between the tonotopic activations of A and B tones is thought to underlie the perceptual organization of streaming sequences into one coherent or two separate streams. The present study attempts to interfere with these mechanisms by transcranial direct current stimulation (tDCS) and to probe behavioral outcomes reflecting the perception of ABAB streaming sequences. We hypothesized that tDCS by modulating cortical excitability causes a change in the separateness of the representations of A and B tones, which leads to a change in the proportions of one-stream and two-stream percepts. To test this, 22 subjects were presented with ambiguous ABAB sequences of three different frequency separations (∆F) and had to decide on their current percept after receiving sham, anodal, or cathodal tDCS over the left auditory cortex. We could confirm our hypothesis at the most ambiguous ∆F condition of 6 semitones. For anodal compared with sham and cathodal stimulation, we found a significant decrease in the proportion of two-stream perception and an increase in the proportion of one-stream perception. The results demonstrate the feasibility of using tDCS to probe mechanisms underlying auditory streaming through the use of various behavioral measures. Moreover, this approach allows one to probe the functions of auditory regions and their interactions with other processing stages. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cathodal transcranial direct current stimulation (tDCS) applied to the left premotor cortex (PMC) stabilizes a newly learned motor sequence.

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Focke, Jan; Kemmet, Sylvia; Krause, Vanessa; Keitel, Ariane; Pollok, Bettina

2017-01-01

While the primary motor cortex (M1) is involved in the acquisition the premotor cortex (PMC) has been related to over-night consolidation of a newly learned motor skill. The present study aims at investigating the possible contribution of the left PMC for the stabilization of a motor sequence immediately after acquisition as determined by susceptibility to interference. Thirty six healthy volunteers received anodal, cathodal and sham transcranial direct current stimulation (tDCS) to the left PMC either immediately prior to or during training on a serial reaction time task (SRTT) with the right hand. TDCS was applied for 10min, respectively. Reaction times were measured prior to training (t1), at the end of training (t2), and after presentation of an interfering random pattern (t3). Beyond interference from learning, the random pattern served as control condition in order to estimate general effects of tDCS on reaction times. TDCS applied during SRTT training did not result in any significant effects neither on acquisition nor on susceptibility to interference. In contrast to this, tDCS prior to SRTT training yielded an unspecific facilitation of reaction times at t2 independent of tDCS polarity. At t3, reduced susceptibility to interference was found following cathodal stimulation. The results suggest the involvement of the PMC in early consolidation and reveal a piece of evidence for the hypothesis that behavioral tDCS effects vary with the activation state of the stimulated area. Copyright © 2016. Published by Elsevier B.V.

High-definition transcranial direct current stimulation (HD-tDCS) of left dorsolateral prefrontal cortex affects performance in Balloon Analogue Risk Task (BART).

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Guo, Heng; Zhang, Zhuoran; Da, Shu; Sheng, Xiaotian; Zhang, Xichao

2018-02-01

Studies on risk preferences have long been of great concern and have examined the neural basis underlying risk-based decision making. However, studies using conventional transcranial direct current stimulation (tDCS) revealed that bilateral stimulation could change risk propensity with limited evidence of precisely focalized unilateral high-definition transcranial direct current stimulation (HD-tDCS). The aim of this experiment was to investigate the effect of HD-tDCS focalizing the left dorsal lateral prefrontal cortex (DLPFC) on risk-taking behavior during the Balloon Analogue Risk Task (BART). This study was designed as a between-subject, single-blind, sham-controlled experiment. University students were randomly assigned to three groups: the anodal group (F3 anode, AF3, F1, F5, FC3 returned), the cathodal group (F3 cathodal, AF3, F1, F5, FC3 returned) and the sham group. Subsequently, 1.5-mA 20-min HD-tDCS was applied during the BART, and the Positive Affect and Negative Affect Scale (PANAS), the Sensation Seeking Scale-5 (SSS-5), and the Behavioral Inhibition System and Behavioral Approach System scale (BIS/BAS) were measured as control variables. The cathodal group earned less total money than the sham group, and no significant difference was observed between the anodal group and the sham group. These results showed that, to some extent, focalized unilateral cathodal HD-tDCS on left DLPFC could change performance during risky tasks and diminish risky decision making. Further studies are needed to investigate the dose effect and electrode distribution of HD-tDCS during risky tasks and examine synchronous brain activity to show the neural basis.

Full-length Dysferlin Transfer by the Hyperactive Sleeping Beauty Transposase Restores Dysferlin-deficient Muscle

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Helena Escobar

2016-01-01

Full Text Available Dysferlin-deficient muscular dystrophy is a progressive disease characterized by muscle weakness and wasting for which there is no treatment. It is caused by mutations in DYSF, a large, multiexonic gene that forms a coding sequence of 6.2 kb. Sleeping Beauty (SB transposon is a nonviral gene transfer vector, already used in clinical trials. The hyperactive SB system consists of a transposon DNA sequence and a transposase protein, SB100X, that can integrate DNA over 10 kb into the target genome. We constructed an SB transposon-based vector to deliver full-length human DYSF cDNA into dysferlin-deficient H2K A/J myoblasts. We demonstrate proper dysferlin expression as well as highly efficient engraftment (>1,100 donor-derived fibers of the engineered myoblasts in the skeletal muscle of dysferlin- and immunodeficient B6. Cg-Dysfprmd Prkdcscid/J (Scid/BLA/J mice. Nonviral gene delivery of full-length human dysferlin into muscle cells, along with a successful and efficient transplantation into skeletal muscle are important advances towards successful gene therapy of dysferlin-deficient muscular dystrophy.

Analysis of the interaction between human RITA and Drosophila Suppressor of Hairless.

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Brockmann, Birgit; Mastel, Helena; Oswald, Franz; Maier, Dieter

2014-12-01

Notch signalling mediates intercellular communication, which is effected by the transcription factor CSL, an acronym for vertebrate CBF1/RBP-J, Drosophila Suppressor of Hairless [Su(H)] and C. elegans Lag1. Nuclear import of CBF1/RBP-J depends on co-activators and co-repressors, whereas the export relies on RITA. RITA is a tubulin and CBF1/RBP-J binding protein acting as a negative regulator of Notch signalling in vertebrates. RITA protein is highly conserved in eumatazoa, but no Drosophila homologue was yet identified. In this work, the activity of human RITA in the fly was addressed. To this end, we generated transgenic flies that allow a tissue specific induction of human RITA, which was demonstrated by Western blotting and in fly tissues. Unexpectedly, overexpression of RITA during fly development had little phenotypic consequences, even when overexpressed simultaneously with either Su(H) or the Notch antagonist Hairless. We demonstrate the in vivo binding of human RITA to Su(H) and to tubulin by co-immune precipitation. Moreover, RITA and tubulin co-localized to some degree in several Drosophila tissues. Overall our data show that human RITA, albeit binding to Drosophila Su(H) and tubulin, cannot influence the Notch signalling pathway in the fly, suggesting that a nuclear export mechanism of Su(H), if existent in Drosophila, does not depend on RITA. © 2015 The Authors.

Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy

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2014-01-01

Background Repetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas. Methods Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later. Results Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients. Conclusions This report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard. PMID:24479694

Effects of a common transcranial direct current stimulation (tDCS) protocol on motor evoked potentials found to be highly variable within individuals over 9 testing sessions.

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Horvath, Jared Cooney; Vogrin, Simon J; Carter, Olivia; Cook, Mark J; Forte, Jason D

2016-09-01

Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode; 3 cathode; 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the individual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test-retest reliability [anode: ICC(2,1) = 0.062; cathode: ICC(2,1) = 0.055] and moderate sham test-retest reliability [ICC(2,1) = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level. In addition, no significant effects of tDCS on MEP amplitude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations.

Cathodal Transcranial Direct Current Stimulation (tDCS) to the Right Cerebellar Hemisphere Affects Motor Adaptation During Gait.

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Fernandez, Lara; Albein-Urios, Natalia; Kirkovski, Melissa; McGinley, Jennifer L; Murphy, Anna T; Hyde, Christian; Stokes, Mark A; Rinehart, Nicole J; Enticott, Peter G

2017-02-01

The cerebellum appears to play a key role in the development of internal rules that allow fast, predictive adjustments to novel stimuli. This is crucial for adaptive motor processes, such as those involved in walking, where cerebellar dysfunction has been found to increase variability in gait parameters. Motor adaptation is a process that results in a progressive reduction in errors as movements are adjusted to meet demands, and within the cerebellum, this seems to be localised primarily within the right hemisphere. To examine the role of the right cerebellar hemisphere in adaptive gait, cathodal transcranial direct current stimulation (tDCS) was administered to the right cerebellar hemisphere of 14 healthy adults in a randomised, double-blind, crossover study. Adaptation to a series of distinct spatial and temporal templates was assessed across tDCS condition via a pressure-sensitive gait mat (ProtoKinetics Zeno walkway), on which participants walked with an induced 'limp' at a non-preferred pace. Variability was assessed across key spatial-temporal gait parameters. It was hypothesised that cathodal tDCS to the right cerebellar hemisphere would disrupt adaptation to the templates, reflected in a failure to reduce variability following stimulation. In partial support, adaptation was disrupted following tDCS on one of the four spatial-temporal templates used. However, there was no evidence for general effects on either the spatial or temporal domain. This suggests, under specific conditions, a coupling of spatial and temporal processing in the right cerebellar hemisphere and highlights the potential importance of task complexity in cerebellar function.

Connectivity between Right Inferior Frontal Gyrus and Supplementary Motor Area Predicts After-Effects of Right Frontal Cathodal tDCS on Picture Naming Speed

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Rosso, Charlotte; Valabregue, R.; Arbizy, C.

2014-01-01

Background: Cathodal transcranial direct current stimulation (tDCS) of the right frontal cortex improves language abilities in post-stroke aphasic patients. Yet little is known about the effects of right frontal cathodal tDCS on normal language function. Objective/hypothesis: To explore the catho...

Thinking Cap Plus Thinking Zap: tDCS of Frontopolar Cortex Improves Creative Analogical Reasoning and Facilitates Conscious Augmentation of State Creativity in Verb Generation.

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Green, Adam E; Spiegel, Katherine A; Giangrande, Evan J; Weinberger, Adam B; Gallagher, Natalie M; Turkeltaub, Peter E

2017-04-01

Recent neuroimaging evidence indicates neural mechanisms that support transient improvements in creative performance (augmented state creativity) in response to cognitive interventions (creativity cueing). Separately, neural interventions via tDCS show encouraging potential for modulating neuronal function during creative performance. If cognitive and neural interventions are separately effective, can they be combined? Does state creativity augmentation represent "real" creativity, or do interventions simply yield divergence by diminishing meaningfulness/appropriateness? Can augmenting state creativity bolster creative reasoning that supports innovation, particularly analogical reasoning? To address these questions, we combined tDCS with creativity cueing. Testing a regionally specific hypothesis from neuroimaging, high-definition tDCS-targeted frontopolar cortex activity recently shown to predict state creativity augmentation. In a novel analogy finding task, participants under tDCS formulated substantially more creative analogical connections in a large matrix search space (creativity indexed via latent semantic analysis). Critically, increased analogical creativity was not due to diminished accuracy in discerning valid analogies, indicating "real" creativity rather than inappropriate divergence. A simpler relational creativity paradigm (modified verb generation) revealed a tDCS-by-cue interaction; tDCS further enhanced creativity cue-related increases in semantic distance. Findings point to the potential of noninvasive neuromodulation to enhance creative relational cognition, including augmentation of the deliberate effort to formulate connections between distant concepts. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

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Pripfl, Jürgen; Lamm, Claus

2015-02-01

Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

The Behavioral Effects of tDCS on Visual Search Performance Are Not Influenced by the Location of the Reference Electrode

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Amanda Ellison

2017-09-01

Full Text Available We investigated the role of reference electrode placement (ipsilateral v contralateral frontal pole on conjunction visual search task performance when the transcranial direct current stimulation (tDCS cathode is placed over right posterior parietal cortex (rPPC and over right frontal eye fields (rFEF, both of which have been shown to be causally involved in the processing of this task using TMS. This resulted in four experimental manipulations in which sham tDCS was applied in week one followed by active tDCS the following week. Another group received sham stimulation in both sessions to investigate practice effects over 1 week in this task. Results show that there is no difference between effects seen when the anode is placed ipsi or contralaterally. Cathodal stimulation of rPPC increased search times straight after stimulation similarly for ipsi and contralateral references. This finding does not extend to rFEF stimulation. However, for both sites and both montages, practice effects as seen in the sham/sham condition were negated. This can be taken as evidence that for this task, reference placement on either frontal pole is not important, but also that care needs to be taken when contextualizing tDCS “effects” that may not be immediately apparent particularly in between-participant designs.

tDCS combined with optokinetic drift reduces egocentric neglect in severely impaired post-acute patients.

Science.gov (United States)

Turgut, Nergiz; Miranda, Marcela; Kastrup, Andreas; Eling, Paul; Hildebrandt, Helmut

2018-06-01

Visuospatial neglect is a disabling syndrome resulting in impaired activities of daily living and in longer durations of inpatient rehabilitation. Effective interventions to remediate neglect are still needed. The combination of tDCS and an optokinetic task might qualify as a treatment method. A total of 32 post-acute patients with left (n = 20) or right-sided neglect were allotted to an intervention or a control group (both groups n = 16). The intervention group received eight sessions of 1.5-2.0 mA parietal transcranial direct current stimulation (tDCS) during the performance of an optokinetic task distributed over two weeks. Additionally they received standard therapy for five hours per day. The control group received only the standard therapy. Patients were examined twice before (with 3-4 days between examinations) and twice after treatment (5-6 days between examinations). Compared to the control group and controlling for spontaneous remission, the intervention group improved on spontaneous body orientation and the Clock Drawing Test. Intragroup comparisons showed broad improvements on egocentric but not on allocentric symptoms only for the intervention group. A short additional application of tDCS during an optokinetic task led to improvements of severe neglect compared to a standard neurological early rehabilitation treatment. Improvements seem to concern primarily egocentric rather than allocentric neglect.

Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells

DEFF Research Database (Denmark)

Björkman, Andrea; Qvist, Per; Du, Likun

2015-01-01

of long microhomologies was found at recombination junctions derived from E3 ubiquitin-protein ligase RNF168-deficient, Fanconi anemia group J protein (FACJ, BRIP1)-deficient, or DNA endonuclease RBBP8 (CtIP)-compromised cells, whereas an increased frequency of S-region inversions was observed in breast...

Spared Primary Motor Cortex and the Presence of MEP in Cerebral Palsy Dictate the Responsiveness to tDCS During Gait Training

Directory of Open Access Journals (Sweden)

Luanda Collange Grecco

2016-07-01

Full Text Available The current priority of investigations involving transcranial direct current stimulation (tDCS and neurorehabilitation is to identify biomarkers associated with the positive results of the interventions such that respondent and non-respondent patients can be identified in the early phases of treatment. The aims were to determine whether; 1 present motor evoked potential (MEP and, 2 injuries involving the primary motor cortex, are associated with tDCS-enhancement in functional outcome following gait training in children with cerebral palsy (CP. We reviewed the data from our parallel, randomized, sham-controlled, double-blind studies. Fifty-six children with spastic CP received gait training (either treadmill training or virtual reality training and tDCS (active or sham. Univariate and multivariate logistic regression analyses were employed to identify clinical, neurophysiologic and neuroanatomic predictors associated with the responsiveness to treatment with tDCS. MEP presence during the initial evaluation and the subcortical injury were associated with positive effects in the functional results. The logistic regression revealed that present MEP was a significant predictor for the six-minute walk test (p=0.003 and gait speed (p=0.028, whereas the subcortical injury was a significant predictor of gait kinematics (p=0.013 and gross motor function (p = 0.021. In this preliminary study involving children with CP, two important prediction factors of good responses to anodal tDCS combined with gait training were identified. Apparently, MEP (integrity of the corticospinal tract and subcortical location of the brain injury exerted different influences on aspects related to gait, such as velocity and kinematics.

Unimpaired dendritic cell functions in MVP/LRP knockout mice.

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Mossink, Marieke H; de Groot, Jan; van Zon, Arend; Fränzel-Luiten, Erna; Schoester, Martijn; Scheffer, George L; Sonneveld, Pieter; Scheper, Rik J; Wiemer, Erik A C

2003-09-01

Dendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T- and B-cell-mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human DCs. To further investigate the role of vaults in DCs, we examined the effects of disruption of the major vault protein (MVP/LRP) on the development and antigen-presenting capacity of DCs, using our MVP/LRP knockout mouse model. Mononuclear bone marrow cells were isolated from wild-type and knockout mice and stimulated to differentiate to DCs. Like human DCs, the wild-type murine DC cultures strongly expressed MVP/LRP. Nevertheless, the MVP/LRP-deficient DCs developed normally and showed similar expression levels of several DC surface markers. No differences were observed in in vitro studies on the antigen uptake and presenting capacities of the wild-type and MVP/LRP knockout DCs. Moreover, immunization of the MVP/LRP-deficient mice with several T-cell antigens led to responses similar to those observed in the wild-type mice, indicating that the in vivo DC migration and antigen-presentation capacities are intact. Moreover, no differences were observed in the induction of the T cell-dependent humoral responses and orally induced peripheral T-cell tolerance. In conclusion, vaults are not required for primary DC functions. Their abundance in DCs may, however, still reflect basic roles in myeloid cell proliferation and DC development.

