Association of peripheral blood dendritic cells with recurrent pregnancy loss: a case-controlled study.

PubMed

Huang, Chunyu; Zhang, Hongzhan; Chen, Xian; Diao, Lianghui; Lian, Ruochun; Zhang, Xu; Hu, Lina; Zeng, Yong

2016-10-01

Dendritic cells (DCs) have been reported to play an important role in pregnancy. However, the role of DCs in recurrent pregnancy loss (RPL) has not been investigated well. Forty-three women affected by RPL and 16 fertile controls were recruited from June 2013 to December 2014. The peripheral blood DCs subsets, including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), the levels (%) of CD80(+) , CD86(+) , and CD200(+) DCs were analyzed using flow cytometry. The levels of total DCs, mDCs, and CD86(+) DCs were significantly higher (all P<.05); however, the level of CD200(+) DCs in the RPL group was significantly lower than that of the control group (P<.05). The logistical regression analyses showed that the elevated level of mDCs was significantly associated with RPL after adjustment for age (OR: 1.14, 95% CI, 1.01-1.29, P<.05). The elevated level of mDCs was significantly associated with RPL, which might lead to the intervention of targeted immunosuppression in women with RPL. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement.

PubMed

Schuh, Elisabeth; Musumeci, Andrea; Thaler, Franziska S; Laurent, Sarah; Ellwart, Joachim W; Hohlfeld, Reinhard; Krug, Anne; Meinl, Edgar

2017-04-15

The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface. After engagement of TLR7/8 or TLR9, BCMA was detected also on the cell surface of pDCs. The display of BCMA on the surface of human pDCs was accompanied by release of soluble BCMA (sBCMA); inhibition of γ-secretase enhanced surface expression of BCMA and reduced the release of sBCMA by pDCs. In contrast with human pDCs, murine pDCs did not express BCMA, not even after TLR9 activation. In this study, we extend the spectrum of BCMA expression to human pDCs. sBCMA derived from pDCs might determine local availability of its high-affinity ligand APRIL, because sBCMA has been shown to function as an APRIL-specific decoy. Further, therapeutic trials targeting BCMA in patients with multiple myeloma should consider possible effects on pDCs. Copyright © 2017 by The American Association of Immunologists, Inc.

Light Water Reactor Sustainability Program A Reference Plan for Control Room Modernization: Planning and Analysis Phase

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

Jacques Hugo; Ronald Boring; Lew Hanes

2013-09-01

The U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) program is collaborating with a U.S. nuclear utility to bring about a systematic fleet-wide control room modernization. To facilitate this upgrade, a new distributed control system (DCS) is being introduced into the control rooms of these plants. The DCS will upgrade the legacy plant process computer and emergency response facility information system. In addition, the DCS will replace an existing analog turbine control system with a display-based system. With technology upgrades comes the opportunity to improve the overall human-system interaction between the operators and the control room. To optimize operatormore » performance, the LWRS Control Room Modernization research team followed a human-centered approach published by the U.S. Nuclear Regulatory Commission. NUREG-0711, Rev. 3, Human Factors Engineering Program Review Model (O’Hara et al., 2012), prescribes four phases for human factors engineering. This report provides examples of the first phase, Planning and Analysis. The three elements of Planning and Analysis in NUREG-0711 that are most crucial to initiating control room upgrades are: • Operating Experience Review: Identifies opportunities for improvement in the existing system and provides lessons learned from implemented systems. • Function Analysis and Allocation: Identifies which functions at the plant may be optimally handled by the DCS vs. the operators. • Task Analysis: Identifies how tasks might be optimized for the operators. Each of these elements is covered in a separate chapter. Examples are drawn from workshops with reactor operators that were conducted at the LWRS Human System Simulation Laboratory HSSL and at the respective plants. The findings in this report represent generalized accounts of more detailed proprietary reports produced for the utility for each plant. The goal of this LWRS report is to disseminate the technique and provide examples sufficient to serve as a template for other utilities’ projects for control room modernization.« less

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

PubMed

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.

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

PubMed

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.

Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells.