Using Transcranial tDCS to test cognitive hypotheses

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Nazbanou Nozari

2014-04-01

Full Text Available Transcranial Direct Current Stimulation (tDCS is used increasingly often for testing cognitive hypotheses. It is, however, often ignored that many assumptions regarding how the neural tissue reacts to stimulation have only been verified in the motor domain. Extrapolating these assumptions to the cognitive domain has a set of unique issues which, if ignored, can lead to incorrect interpretations. In this talk I will review a number of common pitfalls in using tDCS for testing a cognitive hypothesis, and discuss some solutions for better-controlled designs. I will address the following issues: 1- Making an incorrect assumption about the nature of the effect: It is often assumed that anodal stimulation has “excitatory” and cathodal stimulation has “inhibitory” effects. Results are then interpreted in light of this assumption. Obviously, if the assumption is incorrect, the interpretation of the results too will be incorrect. I will discuss how the effects of polarity can change as a function of a number of design parameters, and the dangers of making a priori assumptions about the direction of stimulation effects, especially when employing a new design. 2- Choosing an inappropriate montage: By definition, tDCS requires two electrodes, although we are often only interested in stimulating one brain region. Where the second (reference electrode is placed may not be of theoretical interest to us, but it can have serious consequences for our effects of interest. For one thing the path of the direct current changes as a function of where the reference electrode is placed. This affects the density of the current, as well as the regions that undergo stimulation. Moreover, the region directly under the reference electrode is very likely to be affected by stimulation. Therefore, sometimes the changes in behavior may be due to the unanticipated effects at the reference electrode site, as opposed to the hypothesized effects at the target electrode site

The impact of transcranial direct current stimulation (tDCS) combined with modified constraint-induced movement therapy (mCIMT) on upper limb function in chronic stroke: a double-blind randomized controlled trial.

Science.gov (United States)

Rocha, Sérgio; Silva, Evelyn; Foerster, Águida; Wiesiolek, Carine; Chagas, Anna Paula; Machado, Giselle; Baltar, Adriana; Monte-Silva, Katia

2016-01-01

This pilot double-blind sham-controlled randomized trial aimed to determine if the addition of anodal tDCS on the affected hemisphere or cathodal tDCS on unaffected hemisphere to modified constraint-induced movement therapy (mCIMT) would be superior to constraints therapy alone in improving upper limb function in chronic stroke patients. Twenty-one patients with chronic stroke were randomly assigned to receive 12 sessions of either (i) anodal, (ii) cathodal or (iii) sham tDCS combined with mCIMT. Fugl-Meyer assessment (FMA), motor activity log scale (MAL), and handgrip strength were analyzed before, immediately, and 1 month (follow-up) after the treatment. Minimal clinically important difference (mCID) was defined as an increase of ≥5.25 in the upper limb FMA. An increase in the FMA scores between the baseline and post-intervention and follow-up for active tDCS group was observed, whereas no difference was observed in the sham group. At post-intervention and follow-up, when compared with the sham group, only the anodal tDCS group achieved an improvement in the FMA scores. ANOVA showed that all groups demonstrated similar improvement over time for MAL and handgrip strength. In the active tDCS groups, 7/7 (anodal tDCS) 5/7 (cathodal tDCS) of patients experienced mCID against 3/7 in the sham group. The results support the merit of association of mCIMT with brain stimulation to augment clinical gains in rehabilitation after stroke. However, the anodal tDCS seems to have greater impact than the cathodal tDCS in increasing the mCIMT effects on motor function of chronic stroke patients. The association of mCIMT with brain stimulation improves clinical gains in rehabilitation after stroke. The improvement in motor recovery (assessed by Fugl-Meyer scale) was only observed after anodal tDCS. The modulation of damaged hemisphere demonstrated greater improvements than the modulation of unaffected hemispheres.

DCS: A Case Study of Identification of Knowledge and Disposition Gaps Using Principles of Continuous Risk Management

Science.gov (United States)

Norcross, Jason; Steinberg, Susan; Kundrot, Craig; Charles, John

2011-01-01

The Human Research Program (HRP) is formulated around the program architecture of Evidence-Risk-Gap-Task-Deliverable. Review of accumulated evidence forms the basis for identification of high priority risks to human health and performance in space exploration. Gaps in knowledge or disposition are identified for each risk, and a portfolio of research tasks is developed to fill them. Deliverables from the tasks inform the evidence base with the ultimate goal of defining the level of risk and reducing it to an acceptable level. A comprehensive framework for gap identification, focus, and metrics has been developed based on principles of continuous risk management and clinical care. Research towards knowledge gaps improves understanding of the likelihood, consequence or timeframe of the risk. Disposition gaps include development of standards or requirements for risk acceptance, development of countermeasures or technology to mitigate the risk, and yearly technology assessment related to watching developments related to the risk. Standard concepts from clinical care: prevention, diagnosis, treatment, monitoring, rehabilitation, and surveillance, can be used to focus gaps dealing with risk mitigation. The research plan for the new HRP Risk of Decompression Sickness (DCS) used the framework to identify one disposition gap related to establishment of a DCS standard for acceptable risk, two knowledge gaps related to DCS phenomenon and mission attributes, and three mitigation gaps focused on prediction, prevention, and new technology watch. These gaps were organized in this manner primarily based on target for closure and ease of organizing interim metrics so that gap status could be quantified. Additional considerations for the knowledge gaps were that one was highly design reference mission specific and the other gap was focused on DCS phenomenon.

Anodal tDCS Over the Left DLPFC Did Not Affect the Encoding and Retrieval of Verbal Declarative Information

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Gabriel A. de Lara

2017-08-01

Full Text Available Several studies imply that anodal transcranial direct current stimulation (tDCS over the left dorsolateral prefrontal cortex (DLPFC can modulate the formation of verbal episodic memories. The aim of this study was to test if tDCS through a multi-electrode Laplacian montage over the left DLPFC could differentially modulate declarative memory performance depending on the application phase. Two groups of healthy participants (n = 2 × 15 received 1 mA anodal or sham stimulation for 20 min during the encoding or during the recall phase on a delayed cued-recall, using a randomized, double-blinded, repeated-measures experimental design. Memory performance was assessed at two time points: 10 min and 24 h after learning. We found no significant difference between anodal and sham stimulation with regard to the memory scores between conditions (stimulation during encoding or recall or between time points, suggesting that anodal tDCS over the left DLPFC with these stimulation parameters had no effect on the encoding and the consolidation of associative verbal content.

Controlling the Anchoring Effect through Transcranial Direct Current Stimulation (tDCS to the Right Dorsolateral Prefrontal Cortex

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Jianbiao Li

2017-06-01

Full Text Available Selective accessibility mechanisms indicate that anchoring effects are results of selective retrieval of working memory. Neuroimaging studies have revealed that the right dorsolateral prefrontal cortex (DLPFC is closely related to memory retrieval and performance. However, no research has investigated the effect of changing the cortical excitability in right DLPFC on anchoring effects. Transcranial direct current stimulation (tDCS can modulate the excitability of the human cerebral cortex, while anodal and cathodal tDCS are postulated to increase or decrease cortical activity, respectively. In this study, we used tDCS to investigate whether effects of increased or decreased right DLPFC excitability influence anchoring effects in willingness to pay (WTP experiments. Ninety participants were first randomly assigned to receive either anodal, cathodal, or sham stimulation of 15 min, then they performed a valuation task regarding WTP. The results showed that anchoring effects were negatively related to activities of right DLPFC: the anodal stimulation diminished anchoring effects while the cathodal stimulation increased anchoring effects. These outcomes provide one of the first instances of neural evidence for the role of the right DLPFC in anchoring effects and support psychological explanations of the selective accessibility mechanisms and cognitive sets.

Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: A systematic review.

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Horvath, Jared Cooney; Forte, Jason D; Carter, Olivia

2015-01-01

Transcranial direct current stimulation (tDCS) is a form of neuromodulation that is increasingly being utilized to examine and modify a number of cognitive and behavioral measures. The theoretical mechanisms by which tDCS generates these changes are predicated upon a rather large neurophysiological literature. However, a robust systematic review of this neurophysiological data has not yet been undertaken. tDCS data in healthy adults (18-50) from every neurophysiological outcome measure reported by at least two different research groups in the literature was collected. When possible, data was pooled and quantitatively analyzed to assess significance. When pooling was not possible, data was qualitatively compared to assess reliability. Of the 30 neurophysiological outcome measures reported by at least two different research groups, tDCS was found to have a reliable effect on only one: MEP amplitude. Interestingly, the magnitude of this effect has been significantly decreasing over the last 14 years. Our systematic review does not support the idea that tDCS has a reliable neurophysiological effect beyond MEP amplitude modulation - though important limitations of this review (and conclusion) are discussed. This work raises questions concerning the mechanistic foundations and general efficacy of this device - the implications of which extend to the steadily increasing tDCS psychological literature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prognostic Importance of Vitamins A, E and Retinol-binding Protein 4 in Renal Cell Carcinoma Patients.

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Sobotka, Roman; Čapoun, Otakar; Kalousová, Marta; Hanuš, Tomáš; Zima, Tomáš; Koštířová, Milada; Soukup, Viktor

2017-07-01

To assess the prognostic importance of serum levels of retinol, retinol-binding protein 4 (RBP4) and vitamin E at the time of diagnosis in patients with renal cell carcinoma (RCC). In this prospective study, in a cohort of 102 renal cell carcinoma patients, relationships between serum levels of the aforementioned markers and recurrence-free survival (RFS), overall survival (OS), as well as cancer-specific survival (CSS), were evaluated. The vitamin A and vitamin E levels were determined by high-performance liquid chromatography (HPLC), while the RBP4 level by enzyme-linked immunosorbent assay (ELISA). The median follow-up period was 39 months. Renal cell carcinoma recurred in 9 patients; 23 patients died with 12 of them from RCC. The preoperative vitamin E level was associated to RFS (p=0.02). We found a significant relationship between OS and the level of RBP4 (p=0.002), retinol (p=0.037) and vitamin E (p=0.007). The CSS period was significantly associated with the level of RBP4 (p=0.0001) and retinol (p=0.0003). Patients with an RBP4 level less than 21.0 mg/l at the time of diagnosis had a 13.5-times higher risk of death due to RCC progression; this risk was up to 7.7-times higher with vitamin A levels under 0.52 mg/l. Low levels of vitamin A, E and RBP4 at the time of RCC diagnosis are associated with a poorer prognosis after surgery. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Immune Deficiency Disease' of Undetermined Aetiology in Infancy

African Journals Online (AJOL)

1974-04-06

Apr 6, 1974 ... J., 48, 687 (1974). Immune deficiency diseases in infancy are best known as ... tion at the age of 10 months confirmed the mental retarda- tion, and on further ... Examination of other organ systems was non-contributory. Triple .... linked recessive transmitted disease, and has not been re- ported in females.

Deficiency in plasmacytoid dendritic cells and type I interferon signalling prevents diet-induced obesity and insulin resistance in mice.

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Hannibal, Tine D; Schmidt-Christensen, Anja; Nilsson, Julia; Fransén-Pettersson, Nina; Hansen, Lisbeth; Holmberg, Dan

2017-10-01

Obesity is associated with glucose intolerance and insulin resistance and is closely linked to the increasing prevalence of type 2 diabetes. In mouse models of diet-induced obesity (DIO) and type 2 diabetes, an increased fat intake results in adipose tissue expansion and the secretion of proinflammatory cytokines. The innate immune system not only plays a crucial role in obesity-associated chronic low-grade inflammation but it is also proposed to play a role in modulating energy metabolism. However, little is known about how the modulation of metabolism by the immune system may promote increased adiposity in the early stages of increased dietary intake. Here we aimed to define the role of type I IFNs in DIO and insulin resistance. Mice lacking the receptor for IFN-α (IFNAR -/- ) and deficient in plasmacytoid dendritic cells (pDCs) (B6.E2-2 fl/fl .Itgax-cre) were fed a diet with a high fat content or normal chow. The mice were analysed in vivo and in vitro using cellular, biochemical and molecular approaches. We found that the development of obesity was inhibited by an inability to respond to type I IFNs. Furthermore, the development of obesity and insulin resistance in this model was associated with pDC recruitment to the fatty tissues and liver of obese mice (a 4.3-fold and 2.7-fold increase, respectively). Finally, we demonstrated that the depletion of pDCs protects mice from DIO and from developing obesity-associated metabolic complications. Our results provide genetic evidence that pDCs, via type I IFNs, regulate energy metabolism and promote the development of obesity.

Cerebellum as a forward but not inverse model in visuomotor adaptation task: a tDCS-based and modeling study.

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Yavari, Fatemeh; Mahdavi, Shirin; Towhidkhah, Farzad; Ahmadi-Pajouh, Mohammad-Ali; Ekhtiari, Hamed; Darainy, Mohammad

2016-04-01

Despite several pieces of evidence, which suggest that the human brain employs internal models for motor control and learning, the location of these models in the brain is not yet clear. In this study, we used transcranial direct current stimulation (tDCS) to manipulate right cerebellar function, while subjects adapt to a visuomotor task. We investigated the effect of this manipulation on the internal forward and inverse models by measuring two kinds of behavior: generalization of training in one direction to neighboring directions (as a proxy for inverse models) and localization of the hand position after movement without visual feedback (as a proxy for forward model). The experimental results showed no effect of cerebellar tDCS on generalization, but significant effect on localization. These observations support the idea that the cerebellum is a possible brain region for internal forward, but not inverse model formation. We also used a realistic human head model to calculate current density distribution in the brain. The result of this model confirmed the passage of current through the cerebellum. Moreover, to further explain some observed experimental results, we modeled the visuomotor adaptation process with the help of a biologically inspired method known as population coding. The effect of tDCS was also incorporated in the model. The results of this modeling study closely match our experimental data and provide further evidence in line with the idea that tDCS manipulates FM's function in the cerebellum.

Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

Science.gov (United States)

2014-07-01

include: 1) Listeria infection, including that mediated by attenuated strains, induces moDC, DDC , and LC maturation and activation. 2) Listeria...2f) Flow cytometry analysis of DCs for co-stimulatory and maturation markers (months 3-12) Result/status: Listeria-treated DDC -IDCs and LCs were...for moDCs, infection of DDC -IDCs and LCs with wild-type, LLO-deficient, and ActA- deficient Listeria induces the activation and maturation of DDC

Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study

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Xiaolan Yang

2017-08-01

Full Text Available Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC and the orbital frontal cortex (OFC play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS device to modulate the activity of participants’ DLPFC and OFC separately, comparing the causal relationships between people’s behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre–post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants’ preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants’ preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity.

Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study.

Science.gov (United States)

Yang, Xiaolan; Gao, Mei; Shi, Jinchuan; Ye, Hang; Chen, Shu

2017-01-01

Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the orbital frontal cortex (OFC) play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS) device to modulate the activity of participants' DLPFC and OFC separately, comparing the causal relationships between people's behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre-post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants' preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants' preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity.

Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Distress Tolerance: A Preliminary Study.

Science.gov (United States)

Mariano, Timothy Y; van't Wout, Mascha; Jacobson, Benjamin L; Garnaat, Sarah L; Kirschner, Jason L; Rasmussen, Steven A; Greenberg, Benjamin D

2015-08-01

Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P tDCS (P = 0.072). Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. Wiley Periodicals, Inc.

Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

Directory of Open Access Journals (Sweden)

Norihisa Mikami

Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition.

Directory of Open Access Journals (Sweden)

Chin-Tong Ong

2008-07-01

Full Text Available Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4(+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4(+ T or reporter cells, the presence of Lunatic Fringe in CD4(+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4(+ T cells lacking gamma-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation.

Enhancing decision-making and cognitive impulse control with transcranial direct current stimulation (tDCS) applied over the orbitofrontal cortex (OFC): A randomized and sham-controlled exploratory study.

Science.gov (United States)

Ouellet, Julien; McGirr, Alexander; Van den Eynde, Frederique; Jollant, Fabrice; Lepage, Martin; Berlim, Marcelo T

2015-10-01

Decision-making and impulse control (both cognitive and motor) are complex interrelated processes which rely on a distributed neural network that includes multiple cortical and subcortical regions. Among them, the orbitofrontal cortex (OFC) seems to be particularly relevant as demonstrated by several neuropsychological and neuroimaging investigations. In the present study we assessed whether transcranial direct current stimulation (tDCS) applied bilaterally over the OFC is able to modulate decision-making and cognitive impulse control. More specifically, 45 healthy subjects were randomized to receive a single 30-min session of active or sham anodal tDCS (1.5 mA) applied over either the left or the right OFC (coupled with contralateral cathodal tDCS). They were also assessed pre- and post-tDCS with a battery of computerized tasks. Our results show that participants who received active anodal tDCS (irrespective of laterality), vs. those who received sham tDCS, displayed more advantageous decision-making (i.e., increased Iowa Gambling Task "net scores" [p = 0.04]), as well as improved cognitive impulse control (i.e., decreased "interference" in the Stroop Word-Colour Task [p = 0.007]). However, we did not observe tDCS-related effects on mood (assessed by visual analogue scales), attentional levels (assessed by the Continuous Performance Task) or motor impulse control (assessed by the Stop-Signal Task). Our study potentially serves as a key translational step towards the development of novel non-invasive neuromodulation-based therapeutic interventions directly targeting vulnerability factors for psychiatric conditions such as suicidal behaviour and addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells.

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Michelle A Favila

2015-12-01

Full Text Available Leishmania major infection induces robust interleukin-12 (IL12 production in human dendritic cells (hDC, ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG and other phosphoglycan-containing molecules (PGs, making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS responsible for IL12 induction.Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-, or generally deficient for all PGs, (FV1 lpg2-. Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB and Interferon Regulatory Factor (IRF mediated transcription.These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12.

Boosting Memory by tDCS to Frontal or Parietal Brain Regions? A Study of the Enactment Effect Shows No Effects for Immediate and Delayed Recognition

Directory of Open Access Journals (Sweden)

Beat Meier

2018-06-01

Full Text Available Boosting memory with transcranial direct current stimulation (tDCS seems to be an elegant way to optimize learning. Here we tested whether tDCS to the left dorsolateral prefrontal cortex or to the left posterior parietal cortex would boost recognition memory in general and/or particularly for action phrases enacted at study. During study, 48 young adults either read or enacted simple action phrases. Memory for the action phrases was assessed after a retention interval of 45 min and again after 7-days to investigate the long-term consequences of brain stimulation. The results showed a robust enactment effect in both test sessions. Moreover, the decrease in performance was more pronounced for reading than for enacting the phrases at study. However, tDCS did not reveal any effect on subsequent recognition memory performance. We conclude that memory benefits of tDCS are not easily replicated. In contrast, enactment at study reliably boosts subsequent memory.