PubMed

Hong, Bangxing; Song, Xiao-Tong; Rollins, Lisa; Berry, Lindsey; Huang, Xue F; Chen, Si-Yi

2011-02-01

Both mucosal and systemic immune responses are required for preventing or containing HIV transmission and chronic infection. However, currently described vaccination approaches are largely ineffective in inducing both mucosal and systemic responses. In this study, we found that the ubiquitin-editing enzyme A20--an inducible feedback inhibitor of the TNFR, RIG-I, and TLR signaling pathways that broadly controls the maturation, cytokine production, and immunostimulatory potency of DCs--restricted systemically immunized DCs to induce both robust mucosal and systemic HIV-specific cellular and humoral responses. Mechanistic studies revealed that A20 regulated DC production of retinoic acid and proinflammatory cytokines, inhibiting the expression of gut-homing receptors on T and B cells. Furthermore, A20-silenced, hyperactivated DCs exhibited an enhanced homing capacity to draining and gut-associated lymphoid tissues (GALTs) after systemic administration. Thus, this study provides insights into the role of A20 in innate immunity. This work may allow the development of an efficient HIV vaccination strategy that is capable of inducing both robust systemic and mucosal anti-HIV cellular and humoral responses.

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

PubMed

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.

Evaluating maturation and genetic modification of human dendritic cells in a new polyolefin cell culture bag system.

PubMed

Macke, Lars; Garritsen, Henk S P; Meyring, Wilhelm; Hannig, Horst; Pägelow, Ute; Wörmann, Bernhard; Piechaczek, Christoph; Geffers, Robert; Rohde, Manfred; Lindenmaier, Werner; Dittmar, Kurt E J

2010-04-01

Dendritic cells (DCs) are applied worldwide in several clinical studies of immune therapy of malignancies, autoimmune diseases, and transplantations. Most legislative bodies are demanding high standards for cultivation and transduction of cells. Closed-cell cultivating systems like cell culture bags would simplify and greatly improve the ability to reach these cultivation standards. We investigated if a new polyolefin cell culture bag enables maturation and adenoviral modification of human DCs in a closed system and compare the results with standard polystyrene flasks. Mononuclear cells were isolated from HLA-A*0201-positive blood donors by leukapheresis. A commercially available separation system (CliniMACS, Miltenyi Biotec) was used to isolate monocytes by positive selection using CD14-specific immunomagnetic beads. The essentially homogenous starting cell population was cultivated in the presence of granulocyte-macrophage-colony-stimulating factor and interleukin-4 in a closed-bag system in parallel to the standard flask cultivation system. Genetic modification was performed on Day 4. After induction of maturation on Day 5, mature DCs could be harvested and cryopreserved on Day 7. During the cultivation period comparative quality control was performed using flow cytometry, gene expression profiling, and functional assays. Both flasks and bags generated mature genetically modified DCs in similar yields. Surface membrane markers, expression profiles, and functional testing results were comparable. The use of a closed-bag system facilitated clinical applicability of genetically modified DCs. The polyolefin bag-based culture system yields DCs qualitatively and quantitatively comparable to the standard flask preparation. All steps including cryopreservation can be performed in a closed system facilitating standardized, safe, and reproducible preparation of therapeutic cells.

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

PubMed

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.

The posterior parietal cortex (PPC) mediates anticipatory motor control.

PubMed

Krause, Vanessa; Weber, Juliane; Pollok, Bettina

2014-01-01

Flexible and precisely timed motor control is based on functional interaction within a cortico-subcortical network. The left posterior parietal cortex (PPC) is supposed to be crucial for anticipatory motor control by sensorimotor feedback matching. Intention of the present study was to disentangle the specific relevance of the left PPC for anticipatory motor control using transcranial direct current stimulation (tDCS) since a causal link remains to be established. Anodal vs. cathodal tDCS was applied for 10 min over the left PPC in 16 right-handed subjects in separate sessions. Left primary motor cortex (M1) tDCS served as control condition and was applied in additional 15 subjects. Prior to and immediately after tDCS, subjects performed three tasks demanding temporal motor precision with respect to an auditory stimulus: sensorimotor synchronization as measure of anticipatory motor control, interval reproduction and simple reaction. Left PPC tDCS affected right hand synchronization but not simple reaction times. Motor anticipation was deteriorated by anodal tDCS, while cathodal tDCS yielded the reverse effect. The variability of interval reproduction was increased by anodal left M1 tDCS, whereas it was reduced by cathodal tDCS. No significant effects on simple reaction times were found. The present data support the hypothesis that left PPC is causally involved in right hand anticipatory motor control exceeding pure motor implementation as processed by M1 and possibly indicating subjective timing. Since M1 tDCS particularly affects motor implementation, the observed PPC effects are not likely to be explained by alterations of motor-cortical excitability. Copyright © 2014 Elsevier Inc. All rights reserved.

Bilateral Transcranial Direct Current Stimulation Reshapes Resting-State Brain Networks: A Magnetoencephalography Assessment

PubMed Central

Turco, Cristina; Di Pino, Giovanni; Arcara, Giorgio

2018-01-01

Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders. PMID:29593782

Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study.

PubMed

Craig, Chesney E; Doumas, Michail

2017-01-01

We investigated whether stimulating the cerebellum and primary motor cortex (M1) using transcranial direct current stimulation (tDCS) could affect postural control in young and older adults. tDCS was employed using a double-blind, sham-controlled design, in which young (aged 18-35) and older adults (aged 65+) were assessed over three sessions, one for each stimulatory condition-M1, cerebellar and sham. The effect of tDCS on postural control was assessed using a sway-referencing paradigm, which induced platform rotations in proportion to the participant's body sway, thus assessing sensory reweighting processes. Task difficulty was manipulated so that young adults experienced a support surface that was twice as compliant as that of older adults, in order to minimise baseline age differences in postural sway. Effects of tDCS on postural control were assessed during, immediately after and 30 minutes after tDCS. Additionally, the effect of tDCS on corticospinal excitability was measured by evaluating motor evoked potentials using transcranial magnetic stimulation immediately after and 30 minutes after tDCS. Minimal effects of tDCS on postural control were found in the eyes open condition only, and this was dependent on the measure assessed and age group. For young adults, stimulation had only offline effects, as cerebellar stimulation showed higher mean power frequency (MPF) of sway 30 minutes after stimulation. For older adults, both stimulation conditions delayed the increase in sway amplitude witnessed between blocks one and two until stimulation was no longer active. In conclusion, despite tDCS' growing popularity, we would caution researchers to consider carefully the type of measures assessed and the groups targeted in tDCS studies of postural control.

Preparation of triple-negative breast cancer vaccine through electrofusion with day-3 dendritic cells.

PubMed

Zhang, Peng; Yi, Shuhong; Li, Xi; Liu, Ruilei; Jiang, Hua; Huang, Zenan; Liu, Yu; Wu, Juekun; Huang, Yong

2014-01-01

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) in human immune system. DC-based tumor vaccine has met with some success in specific malignancies, inclusive of breast cancer. In this study, we electrofused MDA-MB-231 breast cancer cell line with day-3 DCs derived from peripheral blood monocytes, and explored the biological characteristics of fusion vaccine and its anti-tumor effects in vitro. Day-3 mature DCs were generated from day-2 immature DCs by adding cocktails composed of TNF-α, IL-1β, IL-6 and PEG2. Day-3 mature DCs were identified and electofused with breast cancer cells to generate fusion vaccine. Phenotype of fusion cells were identified by fluorescence microscope and flow cytometer. The fusion vaccine was evaluated for T cell proliferation, secretion of IL-12 and IFN-γ, and induction of tumor-specific CTL response. Despite differences in morphology, day-3 and day-7 DC expressed similar surface markers. The secretion of IL-12 and IFN-γ in fusion vaccine group was much higher than that in the control group. Compared with control group, DC-tumor fusion vaccine could better stimulate the proliferation of allogeneic T lymphocytes and kill more breast cancer cells (MDA-MB-231) in vitro. Day-3 DCs had the same function as the day-7 DCs, but with a shorter culture period. Our findings suggested that day-3 DCs fused with whole apoptotic breast cancer cells could elicit effective specific antitumor T cell responses in vitro and may be developed into a prospective candidate for adoptivet immunotherapy.