The Effectiveness of Transcranial Direct Current Stimulation (tDCS on Working Memory in Patients with Major Depression

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Mahboube Ebadi

2017-08-01

Full Text Available Abstract Background: The aim of this study was to evaluate the effectiveness of of transcranial direct current stimulation (tDCS on working memory in patients with major depression. Materials and Methods: The research method was quasi-experimental with pretest and post-test and follow-up with control group. The research population comprised female outpatient referrals to private psychiatric centers and psychological counseling centers in Tehran in the first half of 2016, They had received a diagnosis of depression by a psychiatrist at least once. Of these, 30 females were selected as a sample group with convenience sampling method and based on the criteria of inclusion and exclusion and were divided randomly into two groups , experimental (n = 15 and control (n = 15 group. The experimental group received transcranial direct current stimulation (tDCS in 10 sessions, While this intervention was not provided to the control group. The data were collected by N-BACK. Analysis of variance with repeated measurments was used to test the research hypothesis. Results: The results showed that transcranial direct current stimulation (tDCS had a significant effect on increasing working memory and the impact will continue to follow up. Conclusion: Therefore, this approach can be used to improve working memory in people with major depression.

DCS (Digital Control System) application of three generations; Aplicacao de um SDCD (Sistemas Digitais de Controle Distribuido) de tres geracoes

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Coelho, Celso Roberto Molinaro [PETROBRAS S.A., Sao Jose dos Campos, SP (Brazil). Refinaria Henrique Lage (REVAP)

2004-07-01

Digital Control System are three generations of hardware and software platforms in process automation , but DCS is using the same functions and presents the reliability and availability . The challenge in automation has to maintain the old and the newest system operating and integrated perhaps the different times of platforms to guarantee the actual investments and in the future. A new generation of DCS using field equipment to control or the actual architecture with a lot of new information are coming with the technologies. (author)

Neurocognitive Effects of Transcranial Direct Current Stimulation in Arithmetic Learning and Performance: A Simultaneous tDCS-fMRI Study.

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Hauser, Tobias U; Rütsche, Bruno; Wurmitzer, Karoline; Brem, Silvia; Ruff, Christian C; Grabner, Roland H

A small but increasing number of studies suggest that non-invasive brain stimulation by means of transcranial direct current stimulation (tDCS) can modulate arithmetic processes that are essential for higher-order mathematical skills and that are impaired in dyscalculic individuals. However, little is known about the neural mechanisms underlying such stimulation effects, and whether they are specific to cognitive processes involved in different arithmetic tasks. We addressed these questions by applying tDCS during simultaneous functional magnetic resonance imaging (fMRI) while participants were solving two types of complex subtraction problems: repeated problems, relying on arithmetic fact learning and problem-solving by fact retrieval, and novel problems, requiring calculation procedures. Twenty participants receiving left parietal anodal plus right frontal cathodal stimulation were compared with 20 participants in a sham condition. We found a strong cognitive and neural dissociation between repeated and novel problems. Repeated problems were solved more accurately and elicited increased activity in the bilateral angular gyri and medial plus lateral prefrontal cortices. Solving novel problems, in contrast, was accompanied by stronger activation in the bilateral intraparietal sulci and the dorsomedial prefrontal cortex. Most importantly, tDCS decreased the activation of the right inferior frontal cortex while solving novel (compared to repeated) problems, suggesting that the cathodal stimulation rendered this region unable to respond to the task-specific cognitive demand. The present study revealed that tDCS during arithmetic problem-solving can modulate the neural activity in proximity to the electrodes specifically when the current demands lead to an engagement of this area. Copyright © 2016 Elsevier Inc. All rights reserved.

CD11c controls herpes simplex virus 1 responses to limit virus replication during primary infection.

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Allen, Sariah J; Mott, Kevin R; Chentoufi, Aziz A; BenMohamed, Lbachir; Wechsler, Steven L; Ballantyne, Christie M; Ghiasi, Homayon

2011-10-01

CD11c is expressed on the surface of dendritic cells (DCs) and is one of the main markers for identification of DCs. DCs are the effectors of central innate immune responses, but they also affect acquired immune responses to infection. However, how DCs influence the efficacy of adaptive immunity is poorly understood. Here, we show that CD11c(+) DCs negatively orchestrate both adaptive and innate immunity against herpes simplex virus type 1 (HSV-1) ocular infection. The effectiveness and quantity of virus-specific CD8(+) T cell responses are increased in CD11c-deficient animals. In addition, the levels of CD83, CD11b, alpha interferon (IFN-α), and IFN-β, but not IFN-γ, were significantly increased in CD11c-deficient animals. Higher levels of IFN-α, IFN-β, and CD8(+) T cells in the CD11c-deficient mice may have contributed to lower virus replication in the eye and trigeminal ganglia (TG) during the early period of infection than in wild-type mice. However, the absence of CD11c did not influence survival, severity of eye disease, or latency. Our studies provide for the first time evidence that CD11c expression may abrogate the ability to reduce primary virus replication in the eye and TG via higher activities of type 1 interferon and CD8(+) T cell responses.

Effects of repeated anodal tDCS coupled with cognitive training for patients with severe traumatic brain injury: a pilot randomized controlled trial.

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Leśniak, Marcin; Polanowska, Katarzyna; Seniów, Joanna; Członkowska, Anna

2014-01-01

To determine whether cumulative anodal transcranial direct current stimulation (A-tDCS) of the left dorsolateral prefrontal cortex (DLPFC) could enhance rehabilitation of memory and attention in patients with traumatic brain injury (TBI). Inpatient and outpatient neurorehabilitation unit. Twenty-three adult patients, 4- to 92- months post severe TBI. Participants were randomly allocated to 2 groups. The experimental group received A-tDCS (10 minutes; 1 mA; in the DLPFC), followed by rehabilitative cognitive training, daily for 15 days. Controls received A-tDCS for 25 seconds (sham condition) with the same rehabilitation. Battery of memory and attention tests, which included visual and auditory modalities. Participants were tested twice before beginning rehabilitation (to control for spontaneous recovery), after rehabilitation completion, and 4 months later. Tests scores in both groups were similar at 3 weeks before and immediately before treatment. After treatment, the experimental group exhibited larger effect sizes in 6 of 8 cognitive outcome measures, but they were not significantly different from controls. At follow-up, differences remained insignificant. In contrast to previous studies, our study did not provide sufficient evidence to support the efficacy of repeated A-tDCS for enhancing rehabilitation of memory and attention in patients after severe TBI.

Effects of transcranial direct current stimulation (tDCS) on pain distress tolerance: a preliminary study

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Mariano, Timothy Y.; Wout, Mascha van’t; Jacobson, Benjamin L.; Garnaat, Sarah L.; Kirschner, Jason L.; Rasmussen, Steven A.; Greenberg, Benjamin D.

2015-01-01

Objective Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal (“inhibitory”) stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli versus anodal stimulation. Methods Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Results Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal versus anodal stimulation (p = 0.055) for participants self-completing the task. Pressure algometer (p = 0.81) and breath holding tolerance (p = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all p Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both p pain ratings tended to rise less after cathodal versus anodal tDCS (p = 0.072). Conclusions Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. PMID:26115372

Attenuated Heart Rate Response is Associated with Hypocretin Deficiency in Patients with Narcolepsy

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Sørensen, Gertrud Laura; Knudsen, Stine; Petersen, Eva Rosa

2013-01-01

Our results show that autonomic dysfunction is part of the narcoleptic phenotype, and that hypocretin-1 deficiency is the primary predictor of this dysfunction. This finding suggests that the hypocretin system participates in the modulation of cardiovascular function at rest. CITATION: Sorensen GL......; Knudsen S; Petersen ER; Kempfner J; Gammeltoft S; Sorensen HBD; Jennum P. Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy. SLEEP 2013;36(1):91-98....

Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke.

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Elsner, Bernhard; Kugler, Joachim; Pohl, Marcus; Mehrholz, Jan

2013-11-15

Stroke is one of the leading causes of disability worldwide. Functional impairment resulting in poor performance in activities of daily living (ADLs) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance and function after stroke, but a possible adjunct to stroke rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability and hence to improve ADL performance and function. To assess the effects of tDCS on generic activities of daily living (ADLs) and motor function in people with stroke. We searched the Cochrane Stroke Group Trials Register (March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2013), MEDLINE (1948 to May 2013), EMBASE (1980 to May 2013), CINAHL (1982 to May 2013), AMED (1985 to May 2013), Science Citation Index (1899 to May 2013) and four additional databases. In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials (from which we analysed only the first period as a parallel-group design) that compared tDCS versus control in adults with stroke for improving ADL performance and function. Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. We included 15 studies involving a total of 455 participants. Analysis of six studies involving 326 participants regarding our primary outcome, ADL, showed no evidence of an effect in favour of tDCS at the end of the intervention phase (mean difference (MD) 5.31 Barthel

The HLT, DAQ and DCS TDR

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Wickens, F. J

At the end of June the Trigger-DAQ community achieved a major milestone with the submission to the LHCC of the Technical Design Report (TDR) for DAQ, HLT and DCS. The first unbound copies were handed to the LHCC referees on the scheduled date of 30th June, this was followed a few days later by a limited print run which produced the first bound copies (see Figure 1). As had previously been announced both to the LHCC and the ATLAS Collaboration it was not possible on this timescale to give a complete validation of all of the aspects of the architecture in the TDR. So it had been agreed that further work would continue over the summer to provide more complete results for the formal review by the LHCC of the TDR in September. Thus there followed an intense programme of measurements and analysis: especially to provide results for HLT both in testbeds and for the event selection software itself; to provide additional information on scaling of the dataflow aspects; to provide first results on the new prototype ROBin...

Facilitation of Function and Manipulation Knowledge of Tools Using Transcranial Direct Current Stimulation (tDCS

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Ryo Ishibashi

2018-01-01

Full Text Available Using a variety of tools is a common and essential component of modern human life. Patients with brain damage or neurological disorders frequently have cognitive deficits in their recognition and manipulation of tools. In this study, we focused on improving tool-related cognition using transcranial direct current stimulation (tDCS. Converging evidence from neuropsychology, neuroimaging and non- invasive brain stimulation has identified the anterior temporal lobe (ATL and inferior parietal lobule (IPL as brain regions supporting action semantics. We observed enhanced performance in tool cognition with anodal tDCS over ATL and IPL in two cognitive tasks that require rapid access to semantic knowledge about the function or manipulation of common tools. ATL stimulation improved access to both function and manipulation knowledge of tools. The effect of IPL stimulation showed a trend toward better manipulation judgments. Our findings support previous studies of tool semantics and provide a novel approach for manipulation of underlying circuits.

Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs?

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de Aguiar, Vania; Bastiaanse, Roelien; Capasso, Rita; Gandolfi, Marialuisa; Smania, Nicola; Rossi, Giorgio; Miceli, Gabriele

2015-01-01

Background: Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance

PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

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Dongxia Ma

Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

Effects of anodal transcranial direct current stimulation (tDCS) on behavioral and spatial memory during the early stage of traumatic brain injury in the rats.

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Yoon, Kyung Jae; Lee, Yong-Taek; Chae, Seoung Wan; Park, Chae Ri; Kim, Dae Yul

2016-03-15

Transcranial direct current stimulation (tDCS) is a noninvasive technique to modulate the neural membrane potential. Its effects in the early stage of traumatic brain injury (TBI) have rarely been investigated. This study assessed the effects of anodal tDCS on behavioral and spatial memory in a rat model of traumatic brain injury. Thirty six rats underwent lateral fluid percussion and were then randomly assigned to one of three groups: control (n=12), five-day tDCS over peri-lesional cortex at one (1W, n=12), or two (2W, n=12) weeks post-injury. The Barnes maze (BM) and Rotarod (RR) tests were evaluated in a blind manner on day 1, week 3 and week 5 post-injury. After three weeks, both the 1W and 2W groups showed significant improvements in the BM ratio (PtDCS ameliorated behavioral and spatial memory function in the early phase after TBI when it is delivered two weeks post-injury. Earlier stimulation (one week post-injury) improves spatial memory only. However, the beneficial effects did not persist after cessation of the anodal stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice.

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Jesus Gil-Pulido

Full Text Available Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3 is required for the development of classical CD8α+ and CD103+ DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr-/--deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α+ and CD103+ antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis.

Recurrent themes in the history of the home use of electrical stimulation: Transcranial direct current stimulation (tDCS) and the medical battery (1870-1920).

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Wexler, Anna

In recent years, neuroscientists and ethicists have warned of the dangers of the unsupervised home use of transcranial direct current stimulation (tDCS), in which individuals stimulate their own brains with low levels of electricity for self-improvement purposes. Although the home use of tDCS is often referred to as a novel phenomenon, in reality the late nineteenth and early twentieth century saw a proliferation of electrical stimulation devices for home use. In particular, the use of an object known as the medical battery bears a number of striking similarities to the modern-day use of tDCS. This article reviews a number of features thought to be unique to the present day home use of brain stimulation, with a particular focus on analogies between tDCS and the medical battery. Archival research was conducted at the Bakken Museum and at the American Medical Association's Historical Health Fraud Archives. Many of the features characterizing the contemporary home use tDCS-a do-it-yourself (DIY) movement, anti-medical establishment themes, conflicts between lay and professional usage-are a repetition of themes that occurred a century ago with regard to the medical battery. A number of features, however, seem to be unique to the present, such as the dominant discourse about risk and safety, the division between cranial and non-cranial stimulation, and utilization for cognitive enhancement purposes. Viewed in the long durée, the contemporary use of electrical stimulation at home is not a novel phenomenon, but rather the latest wave in a series of ongoing attempts by lay individuals to utilize electricity for therapeutic purposes. Copyright © 2016 Elsevier Inc. All rights reserved.

Storage Pool Deficiencies

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... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice.

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Huo, Feifei; Li, Dongbei; Zhao, Bo; Luo, Yadong; Zhao, Bingjie; Zou, Xueyang; Li, Yi; Yang, Wei

2018-02-01

As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis. To determine the role of Aire in maintaining immune tolerance by bone marrow-derived dendritic cells (BMDCs), in the present study we utilized Aire-knockout mice to examine the changes of maturation status and TRAs expression on BMDCs, additionally investigate the differentiation of CD4 + T cells. The results showed that expression of costimulatory molecule and major histocompatibility complex class II (MHC-II) molecule was increased and expression of various TRAs was decreased in BMDCs from Aire-knockout mice. Aire deficiency reduced the differentiation of naïve CD4 + T cells into type 2T helper (Th2) cells and regulatory T cells (Tregs) but enhanced the differentiation of naïve CD4 + T cells into Th1 cells, Th17 cells, and follicular helper T (Tfh) cells. The results demonstrate that Aire expressed by BMDCs plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.

Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury.

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Volarevic, Vladislav; Markovic, Bojana Simovic; Bojic, Sanja; Stojanovic, Maja; Nilsson, Ulf; Leffler, Hakon; Besra, Gurdyal S; Arsenijevic, Nebojsa; Paunovic, Verica; Trajkovic, Vladimir; Lukic, Miodrag L

2015-02-01

Galectin-3 (Gal-3), an endogenous lectin, exhibits pro- and anti-inflammatory effects in various disease conditions. In order to explore the role of Gal-3 in NKT-cell-dependent pathology, we induced hepatitis in C57BL/6 WT and Gal-3-deficient mice by using specific ligand for NKT cells: α-galactosylceramide, glycolipid Ag presented by CD1d. The injection of α-galactosylceramide significantly enhanced expression of Gal-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal-3 (induced by Gal-3-inhibitor TD139) abrogated the susceptibility to NKT-cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12) and their production by liver DCs and NKT cells were also downregulated. Genetic deletion or selective inhibition of Gal-3 alleviated influx of inflammatory CD11c(+) CD11b(+) DCs in the liver and favored tolerogenic phenotype and IL-10 production of liver NKT and DCs. Deletion of Gal-3 attenuated the capacity of DCs to support liver damage in the passive transfer experiments and to produce pro-inflammatory cytokines in vitro. Gal-3-deficient DCs failed to optimally stimulate production of pro-inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, Gal-3 regulates the capacity of DCs to support NKT-cell-mediated liver injury, playing an important pro-inflammatory role in acute liver injury. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Left prefrontal neuronavigated electrode localization in tDCS : 10–20 EEG system versus MRI-guided neuronavigation

NARCIS (Netherlands)

De Witte, Sara; Klooster, Debby; Dedoncker, Josefien; Duprat, Romain; Remue, Jonathan; Baeken, Chris

2018-01-01

Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral

Cooperation Not Competition: Bihemispheric tDCS and fMRI Show Role for Ipsilateral Hemisphere in Motor Learning.

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Waters, Sheena; Wiestler, Tobias; Diedrichsen, Jörn

2017-08-02

What is the role of ipsilateral motor and premotor areas in motor learning? One view is that ipsilateral activity suppresses contralateral motor cortex and, accordingly, that inhibiting ipsilateral regions can improve motor learning. Alternatively, the ipsilateral motor cortex may play an active role in the control and/or learning of unilateral hand movements. We approached this question by applying double-blind bihemispheric transcranial direct current stimulation (tDCS) over both contralateral and ipsilateral motor cortex in a between-group design during 4 d of unimanual explicit sequence training in human participants. Independently of whether the anode was placed over contralateral or ipsilateral motor cortex, bihemispheric stimulation yielded substantial performance gains relative to unihemispheric or sham stimulation. This performance advantage appeared to be supported by plastic changes in both hemispheres. First, we found that behavioral advantages generalized strongly to the untrained hand, suggesting that tDCS strengthened effector-independent representations. Second, functional imaging during speed-matched execution of trained sequences conducted 48 h after training revealed sustained, polarity-independent increases in activity in both motor cortices relative to the sham group. These results suggest a cooperative rather than competitive interaction of the two motor cortices during skill learning and suggest that bihemispheric brain stimulation during unimanual skill learning may be beneficial because it harnesses plasticity in the ipsilateral hemisphere. SIGNIFICANCE STATEMENT Many neurorehabilitation approaches are based on the idea that is beneficial to boost excitability in the contralateral hemisphere while attenuating that of the ipsilateral cortex to reduce interhemispheric inhibition. We observed that bihemispheric transcranial direct current stimulation (tDCS) with the excitatory anode either over contralateral or ipsilateral motor cortex

PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal transcranial direct current stimulation (tDCS) in major depressive disorder-study design and methodology of a multicenter double-blind randomized placebo-controlled trial.