Monitor weather conditions for cloud seeding control. [Colorado River Basin

NASA Technical Reports Server (NTRS)

Kahan, A. M. (Principal Investigator)

1973-01-01

The author has identified the following significant results. The near real-time DCS platform data transfer to the time-share compare is a working reality. Six stations are now being automatically monitored and displayed with a system delay of 3 to 8 hours from time of data transmission to time of data accessibility on the computer. The DCS platform system has proven itself a valuable tool for near real-time monitoring of mountain precipitation. Data from Wolf Creek Pass were an important input in making the decision when to suspend seeding operations to avoid exceeding suspension criteria in that area. The DCS platforms, as deployed in this investigation, have proven themselves to be reliable weather resistant systems for winter mountain environments in the southern Colorado mountains.

The ALICE-HMPID Detector Control System: Its evolution towards an expert and adaptive system

NASA Astrophysics Data System (ADS)

De Cataldo, G.; Franco, A.; Pastore, C.; Sgura, I.; Volpe, G.

2011-05-01

The High Momentum Particle IDentification (HMPID) detector is a proximity focusing Ring Imaging Cherenkov (RICH) for charged hadron identification. The HMPID is based on liquid C 6F 14 as the radiator medium and on a 10 m 2 CsI coated, pad segmented photocathode of MWPCs for UV Cherenkov photon detection. To ensure full remote control, the HMPID is equipped with a detector control system (DCS) responding to industrial standards for robustness and reliability. It has been implemented using PVSS as Slow Control And Data Acquisition (SCADA) environment, Programmable Logic Controller as control devices and Finite State Machines for modular and automatic command execution. In the perspective of reducing human presence at the experiment site, this paper focuses on DCS evolution towards an expert and adaptive control system, providing, respectively, automatic error recovery and stable detector performance. HAL9000, the first prototype of the HMPID expert system, is then presented. Finally an analysis of the possible application of the adaptive features is provided.

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

PubMed

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.

Transcranial Direct Current Stimulation Improves Executive Dysfunctions in ADHD: Implications for Inhibitory Control, Interference Control, Working Memory, and Cognitive Flexibility.

PubMed

Nejati, Vahid; Salehinejad, Mohammad Ali; Nitsche, Michael A; Najian, Asal; Javadi, Amir-Homayoun

2017-09-01

This study examined effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) on major executive functions (EFs), including response inhibition, executive control, working memory (WM), and cognitive flexibility/task switching in ADHD. ADHD children received (a) left anodal/right cathodal DLPFC tDCS and (b) sham stimulation in Experiment 1 and (a) left anodal DLPFC/right cathodal OFC tDCS, (b) left cathodal DLPFC/right anodal OFC tDCS, and (c) sham stimulation in Experiment 2. The current intensity was 1 mA for 15 min with a 72-hr interval between sessions. Participants underwent Go/No-Go task, N-back test, Wisconsin Card Sorting Test (WCST), and Stroop task after each tDCS condition. Anodal left DLPFC tDCS most clearly affected executive control functions (e.g., WM, interference inhibition), while cathodal left DLPFC tDCS improved inhibitory control. Cognitive flexibility/task switching benefited from combined DLPFC-OFC, but not DLPFC stimulation alone. Task-specific stimulation protocols can improve EFs in ADHD.

Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state.

PubMed

Swiecki, M; Miller, H L; Sesti-Costa, R; Cella, M; Gilfillan, S; Colonna, M

2017-07-01

Plasmacytoid dendritic cells (pDCs) detect viruses initiating antiviral type I interferon responses. The microbiota is known to shape immune responses, but whether it influences pDC homeostasis and/or function is poorly understood. By comparing pDCs in germ-free and specific pathogen-free mice, we found that the microbiota supports homeostatic trafficking by eliciting constitutive levels of the chemokine CCL2 that engages CCR2. Mononuclear phagocytes were required for tonic CCL2 levels. CCL2 was particularly important for trafficking of a CCR2 hi subset of pDCs that produced proinflammatory cytokines and was prone to apoptosis. We further demonstrated that CCR2 was also essential for pDC migration during inflammation. Wild-type (WT):Ccr2 -/- mixed bone marrow chimeras revealed that CCR2 promotes pDC migration in a cell-intrinsic manner. Overall, we identify a novel role for the microbiota in shaping immunity, which includes induction of CCL2 levels that control homeostatic trafficking of pDCs.