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Bajbouj, Malek; Aust, Sabine; Spies, Jan; Herrera-Melendez, Ana-Lucia; Mayer, Sarah V; Peters, Maike; Plewnia, Christian; Fallgatter, Andreas J; Frase, Lukas; Normann, Claus; Behler, Nora; Wulf, Linda; Brakemeier, Eva-Lotta; Padberg, Frank

2017-12-06

Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. About 20-30% of patients do not respond to the standard psychopharmacological and/or psychotherapeutic interventions. Mounting evidence from neuroimaging studies in MDD patients reveal altered activation patterns in lateral prefrontal brain areas. Successful cognitive behavioral therapy (CBT) is associated with a recovery of these neural alterations. Moreover, it has been demonstrated that transcranial direct current stimulation (tDCS) is capable of influencing prefrontal cortex activity and cognitive functions such as working memory and emotion regulation. Thus, a clinical trial investigating the effects of an antidepressant intervention combining CBT with tDCS seems promising. The present study investigates the antidepressant efficacy of a combined CBT-tDCS intervention as compared to CBT with sham-tDCS or CBT alone. A total of 192 patients (age range 20-65 years) with MDD (Hamilton Depression Rating Scale Score ≥ 15, 21-item version) will be recruited at four study sites across Germany (Berlin, Munich, Tuebingen, and Freiburg) and randomly assigned to one of the following three treatment arms: (1) CBT + active tDCS; (2) CBT + sham-tDCS; and (3) CBT alone. All participants will attend a 6-week psychotherapeutic intervention comprising 12 sessions of CBT each lasting 100 min in a closed group setting. tDCS will be applied simultaneously with CBT. Active tDCS includes stimulation with an intensity of 2 mA for 30 min with the anode placed over F3 and the cathode over F4 according to the EEG 10-20 system, if assigned. The primary outcome measure is the change in Montgomery-Åsberg Depression Rating Scale scores from baseline to 6, 18, and 30 weeks after the first session. Participants also undergo pre- and post-treatment neuropsychological testing and functional magnetic resonance imaging (fMRI) to assess changes in prefrontal functioning and connectivity

Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons.

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Karten, Barbara; Vance, Dennis E; Campenot, Robert B; Vance, Jean E

2003-02-07

Niemann Pick type C (NPC) disease is a progressive neurodegenerative disorder. In cells lacking functional NPC1 protein, endocytosed cholesterol accumulates in late endosomes/lysosomes. We utilized primary neuronal cultures in which cell bodies and distal axons reside in separate compartments to investigate the requirement of NPC1 protein for transport of cholesterol from cell bodies to distal axons. We have recently observed that in NPC1-deficient neurons compared with wild-type neurons, cholesterol accumulates in cell bodies but is reduced in distal axons (Karten, B., Vance, D. E., Campenot, R. B., and Vance, J. E. (2002) J. Neurochem. 83, 1154-1163). We now show that NPC1 protein is expressed in both cell bodies and distal axons. In NPC1-deficient neurons, cholesterol delivered to cell bodies from low density lipoproteins (LDLs), high density lipoproteins, or cyclodextrin complexes was transported into axons in normal amounts, whereas transport of endogenously synthesized cholesterol was impaired. Inhibition of cholesterol synthesis with pravastatin in wild-type and NPC1-deficient neurons reduced axonal growth. However, LDLs restored a normal rate of growth to wild-type but not NPC1-deficient neurons treated with pravastatin. Thus, although LDL cholesterol is transported into axons of NPC1-deficient neurons, this source of cholesterol does not sustain normal axonal growth. Over the lifespan of NPC1-deficient neurons, these defects in cholesterol transport might be responsible for the observed altered distribution of cholesterol between cell bodies and axons and, consequently, might contribute to the neurological dysfunction in NPC disease.

Single-session tDCS over the dominant hemisphere affects contralateral spectral EEG power, but does not enhance neurofeedback-guided event-related desynchronization of the non-dominant hemisphere's sensorimotor rhythm.

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Mondini, Valeria; Mangia, Anna Lisa; Cappello, Angelo

2018-01-01

Transcranial direct current stimulation (tDCS) and neurofeedback-guided motor imagery (MI) have attracted considerable interest in neurorehabilitation, given their ability to influence neuroplasticity. As tDCS has been shown to modulate event-related desynchronization (ERD), the neural signature of motor imagery detected for neurofeedback, a combination of the techniques was recently proposed. One limitation of this approach is that the area targeted for stimulation is the same from which the signal for neurofeedback is acquired. As tDCS may interfere with proximal electroencephalographic (EEG) electrodes, in this study our aim was to test whether contralateral tDCS could have interhemispheric effects on the spectral power of the unstimulated hemisphere, possibly mediated by transcallosal connection, and whether such effects could be used to enhance ERD magnitudes. A contralateral stimulation approach would indeed facilitate co-registration, as the stimulation electrode would be far from the recording sites. Twenty right-handed healthy volunteers (aged 21 to 32) participated in the study: ten assigned to cathodal, ten to anodal versus sham stimulation. We applied stimulation over the dominant (left) hemisphere, and assessed ERD and spectral power over the non-dominant (right) hemisphere. The effect of tDCS was evaluated over time. Spectral power was assessed in theta, alpha and beta bands, under both rest and MI conditions, while ERD was evaluated in alpha and beta bands. Two main findings emerged: (1) contralateral alpha-ERD was reduced after anodal (p = 0.0147), but not enhanced after cathodal tDCS; (2) both stimulations had remote effects on the spectral power of the contralateral hemisphere, particularly in theta and alpha (significant differences in the topographical t-value maps). The absence of contralateral cathodal ERD enhancement suggests that the protocol is not applicable in the context of MI training. Nevertheless, ERD results of anodal and spectral

Magnesium deficiency induces anxiety-and depression-like behavior and metabolic dysfunction in C57Bl/6J mice

DEFF Research Database (Denmark)

Winther, G.; Wang, T.; Singewald, N.

2012-01-01

) in mice through depression-and anxiety phenotyping experiments, namely the forced swim test and light-dark box respectively. We determined the behavioural effects 30 minutes after treatment with imipramine (20 mg/kg), diazepam (2 mg/kg) and ketamine (3 mg/kg). The glucose tolerance test was used to assess...... metabolic function in Mg deficient mice. Results: We found that, compared to control (n=10), mice receiving Mg deficient diet (n=10) (10 % RDA), were more immobile in the forced swim test....

Disturbing Reading: J.M. Coetzee's "The Problem of Evil"

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Tarc, Aparna Mishra

2011-01-01

A literary representation can give us grief. J.M. Coetzee's "The Problem of Evil" follows the crisis of reading of his main character Elizabeth Costello as she struggles to comprehend discursive images of evil. Costello's trouble with reading is not attributed to a cognitive deficiency in her ability to read the text but to a psychical…

Beta band transcranial alternating (tACS and direct current stimulation (tDCS applied after initial learning facilitate retrieval of a motor sequence

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Vanessa eKrause

2016-01-01

Full Text Available The primary motor cortex (M1 contributes to the acquisition and early consolidation of a motor sequence. Although the relevance of M1 excitability for motor learning has been supported, the significance of M1 oscillations remains an open issue. This study aims at investigating to what extent retrieval of a newly learned motor sequence can be differentially affected by motor-cortical transcranial alternating (tACS and direct current stimulation (tDCS. Alpha (10 Hz, beta (20 Hz or sham tACS was applied in 36 right-handers. Anodal or cathodal tDCS was applied in 30 right-handers. Participants learned an eight-digit serial reaction time task (SRTT; sequential vs. random with the right hand. Stimulation was applied to the left M1 after SRTT acquisition at rest for ten minutes. Reaction times were analyzed at baseline, end of acquisition, retrieval immediately after stimulation and reacquisition after eight further sequence repetitions.Reaction times during retrieval were significantly faster following 20 Hz tACS as compared to 10 Hz and sham tACS indicating a facilitation of early consolidation. TDCS yielded faster reaction times, too, independent of polarity. No significant differences between 20 Hz tACS and tDCS effects on retrieval were found suggesting that 20 Hz effects might be associated with altered motor-cortical excitability. Based on the behavioural modulation yielded by tACS and tDCS one might speculate that altered motor-cortical beta oscillations support early motor consolidation possibly associated with neuroplastic reorganization.

Effect of transcranial direct current stimulation (tDCS) over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial

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Shiozawa, Pedro; Gomes, July Silveira; Ducos, Daniella Valverde; Akiba, Henrique Teruo; Dias, Álvaro Machado; Trevizol, Alisson Paulino; Uchida, Ricardo R.; Orlov, Natasza; Cordeiro, Quirino

2016-01-01

Abstract Introduction: We report a transcranial direct current stimulation (tDCS) protocol over the dorsolateral prefrontal cortex (DLPFC) combined with cognitive training in schizophrenia. Method: We assessed psychotic symptoms in nine patients using the Positive and Negative Syndrome Scale (PANSS). All evaluations were scored at baseline, at the end of the intervention protocol, and during a 4-week follow-up. The tDCS protocol consisted of 10 consecutive sessions over 5-day periods. We pl...

miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice

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Fang Gao

2017-04-01

Full Text Available Summary: Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl, was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs into intermediate neural progenitors (INPs in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment. : In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP. Keywords: neural stem cells, intermediate neural progenitors, Notch, RBP-J, neuron, glia, miR-342-5p

Enhancing verbal creativity: modulating creativity by altering the balance between right and left inferior frontal gyrus with tDCS.

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Mayseless, N; Shamay-Tsoory, S G

2015-04-16

Creativity is the production of novel ideas that have value. Previous research indicated that while regions in the right hemisphere are implicated in the production of new ideas, damage to the left inferior frontal gyrus (IFG) is associated with increased creativity, indicating that the left IFG damage may have a "releasing" effect on creativity. To examine this, in the present study we used transcranial direct current stimulation (tDCS) to modulate activity of the right and the left IFG. In the first experiment we show that whereas anodal tDCS over the right IFG coupled with cathodal tDCS over the left IFG increases creativity as measured by a verbal divergent thinking task, the reverse stimulation does not affect creative production. To further confirm that only altering the balance between the two hemispheres is crucial in modulating creativity, in the second experiment we show that stimulation targeting separately the left IFG (cathodal stimulation) or the right IFG (anodal stimulation) did not result in changes in creativity as measured by verbal divergent thinking. These findings support the balance hypothesis, according to which verbal creativity requires a balance of activation between the right and the left frontal lobes, and more specifically, between the right and the left IFG. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth

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Roland El Ghazal

2016-05-01

Full Text Available In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1 in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4–deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.

Conventional dendritic cells at the crossroads between immunity and cholesterol homeostasis in atherosclerosis.

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Gautier, Emmanuel L; Huby, Thierry; Saint-Charles, Flora; Ouzilleau, Betty; Pirault, John; Deswaerte, Virginie; Ginhoux, Florent; Miller, Elizabeth R; Witztum, Joseph L; Chapman, M John; Lesnik, Philippe

2009-05-05

Immunoinflammatory mechanisms are implicated in the atherogenic process. The polarization of the immune response and the nature of the immune cells involved, however, are major determinants of the net effect, which may be either proatherogenic or antiatherogenic. Dendritic cells (DCs) are central to the regulation of immunity, the polarization of the immune response, and the induction of tolerance to antigens. The potential role of DCs in atherosclerosis, however, remains to be defined. We created a mouse model in which the lifespan and immunogenicity of conventional DCs are enhanced by specific overexpression of the antiapoptotic gene hBcl-2 under the control of the CD11c promoter. When studied in either low-density lipoprotein receptor-deficient or apolipoprotein E-deficient backgrounds, DC-hBcl2 mice exhibited an expanded DC population associated with enhanced T-cell activation, a T-helper 1 and T-helper 17 cytokine expression profile, and elevated production of T-helper 1-driven IgG2c autoantibodies directed against oxidation-specific epitopes. This proatherogenic signature, however, was not associated with acceleration of atherosclerotic plaque progression, because expansion of the DC population was unexpectedly associated with an atheroprotective decrease in plasma cholesterol levels. Conversely, depletion of DCs in hyperlipidemic CD11c-diphtheria toxin receptor/apolipoprotein E-deficient transgenic mice resulted in enhanced cholesterolemia, thereby arguing for a close relationship between the DC population and plasma cholesterol levels. Considered together, the present data reveal that conventional DCs are central to the atherosclerotic process, because they are directly implicated in both cholesterol homeostasis and the immune response.

High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.

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Shirai, Tomomi; Shichi, Yuta; Sato, Miyuki; Tanioka, Yuri; Furusho, Tadasu; Ota, Toru; Tadokoro, Tadahiro; Suzuki, Tsukasa; Kobayashi, Ken-Ichi; Yamamoto, Yuji

2016-03-01

Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P type 2 diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors.

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Bhattacharyya, Suchita; Zagórska, Anna; Lew, Erin D; Shrestha, Bimmi; Rothlin, Carla V; Naughton, John; Diamond, Michael S; Lemke, Greg; Young, John A T

2013-08-14

Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses that are elevated in comparison to wild-type cells. As a consequence, TAM-deficient DCs are relatively resistant to infection by flaviviruses and pseudotyped retroviruses, but infection can be restored with neutralizing type I IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of renal replacement therapy on retinol-binding protein 4 isoforms

DEFF Research Database (Denmark)

Frey, Simone K; Henze, Andrea; Nagl, Britta

2009-01-01

Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney dis...... diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms....

Combined brain Fe, Cu, Zn and neurometabolite analysis - a new methodology for unraveling the efficacy of transcranial direct current stimulation (tDCS) in appetite control.

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Ziomber, Agata; Surowka, Artur Dawid; Antkiewicz-Michaluk, Lucyna; Romanska, Irena; Wrobel, Pawel; Szczerbowska-Boruchowska, Magdalena

2018-03-01

Obesity is a chronic, multifactorial origin disease that has recently become one of the most frequent lifestyle disorders. Unfortunately, current obesity treatments seem to be ineffective. At present, transcranial direct current brain stimulation (tDCS) represents a promising novel treatment methodology that seems to be efficient, well-tolerated and safe for a patient. Unfortunately, the biochemical action of tDCS remains unknown, which prevents its widespread use in the clinical arena, although neurobiochemical changes in brain signaling and metal metabolism are frequently reported. Therefore, our research aimed at exploring the biochemical response to tDCS in situ, in the brain areas triggering feeding behavior in obese animals. The objective was to propose a novel neurochemical (serotoninergic and dopaminergic signaling) and trace metal analysis of Fe, Cu and Zn. In doing so, we used energy-dispersive X-ray fluorescence (EDXRF) and high-performance liquid chromatography (HPLC). Anodal-type stimulation (atDCS) of the right frontal cortex was utilized to down-regulate food intake and body weight gain in obese rats. EDXRF was coupled with the external standard method in order to quantify the chemical elements within appetite-triggering brain areas. Major dopamine metabolites were assessed in the brains, based on the HPLC assay utilizing the external standard assay. Our study confirms that elemental analysis by EDXRF and brain metabolite assay by HPLC can be considered as a useful tool for the in situ investigation of the interplay between neurochemical and Fe/Cu/Zn metabolism in the brain upon atDCS. With this methodology, an increase in both Cu and Zn in the satiety center of the stimulated group could be reported. In turn, the most significant neurochemical changes involved dopaminergic and serotoninergic signaling in the brain reward system.

Theories of inter-hemispheric interactions in aphasia: the role of tDCS in rehabilitation of post-stroke aphasia

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Roy H Hamilton

2014-04-01

Full Text Available Mounting data from behavioral and neuroimaging studies have shown that the process of recovery from aphasia is largely driven by the reorganization of brain networks related to language. Evidence implicates a variety of potential mechanisms in this reorganization, some of which involve substantive changes in brain functional activity within and between cerebral hemispheres. These changes include intrahemispheric recruitment of perilesional left-hemisphere regions and transcallosal interhemispheric interactions between lesioned left-hemisphere language areas and homologous regions in the right hemisphere. With respect to the role of the right hemisphere, it is debated whether interhemispheric interactions are beneficial or deleterious to recovering language networks. Recent years have also seen the emergence of noninvasive brain stimulation techniques such as transcranial magnetic stimulation (TMS and transcranial direct current stimulation (tDCS as potential novel treatments for post-stroke aphasia. Because these techniques are predicated on either focal excitation or inhibition of brain areas, characterization of the functional roles of the left and right hemispheres and transcallosal interactions in aphasia recovery is of central importance to the development and refinement of stimulation-based therapies. However, most treatment studies involving noninvasive brain stimulation in aphasia have tacitly accepted the interhemispheric inhibition model, in which right hemisphere activity interferes with language recovery that is mediated by left hemisphere perisylvian regions. Based on this account, many studies in aphasia involving TMS and tDCS have adopted one of two approaches consistent with the model: left hemisphere excitation or right hemisphere inhibition. In this presentation, we will review both clinical and cognitive neuroscience evidence that elucidates different hemispheric mechanisms that influence recovery from aphasia after stroke

Subcutaneous dissociative conscious sedation (sDCS an alternative method for airway regional blocks: a new approach

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Javid Mihan J

2011-10-01

Full Text Available Abstract Background Predicted difficult airway is a definite indication for awake intubation and spontaneous ventilation. Airway regional blocks which are commonly used to facilitate awake intubation are sometimes impossible or forbidden. On the other hand deep sedation could be life threatening in the case of compromised airway. The aim of this study is evaluating "Subcutaneous Dissociative Conscious Sedation" (sDCS as an alternative method to airway regional blocks for awake intubation. Methods In this prospective, non-randomized study, 30 patients with predicted difficult airway (laryngeal tumors, who were scheduled for direct laryngoscopic biopsy (DLB, underwent "Subcutaneous Dissociative Conscious Sedation" (sDCS exerted by intravenous fentanyl 3-4ug/kg and subcutaneous ketamine 0.6-0.7 mg/kg. The tongue and pharynx were anesthetized with lidocaine spray (4%. 10 minutes after a subcutaneous injection of ketamine direct laryngoscopy was performed. Extra doses of fentanyl 50-100 ug were administered if the patient wasn't cooperative enough for laryngoscopy. Patients were evaluated for hemodynamic stability (heart rate and blood pressure, oxygen saturation (Spo2, patient cooperation (obedient to open the mouth for laryngoscopy and the number of tries for laryngoscopy, patient comfort (remaining moveless, hallucination, nystagmus and salivation (need for aspiration before laryngoscopy. Results Direct laryngoscopy was performed successfully in all patients. One patient needed extra fentanyl and then laryngoscopy was performed successfully on the second try. All patients were cooperative enough during laryngoscopy. Hemodynamic changes more than 20% occurred in just one patient. Oxygen desaturation (spo2 Conclusions Subcutaneous Dissociative Conscious Sedation (sDCS as a new approach to airway is an acceptable and safe method for awake intubation and it can be suggested as a noninvasive substitute of low complication rate for regional airway

Cerebellar anodal tDCS increases implicit learning when strategic re-aiming is suppressed in sensorimotor adaptation.

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Leow, Li-Ann; Marinovic, Welber; Riek, Stephan; Carroll, Timothy J

2017-01-01

Neurophysiological and neuroimaging work suggests that the cerebellum is critically involved in sensorimotor adaptation. Changes in cerebellar function alter behaviour when compensating for sensorimotor perturbations, as shown by non-invasive stimulation of the cerebellum and studies involving patients with cerebellar degeneration. It is known, however, that behavioural responses to sensorimotor perturbations reflect both explicit processes (such as volitional aiming to one side of a target to counteract a rotation of visual feedback) and implicit, error-driven updating of sensorimotor maps. The contribution of the cerebellum to these explicit and implicit processes remains unclear. Here, we examined the role of the cerebellum in sensorimotor adaptation to a 30° rotation of visual feedback of hand position during target-reaching, when the capacity to use explicit processes was manipulated by controlling movement preparation times. Explicit re-aiming was suppressed in one condition by requiring subjects to initiate their movements within 300ms of target presentation, and permitted in another condition by requiring subjects to wait approximately 1050ms after target presentation before movement initiation. Similar to previous work, applying anodal transcranial direct current stimulation (tDCS; 1.5mA) to the right cerebellum during adaptation resulted in faster compensation for errors imposed by the rotation. After exposure to the rotation, we evaluated implicit remapping in no-feedback trials after providing participants with explicit knowledge that the rotation had been removed. Crucially, movements were more adapted in these no-feedback trials following cerebellar anodal tDCS than after sham stimulation in both long and short preparation groups. Thus, cerebellar anodal tDCS increased implicit remapping during sensorimotor adaptation, irrespective of preparation time constraints. The results are consistent with the possibility that the cerebellum contributes to the

Iodine Deficiency

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... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

Fibrinogen cleavage products and Toll-like receptor 4 promote the generation of programmed cell death 1 ligand 2-positive dendritic cells in allergic asthma.

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Cho, Minkyoung; Lee, Jeong-Eun; Lim, Hoyong; Shin, Hyun-Woo; Khalmuratova, Roza; Choi, Garam; Kim, Hyuk Soon; Choi, Wahn Soo; Park, Young-Jun; Shim, Inbo; Kim, Byung-Seok; Kang, Chang-Yuil; Kim, Jae-Ouk; Tanaka, Shinya; Kubo, Masato; Chung, Yeonseok

2017-10-14

Inhaled protease allergens preferentially trigger T H 2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on induction of T H 2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce T H 2-favorable DCs in the airway remains unclear. We sought to determine a subset of DCs responsible for T H 2 cell responses in allergic asthma and the mechanism by which protease allergens induce the DC subset in the airway. Mice were challenged intranasally with protease allergens or fibrinogen cleavage products (FCPs) to induce allergic airway inflammation. DCs isolated from mediastinal lymph nodes were analyzed for surface phenotype and T-cell stimulatory function. Anti-Thy1.2 and Mas-TRECK mice were used to deplete innate lymphoid cells and mast cells, respectively. Adoptive cell transfer, bone marrow DC culture, anti-IL-13, and Toll-like receptor (TLR) 4-deficient mice were used for further mechanistic studies. Protease allergens induced a remarkable accumulation of T H 2-favorable programmed cell death 1 ligand 2 (PD-L2) + DCs in mediastinal lymph nodes, which was significantly abolished in mice depleted of mast cells and, to a lesser extent, innate lymphoid cells. Mechanistically, FCPs generated by protease allergens triggered IL-13 production from wild-type mast cells but not from TLR4-deficient mast cells, which resulted in an increase in the number of PD-L2 + DCs. Intranasal administration of FCPs induced an increase in numbers of PD-L2 + DCs in the airway, which was significantly abolished in TLR4- and mast cell-deficient mice. Injection of IL-13 restored the PD-L2 + DC population in mice lacking mast cells. Our findings unveil the "protease-FCP-TLR4-mast cell-IL-13" axis as a molecular mechanism for generation of T H 2-favorable PD-L2 + DCs in allergic asthma and suggest that targeting the PD-L2 + DC pathway might be effective in suppressing allergic T-cell responses in the airway

Clearance of Giardia muris infection in mice deficient in natural killer cells.

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Heyworth, M F; Kung, J E; Eriksson, E C

1986-01-01

Immunocompetent C57BL/6J mice and beige mice (which are deficient in natural killer cells) were infected with Giardia muris. Both types of mice cleared G. muris infection at similar rates. This observation suggests that clearance of G. muris parasites from the mouse intestine is not mediated by natural killer cells.

Langerin-expressing dendritic cells in gut-associated lymphoid tissues.

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Chang, Sun-Young; Kweon, Mi-Na

2010-03-01

Dendritic cells (DCs) are key regulators of the immune system. They act as professional antigen-presenting cells and are capable of activating naive T cells and stimulating the growth and differentiation of B cells. According to their molecular expression, DCs can be divided into several subsets with different functions. We focus on DC subsets expressing langerin, a C-type lectin. Langerin expression is predominant in skin DCs, but langerin-expressing DCs also exist in mucosal tissue and can be induced by immunization and sometimes by nutrient deficiency. Topical transcutaneous immunization induces langerin(+)CD8 alpha(-) DCs in mesenteric lymph nodes (MLNs), which mediate the production of antigen-specific immunoglobulin A antibody in the intestine. Yet, in one recent study, langerin(+) DCs were generated in gut-associated lymphoid tissue and contributed to the suppressive intestinal immune environment in the absence of retinoic acid. In this review, we focus on the phenotypic and functional characteristics of langerin(+) DCs in the mucosal tissues, especially MLNs.

Neuromarkers of anxiety and depression in a patient after neuro-ophthalmic surgery of the meningioma – effect of individually-tailored tDCS and neurofeedback

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Andrzej Mirski

2015-12-01

Full Text Available The aim of the study was to evaluate the effectiveness of individually tailored anodal tDCs/ neurofeedback protocol for the reduction of post-operative depression after a neuroophtalmological operation of the meningioma. The neuromarkers in Quantitative EEG (QEEG and Event-related potentials (ERPs were utilized in the construction of protocol and evaluation. [b]Case description[/b]. A 45-year-old female after successful neuro-ophthalmic surgery of the meningioma, complained of severe pain and anxiety, difficulties with sleeping, attention and memory problems, as well as inability to continue working in her given profession. Neuropsychological testing showed lack of cognitive disturbances and post-operative depression. Two working hypotheses were tested to find neuromarkers of depression and anxiety. In line with the ‘depression hypothesis’ a frontal alpha asymmetry pattern was found in the patient, and in line with the ‘anxiety’ hypothesis an increased left temporal P1 wave in response to visual stimuli was found in ERPs. A specific alpha asymmetry neurofeedback protocol combined with an anodal tDCS was suggested. Twenty sessions of individually-tailored anodal tDCs/ neurofeedback protocol were performed. The QEEG frontal asymmetry pattern and the excessive temporal P1 wave were normalized after the intervention. [b]Conclusions. [/b]The patient recovered from post-operative depression and returned to work after 20 sessions of the combined neurofeedback/tDCS protocol. Specific patterns of QEEG and ERPs serve as neuromarkers for constructing the protocol and for monitoring the results of intervention.

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study.

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Abend, Rany; Sar-El, Roy; Gonen, Tal; Jalon, Itamar; Vaisvaser, Sharon; Bar-Haim, Yair; Hendler, Talma

2018-05-09

Implicit regulation of emotions involves medial-prefrontal cortex (mPFC) regions exerting regulatory control over limbic structures. Diminished regulation relates to aberrant mPFC functionality and psychopathology. Establishing means of modulating mPFC functionality could benefit research on emotion and its dysregulation. Here, we tested the capacity of transcranial direct current stimulation (tDCS) targeting mPFC to modulate subjective emotional states by facilitating implicit emotion regulation. Stimulation was applied concurrently with functional magnetic resonance imaging to validate its neurobehavioral effect. Sixteen participants were each scanned twice, counterbalancing active and sham tDCS application, while undergoing negative mood induction (clips featuring negative vs. neutral contents). Effects of stimulation on emotional experience were assessed using subjective and neural measures. Subjectively, active stimulation led to significant reduction in reported intensity of experienced emotions to negatively valenced (p = 0.005) clips but not to neutral clips (p > 0.99). Active stimulation further mitigated a rise in stress levels from pre- to post-induction (sham: p = 0.004; active: p = 0.15). Neurally, stimulation increased activation in mPFC regions associated with implicit emotion regulation (ventromedial-prefrontal cortex; subgenual anterior-cingulate cortex, sgACC), and in ventral striatum, a core limbic structure (all ps  0.64, ps < 0.018), suggesting individual differences in stimulation responsivity. Results of this study indicate the potential capacity of tDCS to facilitate brain activation in mPFC regions underlying implicit regulation of emotion and accordingly modulate subjective emotional experiences. © 2018 International Neuromodulation Society.

Iron-Deficiency Anemia

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Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells

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Yi-Gen Pan

2017-10-01

Full Text Available The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM-containing adapters DAP12 and FcεRI γ-chain (FcRγ has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs. Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes. In addition, increments of T cell activation and T helper 17 polarization induced by FcRγ-deficient DCs were observed both in vitro and in vivo. Examining the Dectin-1 signaling, we revealed that the activations of several signaling molecules were augmented in FcRγ-deficient DCs stimulated with Dectin-1 ligands. Furthermore, we demonstrated that the association of phosphatases SHP-1 and PTEN with FcRγ may contribute to the negative regulation of FcRγ in Dectin-1 activation in DCs. These results extend the inhibitory effect of ITAM-containing adapters to Dectin-1 response in immune functions, even though Dectin-1 contains an ITAM-like intracellular domain. According to the role of Dectin-1 in responding to microbes and tumor cells, our finding may have applications in the development of vaccine and cancer therapy.

Using Biophysical Models to Understand the Effect of tDCS on Neurorehabilitation: Searching for Optimal Covariates to Enhance Poststroke Recovery.

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Malerba, Paola; Straudi, Sofia; Fregni, Felipe; Bazhenov, Maxim; Basaglia, Nino

2017-01-01

Stroke is a leading cause of worldwide disability, and up to 75% of survivors suffer from some degree of arm paresis. Recently, rehabilitation of stroke patients has focused on recovering motor skills by taking advantage of use-dependent neuroplasticity, where high-repetition of goal-oriented movement is at times combined with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS). Merging the two approaches is thought to provide outlasting clinical gains, by enhancing synaptic plasticity and motor relearning in the motor cortex primary area. However, this general approach has shown mixed results across the stroke population. In particular, stroke location has been found to correlate with the likelihood of success, which suggests that different patients might require different protocols. Understanding how motor rehabilitation and stimulation interact with ongoing neural dynamics is crucial to optimize rehabilitation strategies, but it requires theoretical and computational models to consider the multiple levels at which this complex phenomenon operate. In this work, we argue that biophysical models of cortical dynamics are uniquely suited to address this problem. Specifically, biophysical models can predict treatment efficacy by introducing explicit variables and dynamics for damaged connections, changes in neural excitability, neurotransmitters, neuromodulators, plasticity mechanisms, and repetitive movement, which together can represent brain state, effect of incoming stimulus, and movement-induced activity. In this work, we hypothesize that effects of tDCS depend on ongoing neural activity and that tDCS effects on plasticity may be also related to enhancing inhibitory processes. We propose a model design for each step of this complex system, and highlight strengths and limitations of the different modeling choices within our approach. Our theoretical framework proposes a change in paradigm, where biophysical models can contribute

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

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Sahlem, Gregory L; Badran, Bashar W; Halford, Jonathan J; Williams, Nolan R; Korte, Jeffrey E; Leslie, Kimberly; Strachan, Martha; Breedlove, Jesse L; Runion, Jennifer; Bachman, David L; Uhde, Thomas W; Borckardt, Jeffery J; George, Mark S

2015-01-01

A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed

Evaluation of DCS III Transmission Alternatives. Phase 1A report. Appendix B. Regulatory Barriers.

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1980-05-26

Resolution DK). B.1.1.5 Importance of the RR in the DCS III Study. The ITU Radio Regulation offers a means to appraise viability of the alternatives to be...interference 466-1 483 Measurement of performance by means of signal 482 Measurement of noise in actual traffic 481 Table B.l-6. Communication Satellite...Economic and technical aspects of the choice of transmission systems GAS 5 Economic conditions and tel ecommunication development GAS 6 Economic and

The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.

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Wouter Beumer

Full Text Available Two major dendritic cell (DC subsets have been described in the pancreas of mice: The CD11c+ CD8α- DCs (strong CD4+ T cell proliferation inducers and the CD8α+ CD103+ DCs (T cell apoptosis inducers. Here we analyzed the larger subset of CD11c+ CD8α- DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR to elucidate abnormalities in underlying gene expression networks. CD11c+ CD8α- DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c+ CD8α- DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24 was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+ CD8α- DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhanced up-regulation of inflammatory genes was supported by the in vitro cytokine production profile of the DCs. In conclusion, our data show that NOD pancreatic CD11c+ CD8α- DCs show various deficiencies in steady state, while hyperreactive when encountering a danger signal such as LPS.

Iron-Deficiency Anemia

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... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction.

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Sparing, Roland; Mottaghy, Felix M

2008-04-01

Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

tDCS Stimulation of the dlPFC Selectively Moderates the Detrimental Impact of Emotion on Analytical Reasoning.

Science.gov (United States)

Trémolière, Bastien; Maheux-Caron, Véronique; Lepage, Jean-François; Blanchette, Isabelle

2018-01-01

There is evidence of a detrimental effect of emotion on reasoning. Recent studies suggest that this relationship is mediated by working memory, a function closely associated with the dorsolateral prefrontal cortex (dlPFC). Relying on transcranial direct current stimulation (tDCS), the present research explores the possibility that anodal stimulation of the dlPFC has the potential to prevent the effect of emotion on analytical reasoning. Thirty-four participants took part in a lab experiment and were tested twice: one session using offline anodal stimulation (with a 2 mA current stimulation applied to the left dlPFC for 20 min), one session using a control (sham) stimulation. In each session, participants solved syllogistic reasoning problems featuring neutral and emotionally negative contents. Results showed that anodal stimulation diminished the deleterious effect of emotion on syllogistic reasoning, but only for a subclass of problems: problems where the conclusion was logically valid. We discuss our results in the light of the reasoning literature as well as the apparent variability of tDCS effects.

Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis.

Science.gov (United States)

Maricic, Igor; Halder, Ramesh; Bischof, Felix; Kumar, Vipin

2014-08-01

CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139-151/I-A(s)-tetramer(+) cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

LHCb Silicon Tracker DAQ and DCS Online Systems

CERN Multimedia

Buechler, A; Rodriguez, P

2009-01-01

The LHCb experiment at the Large Hadron Collider (LHC) at CERN in Geneva Switzerland is specialized on precision measurements of b quark decays. The Silicon Tracker (ST) contributes a crucial part in tracking the particle trajectories and consists of two silicon micro-strip detectors, the Tracker Turicensis upstream of the LHCb magnet and the Inner Tracker downstream. The radiation and the magnetic field represent new challenges for the implementation of a Detector Control System (DCS) and the data acquisition (DAQ). The DAQ has to deal with more than 270K analog readout channels, 2K readout chips and real time DAQ at a rate of 1.1 MHz with data processing at TELL1 level. The TELL1 real time algorithms for clustering thresholds and other computations run on dedicated FPGAs that implement 13K configurable parameters per board, in total 1.17 K parameters for the ST. After data processing the total throughput amounts to about 6.4 Gbytes from an input data rate of around ~337 Gbytes per second. A finite state ma...

Latent Presentation of Decompression Sickness After Altitude Chamber Training in an Active Duty Flier.

Science.gov (United States)

Gentry, James; Rango, Juan; Zhang, Jianzhong; Biedermann, Shane

2017-04-01

Decompression sickness (DCS) is a potential danger and risk for both divers and aircrew alike. DCS is also a potential side effect of altitude (hypobaric) chamber training as well and can present long after training occurs. Literature review shows that altitude chamber induced DCS has approximately a 0.25% incidence. A 32-yr-old, active duty military member developed symptoms of DCS 3 h after his hypobaric chamber training. Unfortunately, he did not seek treatment for DCS until 48 h after the exposure. His initial treatment included ground level oxygen therapy for 30 min at 12 L of oxygen per minute using a nonrebreathing mask. He achieved complete symptom resolution and was returned to duty. However, 12 d after his initial Flight Medicine evaluation, the patient returned complaining of a right temporal headache, multijoint pains, and fatigue. He was treated in the hyperbaric chamber and had complete resolution of symptoms. He was returned to flying status and 5 mo later denied any return of symptoms. Hypobaric chamber familiarity training is a requirement for all military aircrew personnel to allow them assess their ability to identify symptoms of hypoxia. This training method is not only costly to maintain, but it also places aircrew and chamber technicians at risk for potential long-term side effects from failed recompression treatment of DCS. We are presenting a case of recurrent DCS symptoms 12 d after initial ground level oxygen therapy.Gentry J, Rango J, Zhang J, Biedermann S. Latent presentation of decompression sickness after altitude chamber training in an active duty flier. Aerosp Med Hum Perform. 2017; 88(4):427-430.

Projected shell model study of yrast states of neutron-deficient odd-mass Pr nuclei

International Nuclear Information System (INIS)

Ibanez-Sandoval, A.; Ortiz, M. E.; Velazquez, V.; Galindo-Uribarri, A.; Hess, P. O.; Sun, Y.

2011-01-01

A wide variety of modern instruments allow us to study neutron-deficient nuclei in the A=130 mass region. Highly deformed nuclei have been found in this region, providing opportunities to study the deformed rotational bands. The description of the 125,127,129,131,133 Pr isotopes with the projected shell model is presented in this paper. Good agreement between theory and experiment is obtained and some characteristics are discussed, including the dynamic moment of inertia J (2) , kinetic moment of inertia J (1) , the crossing of rotational bands, and backbending effects.

A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages

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Town Terrence

2009-05-01

Full Text Available Abstract Background Macrophages and dendritic cells (DCs play key roles in host defense against HSV-1 infection. Although macrophages and DCs can be infected by herpes simplex virus type 1 (HSV-1, both cell types are resistant to HSV-1 replication. The aim of our study was to determine factor (s that are involved in the resistance of DCs and macrophages to productive HSV-1 infection. Results We report here that, in contrast to bone marrow-derived DCs and macrophages from wild type mice, DCs and macrophages isolated from signal transducers and activators of transcription-1 deficient (STAT1-/- mice were susceptible to HSV-1 replication and the production of viral mRNAs and DNA. There were differences in expression of immediate early, early, and late gene transcripts between STAT1+/+ and STAT1-/- infected APCs. Conclusion These results suggest for the first time that the JAK-STAT1 pathway is involved in blocking replication of HSV-1 in DCs and macrophages.

A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages

Science.gov (United States)

Mott, Kevin R; UnderHill, David; Wechsler, Steven L; Town, Terrence; Ghiasi, Homayon

2009-01-01

Background Macrophages and dendritic cells (DCs) play key roles in host defense against HSV-1 infection. Although macrophages and DCs can be infected by herpes simplex virus type 1 (HSV-1), both cell types are resistant to HSV-1 replication. The aim of our study was to determine factor (s) that are involved in the resistance of DCs and macrophages to productive HSV-1 infection. Results We report here that, in contrast to bone marrow-derived DCs and macrophages from wild type mice, DCs and macrophages isolated from signal transducers and activators of transcription-1 deficient (STAT1-/-) mice were susceptible to HSV-1 replication and the production of viral mRNAs and DNA. There were differences in expression of immediate early, early, and late gene transcripts between STAT1+/+ and STAT1-/- infected APCs. Conclusion These results suggest for the first time that the JAK-STAT1 pathway is involved in blocking replication of HSV-1 in DCs and macrophages. PMID:19439086

Prevalence and risk factors of vitamin D deficiency in patients with widespread musculoskeletal pain

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Muharrem Çidem

2013-12-01

Full Text Available Objective: Vitamin D deficiency is a worldwide common health problems. Vitamin D deficiency in adults has been associated with proximal muscle weakness, skeletal mineralization defect, and an increased risk of falling. Patients with vitamin D deficiency commonly complain of widespread pain in the body. The aim of this study was to examine the prevalence and risk factors of 25-hydroxyvitamin D deficiency in patients complaining of widespread musculoskeletal pain. Methods: In this cross-sectional study, 8457 patients with widespread musculoskeletal pain (7772 females, 685 males, aged 46.7 (range 20-100 years were included. Serum 25-hydroxyvitamin D was measured with ELISA method. Patients were classified into two groups: 1 Patients with vitamin D deficiency (20 ng/ml. Results: Prevalence of vitamin D deficiency was found to be 71.7%. A binary logistic regression model showed that low 25(OHVit D level was associated with gender, age and month in which 25(OH hypovitaminosis was determined. The risk of low 25(OH Vit D was found to be 2.15 times higher in female patients and 1.52 times higher on March and 1.55 times higher on April. Conclusion: This study indicates that Vitamin D deficiency should be taken into consideration in patients with widespread musculoskeletal pain, and some precautions such as sunbathe during summer should be recommended patients having risk of vitamin D deficiency. J Clin Exp Invest 2013; 4 (4: 48-491

Consideration of Individual Brain Geometry and Anisotropy on the Effect of tDCS

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Mohsen Mosayebi Samani

2017-12-01

Full Text Available Introduction: The response variability between subjects, which is one of the fundamental challenges facing transcranial direct current stimulation (tDCS, can be investigated by understanding how the current is distributed through the brain. This understanding can be obtained by means of computational methods utilizing finite element (FE models. Materials and Methods: In this study, the effect of realistic geometry and white matter anisotropy on the head electrical current density intensity (CDI distribution was measured using a magnetic resonance imaging (MRI-derived FE model at the whole brain, below electrodes, and cellular levels. Results: The results revealed that on average, the real geometry changes the CDI in gray matter and the WM by 29% and 55%, respectively. In addition, WM anisotropy led to an 8% and 36% change of CDI across GM and WM, respectively. The results indicated that for this electrode configuration, the maximum CDI occurs not below the electrode, but somewhere between the electrodes, and its locus varies greatly between individuals.  In addition, by investigating the effect of current density components on cellular excitability, significant individual differences in the level of excitability were detected. Conclusion: Accordingly, consideration of the real geometry in computational modeling is vital. In addition, WM anisotropy does not significantly influence the CDI on the gray matter surface, however, it alters the CDI inside the brain; therefore, it can be taken into account, especially, when stimulation of brain’s internal regions is proposed. Finally, to predict the outcome result of tDCS, the examination of its effect at the cellular level is of great importance.

Optimization of focality and direction in dense electrode array transcranial direct current stimulation (tDCS)

Science.gov (United States)

Guler, Seyhmus; Dannhauer, Moritz; Erem, Burak; Macleod, Rob; Tucker, Don; Turovets, Sergei; Luu, Phan; Erdogmus, Deniz; Brooks, Dana H.

2016-06-01

Objective. Transcranial direct current stimulation (tDCS) aims to alter brain function non-invasively via electrodes placed on the scalp. Conventional tDCS uses two relatively large patch electrodes to deliver electrical current to the brain region of interest (ROI). Recent studies have shown that using dense arrays containing up to 512 smaller electrodes may increase the precision of targeting ROIs. However, this creates a need for methods to determine effective and safe stimulus patterns as the number of degrees of freedom is much higher with such arrays. Several approaches to this problem have appeared in the literature. In this paper, we describe a new method for calculating optimal electrode stimulus patterns for targeted and directional modulation in dense array tDCS which differs in some important aspects with methods reported to date. Approach. We optimize stimulus pattern of dense arrays with fixed electrode placement to maximize the current density in a particular direction in the ROI. We impose a flexible set of safety constraints on the current power in the brain, individual electrode currents, and total injected current, to protect subject safety. The proposed optimization problem is convex and thus efficiently solved using existing optimization software to find unique and globally optimal electrode stimulus patterns. Main results. Solutions for four anatomical ROIs based on a realistic head model are shown as exemplary results. To illustrate the differences between our approach and previously introduced methods, we compare our method with two of the other leading methods in the literature. We also report on extensive simulations that show the effect of the values chosen for each proposed safety constraint bound on the optimized stimulus patterns. Significance. The proposed optimization approach employs volume based ROIs, easily adapts to different sets of safety constraints, and takes negligible time to compute. An in-depth comparison study gives

Modulating transcallosal and intra-hemispheric brain connectivity with tDCS: Implications for interventions in Aphasia.

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Zheng, Xin; Dai, Weiying; Alsop, David C; Schlaug, Gottfried

2016-07-25

Transcranial direct current stimulation (tDCS) can enhance or diminish cortical excitability levels depending on the polarity of the stimulation. One application of non-invasive brain-stimulation has been to modulate a possible inter-hemispheric disinhibition after a stroke. This disinhibition model has been developed mainly for the upper extremity motor system, but it is not known whether the language/speech-motor system shows a similar inter-hemispheric interaction. We aimed to examine physiological evidence of inter- and intra-hemispheric connectivity changes induced by tDCS of the right inferior frontal gyrus (IFG) using arterial-spin labeling (ASL) MRI. Using an MR-compatible DC-Stimulator, we applied anodal stimulation to the right IFG region of nine healthy adults while undergoing non-invasive cerebral blood flow imaging with arterial-spin labeling (ASL) before, during, and after the stimulation. All ASL images were then normalized and timecourses were extracted in regions of interest (ROIs), which were the left and right IFG regions, and the right supramarginal gyrus (SMG) in the inferior parietal lobule. Two additional ROIs (the right occipital lobe and the left fronto-orbital region) were taken as control regions. Using regional correlation coefficients as a surrogate marker of connectivity, we could show that inter-hemispheric connectivity (right IFG with left IFG) decreased significantly (p < 0.05; r-scores from 0.67 to 0.53) between baseline and post-stimulation, while the intra-hemispheric connectivity (right IFG with right SMG) increased significantly (p < 0.05;r-scores from 0.74 to 0.81). A 2 × 2 ANOVA found a significant main effect of HEMISPHERE (F(8) = 6.83, p < 0.01) and a significant HEMISPHERE-by-TIME interaction (F(8) = 4.24, p < 0.05) in connectivity changes. The correlation scores did not change significantly in the control region pairs (right IFG with right occipital and right IFG with left fronto-orbital) over

Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters

DEFF Research Database (Denmark)

Henze, Andrea; Frey, Simone K; Raila, Jens

2010-01-01

) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation...... analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic...

Subcortical structures in humans can be facilitated by transcranial direct current stimulation

NARCIS (Netherlands)

Nonnekes, Johan Hendrik; Arrogi, Anass; Munneke, Moniek; van Asseldonk, Edwin H.F.; Oude Nijhuis, Lars; Geurts, Alexander; Weerdesteyn, Vivian

2014-01-01

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability via application of a weak direct current. Interestingly, it was demonstrated in cats that tDCS can facilitate subcortical structures as well (Bolzonii et al., J

Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

DEFF Research Database (Denmark)

Schulz, Anna M; Stutte, Susanne; Hogl, Sebastian

2015-01-01

Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 defici...

Iron-Deficiency Anemia

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Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

Using tDCS to Explore the Role of the Right Temporo-Parietal Junction in Theory of Mind and Cognitive Empathy.

Science.gov (United States)

Mai, Xiaoqin; Zhang, Wenli; Hu, Xinmu; Zhen, Zhen; Xu, Zhenhua; Zhang, Jing; Liu, Chao

2016-01-01

The right temporo-parietal junction (rTPJ) is thought to be closely related to theory of mind (ToM) and cognitive empathy. In the present study, we investigated whether these socio-cognitive abilities could be modulated with non-invasive transcranial direct current stimulation (tDCS) of the rTPJ. Participants received anodal (excitatory), cathodal (inhibitory), or sham stimulation before performing a social cognitive task which included inferring other's intention (the ToM condition) and inferring other's emotion (the cognitive empathy condition). Our results showed that the accuracy of both ToM and cognitive empathy decreased after receiving the cathodal stimulation, suggesting that altering the cortical excitability in the rTPJ could influence human's socio-cognitive abilities. The results of this study emphasize the critical role of the rTPJ in ToM and cognitive empathy and demonstrate that these socio-cognitive abilities could be modulated by the tDCS.

Design of a DCS Based Model for Continuous Leakage Monitoring System of Rotary Air Preheater of a Thermal Power Plant

Directory of Open Access Journals (Sweden)

Madan BHOWMICK

2011-01-01

Full Text Available The leakage in rotary air preheater makes a considerable contribution to the reduced overall efficiency of fossil-fuel-fired thermal power plants and increase the effect on environment. Since it is normal phenomenon, continuous monitoring of leakage is generally omitted in most power plants. But for accurate analysis of the operation of the thermal power plant, this leakage monitoring plays a vital role. In the present paper, design of a DCS based model for continuous leakages monitoring of rotary air preheater has been described. In the proposed model, the existing DCS based instrumentation system has been modified and online leakage monitoring system has been developed. This model has been installed in a captive power plant with high capacity boilers and very much satisfactory operation of this system has been observed. The observed online data along with their analysis results are presented in this paper.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

Science.gov (United States)

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

2012-11-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

Transcranial direct current stimulation (tDCS) reveals a dissociation between SNARC and MARC effects: Implication for the polarity correspondence account.

Science.gov (United States)

Di Rosa, Elisa; Bardi, Lara; Umiltà, Carlo; Masina, Fabio; Forgione, Margherita; Mapelli, Daniela

2017-08-01

The concept of stimulus response compatibility (SRC) refers to the existence of a privileged association between a specific stimulus feature and a specific response feature. Two examples of SRC are the Spatial Numerical Association of Response Codes (SNARC) and the Markedness Association of Response Codes (MARC) effects. According to the polarity correspondence principle, these two SRC effects occur because of a match between the most salient dimensions of stimulus and response. Specifically, the SNARC effect would be caused by a match between right-sided responses and large numbers, while a match between right-sided responses and even numbers would give rise to the MARC effect. The aim of the present study was to test the validity of the polarity correspondence principle in explaining these two SRC effects. To this end, we applied transcranial direct current stimulation (tDCS) over left and right posterior parietal cortex (PPC), which is thought to be the neural basis of salience processing, during a parity judgement task. Results showed that cathodal tDCS over the PPC significantly reduced the MARC effect but did not affect the SNARC effect, suggesting a dissociation between the two effects. That is, the MARC would rely on a salience processing mechanism, whereas the SNARC would not. Despite this interpretation is in need of further experimental confirmations (i.e., testing different tasks or using different tDCS montages), our results suggest that the polarity correspondence principle can be a plausible explanation only for the MARC effect but not for the SNARC effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

饮酒情景量表中文版应用于大学生的信度和效度分析%Validity and reliability of Chinese Version of Drinking Context Scale ( DCS-9 )

Institute of Scientific and Technical Information of China (English)

胡立荣; 姜德国; 黄汉津; 林崇光; 叶敏捷; 朱盛; 陈策

2012-01-01

目的 评价饮酒情景量表(Drinking Context Scale,DCS-9)中文译本的信、效度,为评估中国高校学生饮酒问题及潜在的心理社会功能损害提供工具.方法 招募温州地区高校学生500名为研究对象,进行DCS-9评定,由2名精神科主治医师根据ICD-10酒精滥用诊断标准进行诊断性面谈.计算Cronbach’s α系数评价量表内部一致性,计算2次测量相关系数考评重测信度,采用验证性因子分析方法考评结构效度,通过DCS-9与酒精使用障碍筛查量表的相关分析来评价效标效度.以ICD-10酒精滥用诊断为参考,根据受试者工作特征曲线下面积判断DCS-9的区分效度,并划定量表的界值分.结果 DCS-9量表总Cronbach’sα系数为0.85,3个分量表Cronbach'sα系数分别为0.77,0.65,0.73.重测信度相关系数为0.95.验证性因素分析显示,GFI=0.959,NFI=0.890,CFI=0.903,TLI=0.902,x2/df=2.950,P=0.037,REMEA =0.041,结构效度符合测量学标准.各条目对其因子的负荷系数在0.59～0.85之间,校标效度相关系数为0.65( P＜0.05).DCS-9界值分为≥14分时区分酒精滥用灵敏度为78.8％,特异度为81.0％.结论 DCS-9中文译本具有较好的信效度,可推荐使用该量表筛查中国高校学生饮酒情景以及酒精滥用问题.%Objective To evaluate the validity and reliability of the Drinking Context Scale ( DCS-9) among the students in colleges of Wenzhou District. Methods A total of 500 students recruited from universities or colleges of Wenzhou District to par-ticipate in the study, all the students were screened by the DCS-9 and Alcohol Use Disorder Identification Test (AUDIT) and in-terviewed by two psychiatrists according to the criteria of ICD-10. Cronbach's a was applied for examining internal consistency of the scale , the correlation analysis was used to examine the test-retest reliability of the scale. Confirmation Factor analysis was used to examine the construct validity. Correlation analysis

Relativistic model-potential oscillator strengths and transition probabilities for 4fsup(n)6s-4fsup(n)6p transitions in Eu(II), Tb(II), and Ho(II) in J1j coupling

International Nuclear Information System (INIS)

Migdalek, J.

1984-01-01

The lowest 4fsup(n)6s-4fsup(n)6p transitions are studied for the Eu(II) (n=7), Tb(II) (n=9), and Ho(II) (n=11) spectra, where the J 1 J coupling is an acceptable approximation. The relativistic radial integrals, required to evaluate the oscillator strengths and transition probabilities, are calculated with the model-potential method, which includes also core-polarization effects. The similarities observed in oscillator strengths for transitions with given ΔJ but different J values are discussed and explained. The computed oscillator strengths are compared with those obtained with the Coulomb approximation and it is found that the latter are only 11-12% lower. The core polarization influence on oscillator strengths is also investigated and the 19-21% decrease in oscillator strengths due to this effect is predicted. This result may, however, be overestimated because of some deficiencies in our procedure. (author)

The Relationship of Vitamin B12 Deficiency and Red Cell Distribution Width-Platelet Ratio

Directory of Open Access Journals (Sweden)

Nigar Yilmaz

2016-09-01

Full Text Available Objective: We aimed to investigate the relationship between vitamin B12 deficiency and red cell distribution widthplatelet ratio (RPR, and the variations in the parameters on vitamin B12 treatment. Methods: One hundred fifty-four patients with untreated vitamin B12 deficiency (56% men, mean age: 50 ± 12.7 years (untreated group, 86 patients with vitamin B12 deficiency (62% men, mean age: 42 ± 20.7 years on vitamin B12 treatment (treated group, and 92 age- and sex-matched control group (54% men, mean age: 45 ± 15.1 years were included in the study. Hematological parameters were evaluated by the method of laser-based flow cytometric impedance, using an automated blood cell counter (ABX Pentra 120 Hematology Blood Analyzer. Results: RPR was significantly reduced in treated group compared with untreated group (4.88 ± 1.06; 6.13 ± 1.27; p0.05. Conclusion: We proposed that vitamin B12 deficiency has effects on RPR and supplementation with vitamin B12 corrects the RPR levels. J Clin Exp Invest 2016; 7 (3: 211-215

Comparison of the rate of uptake and biologic effects of retinol added to human keratinocytes either directly to the culture medium or bound to serum retinol-binding protein

International Nuclear Information System (INIS)

Hodam, J.R.; St Hilaire, P.; Creek, K.E.

1991-01-01

Retinol circulates in the plasma bound to retinol-binding protein (RBP), but the mechanism by which retinol is transferred from RBP to target cells is not known. To study retinol delivery, human keratinocytes (HKc) were incubated with [3H]retinol added directly to the culture medium or bound to RBP and the uptake of [3H]retinol was determined at various times. During the first hour of incubation, the rate of [3H]retinol accumulation by HKc was about 40 times greater when the vitamin was added directly to the media rather than bound to RBP. Although maximal uptake of [3H]retinol added directly to the culture medium occurred at 3 h, the uptake of [3H]retinol from RBP was linear with time for at least 72 h. By 57 h, cell-associated [3H]retinol was the same whether it was added directly to the culture medium or bound to RBP. Excess unlabeled retinol or pretreatment of HKc with retinol had no effect on the uptake of [3H]retinol added directly to the culture medium or bound to RBP. Apo- but not holo-RBP was capable of competing with HKc for the uptake of [3H]retinol from RBP. No specific or saturable binding of 125I-labeled RBP to HKc cultured in the absence or the presence of retinol was found. The dose response of retinol inhibition of cholesterol sulfate synthesis and phorbol ester-induced ornithine decarboxylase activity or retinol modulation of keratin expression was the same whether the retinol was delivered to HKc bound to RBP or added directly to the medium. Our data support a mechanism for retinol delivery from RBP to HKc that does not involve cell-surface RBP receptors but instead suggest that the vitamin is first slowly released from RBP and then becomes cell-associated from the aqueous phase. This mechanism is consistent with the finding that HKc respond identically to retinol whether or not it is delivered to them bound to RBP

Transcranial direct current stimulation (tDCS) Paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: a pilot study.

Science.gov (United States)

Potter-Baker, Kelsey A; Janini, Daniel P; Lin, Yin-Liang; Sankarasubramanian, Vishwanath; Cunningham, David A; Varnerin, Nicole M; Chabra, Patrick; Kilgore, Kevin L; Richmond, Mary Ann; Frost, Frederick S; Plow, Ela B

2017-08-07

Objective Our goal was to determine if pairing transcranial direct current stimulation (tDCS) with rehabilitation for two weeks could augment adaptive plasticity offered by these residual pathways to elicit longer-lasting improvements in motor function in incomplete spinal cord injury (iSCI). Design Longitudinal, randomized, controlled, double-blinded cohort study. Setting Cleveland Clinic Foundation, Cleveland, Ohio, USA. Participants Eight male subjects with chronic incomplete motor tetraplegia. Interventions Massed practice (MP) training with or without tDCS for 2 hrs, 5 times a week. Outcome Measures We assessed neurophysiologic and functional outcomes before, after and three months following intervention. Neurophysiologic measures were collected with transcranial magnetic stimulation (TMS). TMS measures included excitability, representational volume, area and distribution of a weaker and stronger muscle motor map. Functional assessments included a manual muscle test (MMT), upper extremity motor score (UEMS), action research arm test (ARAT) and nine hole peg test (NHPT). Results We observed that subjects receiving training paired with tDCS had more increased strength of weak proximal (15% vs 10%), wrist (22% vs 10%) and hand (39% vs. 16%) muscles immediately and three months after intervention compared to the sham group. Our observed changes in muscle strength were related to decreases in strong muscle map volume (r=0.851), reduced weak muscle excitability (r=0.808), a more focused weak muscle motor map (r=0.675) and movement of weak muscle motor map (r=0.935). Conclusion Overall, our results encourage the establishment of larger clinical trials to confirm the potential benefit of pairing tDCS with training to improve the effectiveness of rehabilitation interventions for individuals with SCI. Trial Registration NCT01539109.

Co-localization of a CD1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in LN-resident DCs for a robust adjuvant effect

Science.gov (United States)

Li, Xiangming; Kawamura, Akira; Andrews, Chasity D.; Miller, Jessica L.; Wu, Douglass; Tsao, Tiffany; Zhang, Min; Oren, Deena; Padte, Neal N.; Porcelli, Steven A.; Wong, Chi-Huey; Kappe, Stefan H. I.; Ho, David D.; Tsuji, Moriya

2015-01-01

A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant natural killer T (iNKT) cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the present study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites (RAS) of a rodent malaria parasite, Plasmodium yoelii, also referred to as irradiated P. yoelii sporozoites (IrPySpz). 7DW8-5 had a superb adjuvant effect only when the glycolipid and IrPySpz were conjointly administered intramuscularly (i.m.). Therefore, we evaluated the impact of distinctly different biodistribution patterns of αGalCer and 7DW8-5 on their respective adjuvant activities. While both glycolipids induce a similar cytokine response in sera of mice injected intravenously, after i.m. injection, αGalCer induces a systemic cytokine response, whereas 7DW8-5 is locally trapped by CD1d expressed by dendritic cells (DCs) in draining lymph nodes (dLNs). Moreover, the i.m. co-administration of 7DW8-5 with IrPySpz results in the recruitment of DCs to dLNs and the activation and maturation of DCs. These events cause the potent adjuvant effect of 7DW8-5, resulting in the enhancement of the CD8+ T-cell response induced by IrPySpz, and, ultimately, improved protection against malaria. Our study is the first to show that the co-localization of a CD1d-binding iNKT-cell stimulatory glycolipid and a vaccine, like RAS, in dLN-resident DCs upon i.m. conjoin administration governs the potency of the adjuvant effect of the glycolipid. PMID:26254338

Good alarm design plays a vital role in successful DCS implementation: Hard learned lessons from petrochemical applications

International Nuclear Information System (INIS)

Wilson, C.; Rothenberg, D.

2006-01-01

Nuclear operators are eager to update their automation infrastructure, but are apprehensive due to the consequences of failure. The process industries have learned that alarm design is critical to a successful Distributed Control System (DCS) implementation. This paper shares valuable insight into how alarms play a key role in successful management of upsets, help focus operator attention, and supply critical information during periods of high stress. (authors)

Live Cell Genomics: RNA Exon-Specific RNA-Binding Protein Isolation.

Science.gov (United States)

Bell, Thomas J; Eberwine, James

2015-01-01

RNA-binding proteins (RBPs) are essential regulatory proteins that control all modes of RNA processing and regulation. New experimental approaches to isolate these indispensable proteins under in vivo conditions are needed to advance the field of RBP biology. Historically, in vitro biochemical approaches to isolate RBP complexes have been useful and productive, but biological relevance of the identified RBP complexes can be imprecise or erroneous. Here we review an inventive experimental to isolate RBPs under the in vivo conditions. The method is called peptide nucleic acid (PNA)-assisted identification of RBP (PAIR) technology and it uses cell-penetrating peptides (CPPs) to deliver photo-activatible RBP-capture molecule to the cytoplasm of the live cells. The PAIR methodology provides two significant advantages over the most commonly used approaches: (1) it overcomes the in vitro limitation of standard biochemical approaches and (2) the PAIR RBP-capture molecule is highly selective and adaptable which allows investigators to isolate exon-specific RBP complexes. Most importantly, the in vivo capture conditions and selectivity of the RBP-capture molecule yield biologically accurate and relevant RBP data.

The LHCb RICH Upgrade: Development of the DCS and DAQ system.

CERN Multimedia

Cavallero, Giovanni

2018-01-01

The LHCb experiment is preparing for an upgrade during the second LHC long shutdown in 2019-2020. In order to fully exploit the LHC flavour physics potential with a five-fold increase in the instantaneous luminosity, a trigger-less readout will be implemented. The RICH detectors will require new photon detectors and a brand new front-end electronics. The status of the integration of the RICH photon detector modules with the MiniDAQ, the prototype of the upgraded LHCb readout architecture, has been reported. The development of the prototype of the RICH Upgrade Experiment Control System, integrating the DCS and DAQ partitions in a single FSM, has been described. The status of the development of the RICH Upgrade Inventory, Bookkeeping and Connectivity database has been reported as well.

Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.

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Laura E Pascal

Full Text Available ELL-associated factor 2 (EAF2 is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/- mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/- mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/- animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors.

Caracterização de sintomas visuais, parâmetros de crescimento e desenvolvimento de Tagetes erecta sob deficiências nutricionais

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Livia Cristina Coelho

2011-06-01

Full Text Available O presente trabalho foi realizado com o objetivo de caracterizar os sintomas de deficiências nutricionais e avaliar o florescimento e parâmetros de crescimento de tagetes africano, em solução nutritiva, sob omissão de macro e micronutrientes. O experimento foi conduzido em casa de vegetação no DCS (UFLA. O delineamento experimental foi inteiramente aleatorizado, com 10 tratamentos representados por: tratamento completo, omissões simples de N, P, K, Ca, Mg, S, B, Cu, Fe e Mn e quatro repetições. À medida que ocorreram as manifestações dos sintomas visuais de deficiências nutricionais, estas foram fotografadas e anotadas. Ao fim da fase experimental foi avaliada a produção de massa seca de parte aérea e raiz, diâmetro do caule e número de inflorescências. A omissão de nutrientes, em solução de cultivo, causa alterações morfológicas traduzidas em sintomas visuais de deficiências. As omissões de N e P são as que mais limitam o crescimento de plantas de tagetes. Plantas de tagetes sob omissões de N, Ca e B não emitem inflorescências. A ordem das omissões que mais limita a produção de matéria seca da parte aérea para plantas de Tagetes erecta é: N>P>K>Fe>Ca>B>Mg>Mn>S.

Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

DEFF Research Database (Denmark)

Guo, L T; Zhang, X U; Kuang, W

2003-01-01

2, lacking domain VI. Interestingly, all mutants lack laminin alpha2 in peripheral nerve. We have demonstrated previously, that overexpression of the human laminin alpha2 in skeletal muscle in dy(2J)/dy(2J) and dy(W)/dy(W) mice under the control of a striated muscle-specific creatine kinase promoter......Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal...

Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function.

Science.gov (United States)

Wang, Yanyan; Huang, Gonghua; Vogel, Peter; Neale, Geoffrey; Reizis, Boris; Chi, Hongbo

2012-02-07

Homeostatic control of dendritic cell (DC) survival is crucial for adaptive immunity, but the molecular mechanism is not well defined. Moreover, how DCs influence immune homeostasis under steady state remains unclear. Combining DC-specific and -inducible deletion systems, we report that transforming growth factor beta-activated kinase 1 (TAK1) is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c(+) cells induced markedly elevated apoptosis, leading to the depletion of DC populations, especially the CD8(+) and CD103(+) DC subsets in lymphoid and nonlymphoid tissues, respectively. TAK1 also contributed to DC development by promoting the generation of DC precursors. Prosurvival signals from Toll-like receptors, CD40 and receptor activator of nuclear factor-κB (RANK) are integrated by TAK1 in DCs, which in turn mediated activation of downstream NF-κB and AKT-Foxo pathways and established a gene-expression program. TAK1 deficiency in DCs caused a myeloid proliferative disorder characterized by expansion of neutrophils and inflammatory monocytes, disrupted T-cell homeostasis, and prevented effective T-cell priming and generation of regulatory T cells. Moreover, TAK1 signaling in DCs was required to prevent myeloid proliferation even in the absence of lymphocytes, indicating a previously unappreciated regulatory mechanism of DC-mediated control of myeloid cell-dependent inflammation. Therefore, TAK1 orchestrates a prosurvival checkpoint in DCs that affects the homeostasis and function of the immune system.

N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: An animal model for human carbonic anhydrase II deficiency syndrome

International Nuclear Information System (INIS)

Lewis, S.E.; Barnett, L.B.; Erickson, R.P.; Venta, P.J.; Tashian, R.E.

1988-01-01

Electrophoretic screening of (C57BL/6J x DBA/2J)F 1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (Ca II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus

Lack of retinoic acid leads to increased langerin-expressing dendritic cells in gut-associated lymphoid tissues.

Science.gov (United States)

Chang, Sun-Young; Cha, Hye-Ran; Chang, Jae-Hoon; Ko, Hyun-Jeong; Yang, Hyungjun; Malissen, Bernard; Iwata, Makoto; Kweon, Mi-Na

2010-04-01

Retinoic acid (RA) is a crucial factor for maintaining homeostasis in the gut, including lymphocyte homing, immunoglobulin (Ig) A production, and T regulatory cells (Treg) and T helper cell 17 (T(H)17) generation. Until now, most attention has focused on the function of dendritic cells (DCs) to initiate adaptive immunity including T and B lymphocytes through RA. To investigate the effects of RA on DCs of gut-associated lymphoid tissue (GALT), we analyzed the phenotype and function of DC subsets from GALT of vitamin A-deficient (VAD) mice. VAD mice were prepared by feeding them a VAD diet over 12 weeks from gestational days 10-14. Here, we report that tremendous increase of langerin(+) DCs occurred in the mesenteric lymph nodes (MLNs) and gut lamina propria of VAD mice dependent on CCR7 signaling. Langerin(+) DCs have phenotypes more similar to those of bone marrow-derived dermal langerin(+) DCs than epidermal Langerhans cells. Moreover, RA receptor antagonists enhance the differentiation of langerin(+) DCs from mouse and human precursors of bone marrow and peripheral blood. Langerin(+) DCs were highly differentiated but less inflammatory than langerin(-) DCs of MLNs of VAD mice. Moreover, tolerance to orally delivered antigen was completely abrogated by depletion of langerin(+) DCs in the VAD mice. These results suggest that generation of langerin(+) DCs in the GALT is tightly regulated by RA and that the microenvironment of tissues determines the phenotype of DCs. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

A technical guide to tDCS, and related non-invasive brain stimulation tools

Science.gov (United States)

Woods, AJ; Antal, A; Bikson, M; Boggio, PS; Brunoni, AR; Celnik, P; Cohen, LG; Fregni, F; Herrmann, CS; Kappenman, ES; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, PC; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, MA

2015-01-01

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain. PMID:26652115

Research on engineering simulator for function validating of DCS in Nuclear Power Plant

International Nuclear Information System (INIS)

Liu Pengfei; Lin Meng; Hou Dong; Yang Yanhua; Chen Zhi

2009-01-01

An engineering simulator for the function validating of Distributed Control System in Nuclear Power Plant (NPP) was developed in this paper.In the engineering simulator, the thermal-hydraulics was modeled by Relap5, the main control system of the NPP was modeled by Matlab/Simulink, the database was built by MySQL, and the control panel was developed by the Visual Studio. NET.Data acquisition system was used to realize the real-time communication between the simulator and the real Distributed Control System in the NPP. The validating results show that the simulator can meet the requirements of validating the hardware and logic control system of DCS in NPP. (authors)

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study

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Huang Gary

2012-07-01

Full Text Available Abstract Background The published literature regarding the relationships between retinol-binding protein 4 (RBP4 and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT, and coronary artery calcification (CAC. Results The mean age of women was 52.9 (± 2.6 years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5 μg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01, but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05. Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile. However, a squared RBP4 term in regression modeling was non-significant (P = 0.10. Conclusions In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. Trial registration ClinicalTrials.gov number NCT

Evaluation of the effect of laser radiation on fibroblast proliferation in repair of skin wounds of rats with iron deficiency anemia

Science.gov (United States)

DeCastro, Isabele C. V.; Oliveira-Sampaio, Susana C. P.; Monteiro, Juliana S. de C.; Ferreira, Maria de Fátima L.; Cangussu, Maria T.; N. dos Santos, Jean; Pinheiro, Antonio Luiz B.

2011-03-01

The aim of this study was to assess the effect of low- level laser therapy (LLLT) on fibroblast proliferation on wound repair of rats with Iron deficiency anemia since there is no reports on literature about this subject. Iron deficiency anemia was induced on 36 newborn rats then an excisional wound was created on the dorsum of the animals which were divided into four groups: (I) - non-anemic, (II) - Anemic, (III) - non-anemic + LLLT, (IV) Anemic+ LLLT. The animals in each group were sacrificed at 7, 14 and 21 days. Laser irradiation was performed on each group (λ660nm,40Mw,CW) by contact mode with a dose of 2,5J/ cm2 in four points on the area of the wound and total of 10J/cm2 per session. Data were evaluated by analysis of variance (ANOVA) followed by Paired t-test. The results showed LLLT was able to stimulate fibroblastic proliferation in rats with iron deficiency anemia at the 21st day while at control group (III) no statistically significant differences was found.

Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

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Johanna Salvermoser

2018-04-01

Full Text Available Conventional dendritic cells (cDCs are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired.

Microarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats.

Science.gov (United States)

Dakshinamurti, Krishnamurti; Bagchi, Rushita A; Abrenica, Bernard; Czubryt, Michael P

2015-12-01

Biotin is a B vitamin involved in multiple metabolic pathways. In humans, biotin deficiency is relatively rare but can cause dermatitis, alopecia, and perosis. Low biotin levels occur in individuals with type-2 diabetes, and supplementation with biotin plus chromium may improve blood sugar control. The acute effect on pancreatic gene expression of biotin repletion following chronic deficiency is unclear, therefore we induced biotin deficiency in adult male rats by feeding them a 20% raw egg white diet for 6 weeks. Animals were then randomized into 2 groups: one group received a single biotin supplement and returned to normal chow lacking egg white, while the second group remained on the depletion diet. After 1 week, pancreata were removed from biotin-deficient (BD) and biotin-repleted (BR) animals and RNA was isolated for microarray analysis. Biotin depletion altered gene expression in a manner indicative of inflammation, fibrosis, and defective pancreatic function. Conversely, biotin repletion activated numerous repair and anti-inflammatory pathways, reduced fibrotic gene expression, and induced multiple genes involved in pancreatic endocrine and exocrine function. A subset of the results was confirmed by quantitative real-time PCR analysis, as well as by treatment of pancreatic AR42J cells with biotin. The results indicate that biotin repletion, even after lengthy deficiency, results in the rapid induction of repair processes in the pancreas.

Vitamin Deficiency Anemia

Science.gov (United States)

... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

Frontal transcranial direct current stimulation (tDCS) abolishes list-method directed forgetting.

Science.gov (United States)

Silas, Jonathan; Brandt, Karen R

2016-03-11

It is a point of controversy as to whether directed forgetting effects are a result of active inhibition or a change of context initiated by the instruction to forget. In this study we test the causal role of active inhibition in directed forgetting. By applying cathodal transcranial direct current stimulation (tDCS) over the right prefrontal cortex we suppressed cortical activity commonly associated with inhibitory control. Participants who underwent real brain stimulation before completing the directed forgetting paradigm showed no directed forgetting effects. Conversely, those who underwent sham brain stimulation demonstrated classical directed forgetting effects. We argue that these findings suggest that inhibition is the primary mechanism that results in directed forgetting costs and benefits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Extreme heterogeneity of polyadenylation sites in mRNAs encoding chloroplast RNA-binding proteins in Nicotiana plumbaginifolia.

Science.gov (United States)

Klahre, U; Hemmings-Mieszczak, M; Filipowicz, W

1995-06-01

We have previously characterized nuclear cDNA clones encoding two RNA binding proteins, CP-RBP30 and CP-RBP-31, which are targeted to chloroplasts in Nicotiana plumbaginifolia. In this report we describe the analysis of the 3'-untranslated regions (3'-UTRs) in 22 CP-RBP30 and 8 CP-RBP31 clones which reveals that mRNAs encoding both proteins have a very complex polyadenylation pattern. Fourteen distinct poly(A) sites were identified among CP-RBP30 clones and four sites among the CP-RBP31 clones. The authenticity of the sites was confirmed by RNase A/T1 mapping of N. plumbaginifolia RNA. CP-RBP30 provides an extreme example of the heterogeneity known to be a feature of mRNA polyadenylation in higher plants. Using PCR we have demonstrated that CP-RBP genes in N. plumbaginifolia and N. sylvestris, in addition to the previously described introns interrupting the coding region, contain an intron located in the 3' non-coding part of the gene. In the case of the CP-RBP31, we have identified one polyadenylation event occurring in this intron.

Omigapil treatment decreases fibrosis and improves respiratory rate in dy(2J mouse model of congenital muscular dystrophy.

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Qing Yu

Full Text Available Congenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients.dy(2J mice were treated with vehicle, 0.1 mg/kg or 1 mg/kg of omigapil daily via oral gavage over 17.5 weeks. Untreated age matched BL6 mice were used as controls. Functional, behavioral and histological measurements were collected.dy(2J mice treated with omigapil showed improved respiratory rates compared to vehicle treated dy(2J mice (396 to 402 vs. 371 breaths per minute, p<0.03 and similar to control mice. There were no statistical differences in normalized forelimb grip strength between dy(2J and controls at baseline or after 17.5 weeks and no significant differences seen among the dy(2J treatment groups. At 30-33 weeks of age, dy(2J mice treated with 0.1 mg/kg omigapil showed significantly more movement time and less rest time compared to vehicle treated. dy(2J mice showed normal cardiac systolic function throughout the trial. dy(2J mice had significantly lower hindlimb maximal (p<0.001 and specific force (p<0.002 compared to the control group at the end of the trial. There were no statistically significant differences in maximal or specific force among treatments. dy(2J mice treated with 0.1 mg/kg/day omigapil showed decreased percent fibrosis in both gastrocnemius (p<0.03 and diaphragm (p<0.001 compared to vehicle, and in diaphragm (p<0.013 when compared to 1 mg/kg/day omigapil treated mice. Omigapil treated dy(2J mice demonstrated decreased apoptosis.Omigapil therapy (0.1 mg/kg improved respiratory rate and decreased skeletal and respiratory muscle fibrosis in dy(2J mice. These results support a putative role for the use of omigapil in laminin deficient congenital muscular dystrophy

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-α and the Gut Microbiota

DEFF Research Database (Denmark)

Hägerbrand, Karin; Westlund, Jessica; Yrlid, Ulf

2015-01-01

Intestinal homeostasis and induction of systemic tolerance to fed Ags (i.e., oral tolerance) rely on the steady-state migration of smallintestinal lamina propria dendritic cells (DCs) into draining mesenteric lymph nodes (MLN). The majority of these migratory DCs express the α integrin chain CD103......, and in this study we demonstrate that the steady-state mobilization of CD103+ DCs into the MLN is in part governed by the IL-1R family/TLR signaling adaptor molecule MyD88. Similar to mice with complete MyD88 deficiency, specific deletion of MyD88 in DCs resulted in a 50–60% reduction in short-term accumulation......, the proportion and phenotypic composition of DCs were similar in mesentericlymph from germ-free and conventionally housed mice. Although TNF-α was required for CD103+ DC migration to the MLN after oral administration of the TLR7 agonist R848, it was not required for the steady-state migration of these cells...

What Are Rare Clotting Factor Deficiencies?

Science.gov (United States)

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Characteristics of retinol accumulation from serum retinol-binding protein by cultured sertoli cells

International Nuclear Information System (INIS)

Shingleton, J.L.; Skinner, M.K.; Ong, D.E.

1989-01-01

The uptake of retinol was examined in cultured Sertoli cells when retinol was provided as a complex with the transport protein retinol-binding protein (RBP). Sertoil cells accumulated [ 3 H]retinol in a time- and temperature-dependent manner. The change in rate of retinol accumulation occurred when the cells had accumulated approximately 0.53 pmol of retinol/μg of cellular DNA. Extraction and HPLC analysis of the cell-associated radioactivity yielded retinol and retinyl esters, indicating that a significant proportion of the accumulated retinol was esterified. Excess unlabeled retinol-RBP competed with [ 3 H]retinol-RBP for [ 3 H]retinol delivery to the cells, indicating that RBP delivery of retinol was a saturable and competable process. However, free [ 3 H]retinol associated with Sertoli cells in a noncompetable manner. The transport constant for specific retinol accumulation from RBP was 3.0 μM. Neither iodinated nor reductively methylated RBP was accumulated by or tightly bound to Sertoli cells. Competition studies indicated, however, that protein recognition is important in the retinol uptake process. RBP, CRBP, and CRBP(II) competed with [ 3 H]retinol-RBP for [ 3 H]retinol accumulation, but free retinol, retinol-bovine serum albumin, and retinol-β-lactoglobulin did not. These studies indicated that Sertoli cell uptake of retinol involved recognition of the retinol-RBP complex at the cell surface with subsequent internalization of retinol, but not RBP

Resource Allocation in a Frequency Hopping PCS1900/GSM/DCS1800 Type of Network

DEFF Research Database (Denmark)

Nielsen, Thomas Toftegaard; Wigard, Jeroen; Michaelsen, Per-Henrik

1999-01-01

Resource allocation in a frequency hopping network is even more problematic than in a traditional network. The combined effect from all serving frequencies has to be considered directly in the allocation process. An algorithm doing this for a PCS1900/GSM/DCS1800 type of network is presented. The ....... A graphical visualisation tool has been developed as well. This tool uses a network quality measure tightly linked to the FER rather than the traditional C/I or BER. Using these statistics an increase in network quality is shown...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

Effect of transcranial direct current stimulation (tDCS over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial

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Pedro Shiozawa

Full Text Available Abstract Introduction: We report a transcranial direct current stimulation (tDCS protocol over the dorsolateral prefrontal cortex (DLPFC combined with cognitive training in schizophrenia. Method: We assessed psychotic symptoms in nine patients using the Positive and Negative Syndrome Scale (PANSS. All evaluations were scored at baseline, at the end of the intervention protocol, and during a 4-week follow-up. The tDCS protocol consisted of 10 consecutive sessions over 5-day periods. We placed the cathode over the right and the anode over the left DLPFC. For sham stimulation, we turned the device off after 60 seconds. Cognitive training consisted of the administration of N-back and sequence learning tasks. Results: We performed an analysis of covariance (ANCOVA to adjust for the dependent variable PANSS, considering the interaction with baseline severity scores (p = 0.619. Mixed analysis of variance (ANOVA showed no statistical significance between the groups regarding final PANSS scores. Conclusion: The results failed to demonstrate that the concomitant use of tDCS and cognitive training is effective to improve clinical outcomes in patients with schizophrenia. The present findings should be analyzed with care, considering the small sample size. Larger controlled trials on electric/cognitive stimulation should be produced in order to enhance therapeutic strategies in schizophrenia.

tDCS Over DLPFC Leads to Less Utilitarian Response in Moral-Personal Judgment.

Science.gov (United States)

Zheng, Haoli; Lu, Xinbo; Huang, Daqiang

2018-01-01

The profound nature of moral judgment has been discussed and debated for centuries. When facing the trade-off between pursuing moral rights and seeking better consequences, most people make different moral choices between two kinds of dilemmas. Such differences were explained by the dual-process theory involving an automatic emotional response and a controlled application of utilitarian decision-rules. In neurocognitive studies, the bilateral dorsolateral prefrontal cortex (DLPFC) has been demonstrated to play an important role in cognitive "rational" control processes in moral dilemmas. However, the profile of results across studies is not entirely consistent. Although one transcranial magnetic stimulation (TMS) study revealed that disrupting the right DLPFC led to less utilitarian responses, other TMS studies indicated that inhibition of the right DLPFC led to more utilitarian choices. Moreover, the right temporoparietal junction (TPJ) is essential for its function of integrating belief and intention in moral judgment, which is related to the emotional process according to the dual-process theory. Relatively few studies have reported the causal relationship between TPJ and participants' moral responses, especially in moral dilemmas. In the present study, we aimed to demonstrate a direct link between the neural and behavioral results by application of transcranial direct current stimulation (tDCS) in the bilateral DLPFC or TPJ of our participants. We observed that activating the right DLPFC as well as inhibiting the left DLPFC led to less utilitarian judgments, especially in moral-personal conditions, indicating that the right DLPFC plays an essential role, not only through its function of moral reasoning but also through its information integrating process in moral judgments. It was also revealed that altering the excitability of the bilateral TPJ using tDCS negligibly altered the moral response in non-moral, moral-impersonal and moral-personal dilemmas

tDCS Over DLPFC Leads to Less Utilitarian Response in Moral-Personal Judgment

Directory of Open Access Journals (Sweden)

Haoli Zheng

2018-03-01

Full Text Available The profound nature of moral judgment has been discussed and debated for centuries. When facing the trade-off between pursuing moral rights and seeking better consequences, most people make different moral choices between two kinds of dilemmas. Such differences were explained by the dual-process theory involving an automatic emotional response and a controlled application of utilitarian decision-rules. In neurocognitive studies, the bilateral dorsolateral prefrontal cortex (DLPFC has been demonstrated to play an important role in cognitive “rational” control processes in moral dilemmas. However, the profile of results across studies is not entirely consistent. Although one transcranial magnetic stimulation (TMS study revealed that disrupting the right DLPFC led to less utilitarian responses, other TMS studies indicated that inhibition of the right DLPFC led to more utilitarian choices. Moreover, the right temporoparietal junction (TPJ is essential for its function of integrating belief and intention in moral judgment, which is related to the emotional process according to the dual-process theory. Relatively few studies have reported the causal relationship between TPJ and participants' moral responses, especially in moral dilemmas. In the present study, we aimed to demonstrate a direct link between the neural and behavioral results by application of transcranial direct current stimulation (tDCS in the bilateral DLPFC or TPJ of our participants. We observed that activating the right DLPFC as well as inhibiting the left DLPFC led to less utilitarian judgments, especially in moral-personal conditions, indicating that the right DLPFC plays an essential role, not only through its function of moral reasoning but also through its information integrating process in moral judgments. It was also revealed that altering the excitability of the bilateral TPJ using tDCS negligibly altered the moral response in non-moral, moral-impersonal and moral

The Evaluation and Application Plan Report for the Development of Nuclear Power Plant DCS Using CASE Tools

Energy Technology Data Exchange (ETDEWEB)

Lee, B.Y.; Moon, H.J.; Yoon, M.H.; Lee, Y.K. [Korea Electric Power Research Institute, Taejon (Korea)

2000-06-01

This report contains the evaluation and application plan report for the development of nuclear power plant DCS using CASE tools. In this report, the necessity of using CASE tools is considered and a available CASE environment is suggested. And, also according to the IEEE Std 1209 Recommended Practice for Evaluation and Selection of CASE Tools, their functional and economical evaluation about available commercial CASE tools is performed and described. (author). 6 figs., 3 tabs.

Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity

International Nuclear Information System (INIS)

Kwasnicka-Crawford, Dorota A.; Vincent, Steven R.

2005-01-01

Microsomal cytochrome P450 reductase catalyzes the one-electron transfer from NADPH via FAD and FMN to various electron acceptors, such as cytochrome P450s or to some anti-cancer quinone drugs. This results in generation of free radicals and toxic oxygen metabolites, which can contribute to the cytotoxicity of these compounds. Recently, a cytosolic NADPH-dependent flavin reductase, NR1, has been described which is highly homologous to the microsomal cytochrome P450 reductase. In this study, we show that over-expression of NR1 in human embryonic kidney cells enhances the cytotoxic action of the model quinone, menadione. Furthermore, we show that a novel human histidine triad protein DCS-1, which is expressed together with NR1 in many tissues, can significantly reduce menadione-induced cytotoxicity in these cells. We also show that DCS-1 binds NF1 and directly modulates its activity. These results suggest that NR1 may play a role in carcinogenicity and cell death associated with one-electron reductions

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

Anti-thrombin III, Protein C, and Protein S deficiency in acute coronary syndrome

Directory of Open Access Journals (Sweden)

Dasnan Ismail

2002-06-01

ACS than low levels of AT III. Protein S deficiency was a reinforcing factor on AT-III deficient to development of ACS. The cut-off point of AT-III without protein S deficiency expected to give single vessel disease was 45%, and 9,5% for the development of triple vessel disease. (Med J Indones 2002; 11: 87-92Keywords: acute coronary syndrome, Anti-thrombin III, Protein C, Protein S

Health Deficiencies

Data.gov (United States)

U.S. Department of Health & Human Services — A list of all health deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

Energy Technology Data Exchange (ETDEWEB)

Wang, Q. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China); Wang, L.X. [Department of Pharmacology, School of Medicine, Shandong University, Jinan (China); Zeng, J.P. [Department of Biochemistry, School of Medicine, Shandong University, Jinan (China); Liu, X.J.; Liang, X.M.; Zhou, Y.B. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China)

2013-09-06

Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.

Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

International Nuclear Information System (INIS)

Wang, Q.; Wang, L.X.; Zeng, J.P.; Liu, X.J.; Liang, X.M.; Zhou, Y.B.

2013-01-01

Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

The Effects of Compensatory Auditory Stimulation and High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Tinnitus Perception - A Randomized Pilot Study.

Science.gov (United States)

Henin, Simon; Fein, Dovid; Smouha, Eric; Parra, Lucas C

2016-01-01

Tinnitus correlates with elevated hearing thresholds and reduced cochlear compression. We hypothesized that reduced peripheral input leads to elevated neuronal gain resulting in the perception of a phantom sound. The purpose of this pilot study was to test whether compensating for this peripheral deficit could reduce the tinnitus percept acutely using customized auditory stimulation. To further enhance the effects of auditory stimulation, this intervention was paired with high-definition transcranial direct current stimulation (HD-tDCS). A randomized sham-controlled, single blind study was conducted in a clinical setting on adult participants with chronic tinnitus (n = 14). Compensatory auditory stimulation (CAS) and HD-tDCS were administered either individually or in combination in order to access the effects of both interventions on tinnitus perception. CAS consisted of sound exposure typical to daily living (20-minute sound-track of a TV show), which was adapted with compressive gain to compensate for deficits in each subject's individual audiograms. Minimum masking levels and the visual analog scale were used to assess the strength of the tinnitus percept immediately before and after the treatment intervention. CAS reduced minimum masking levels, and visual analog scale trended towards improvement. Effects of HD-tDCS could not be resolved with the current sample size. The results of this pilot study suggest that providing tailored auditory stimulation with frequency-specific gain and compression may alleviate tinnitus in a clinical population. Further experimentation with longer interventions is warranted in order to optimize effect sizes.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer ... and symptoms as well as complications from iron-deficiency anemia. Research for Your Health The NHLBI is part of the U.S. Department ...

Spanish Navy Up to Date Data in DCS

Science.gov (United States)