Enhanced IFN-α production is associated with increased TLR7 retention in the lysosomes of palasmacytoid dendritic cells in systemic lupus erythematosus.

PubMed

Murayama, Goh; Furusawa, Nanako; Chiba, Asako; Yamaji, Ken; Tamura, Naoto; Miyake, Sachiko

2017-10-19

Interferon-α (IFN-α) is increased and plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Plasmacytoid dendritic cells (pDCs) are the main producer of IFN-α, but their IFN-α producing capacity has been shown to be unchanged or reduced when stimulated with a Toll-like receptor 9 (TLR9) agonist in patients with SLE compared to in healthy individuals. In this study, we investigated the IFN-α-producing capacity of lupus pDCs under different stimulation. pDCs from patients with SLE and healthy controls (HC) were stimulated with TLR9 or TLR7 agonist, and their IFN-α producing capacity was examined by intracellular cytokine staining and flow cytometry. The correlation of IFN-α-producing capacity with serum IFN-α levels and disease activity was assessed. The effect of in vitro IFN-α exposure on IFN-α production by pDCs was examined. Localization of TLR7 in cellular compartments in pDCs was investigated. The IFN-α producing capacity of pDCs was reduced after TLR9 stimulation, but increased when stimulated with a TLR7 agonist in SLE compared to in HC. IFN-α production by pDCs upon TLR9 stimulation was reduced and the percentage of IFN-α + pDC was inversely correlated with disease activity and serum IFN-α levels. However, the TLR7 agonist-induced IFN-α producing capacity of lupus pDCs was enhanced and correlated with disease activity and serum IFN-α. Exposure to IFN-α enhanced IFN-α production of TLR7-stimulated pDCs, but reduced that of pDCs activated with a TLR9 agonist. TLR7 localization was increased in late endosome/lysosome compartments in pDCs from SLE patients. These findings indicate that enhanced TLR7 responses of lupus pDCs, owing to TLR7 retention in late endosome/lysosome and exposure to IFN-α, are associated with the pathogenesis of SLE.

Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study

PubMed Central

Doumas, Michail

2017-01-01

We investigated whether stimulating the cerebellum and primary motor cortex (M1) using transcranial direct current stimulation (tDCS) could affect postural control in young and older adults. tDCS was employed using a double-blind, sham-controlled design, in which young (aged 18–35) and older adults (aged 65+) were assessed over three sessions, one for each stimulatory condition–M1, cerebellar and sham. The effect of tDCS on postural control was assessed using a sway-referencing paradigm, which induced platform rotations in proportion to the participant’s body sway, thus assessing sensory reweighting processes. Task difficulty was manipulated so that young adults experienced a support surface that was twice as compliant as that of older adults, in order to minimise baseline age differences in postural sway. Effects of tDCS on postural control were assessed during, immediately after and 30 minutes after tDCS. Additionally, the effect of tDCS on corticospinal excitability was measured by evaluating motor evoked potentials using transcranial magnetic stimulation immediately after and 30 minutes after tDCS. Minimal effects of tDCS on postural control were found in the eyes open condition only, and this was dependent on the measure assessed and age group. For young adults, stimulation had only offline effects, as cerebellar stimulation showed higher mean power frequency (MPF) of sway 30 minutes after stimulation. For older adults, both stimulation conditions delayed the increase in sway amplitude witnessed between blocks one and two until stimulation was no longer active. In conclusion, despite tDCS’ growing popularity, we would caution researchers to consider carefully the type of measures assessed and the groups targeted in tDCS studies of postural control. PMID:28099522

Real time software for a heat recovery steam generator control system

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

Valdes, R.; Delgadillo, M.A.; Chavez, R.

1995-12-31

This paper is addressed to the development and successful implementation of a real time software for the Heat Recovery Steam Generator (HRSG) control system of a Combined Cycle Power Plant. The real time software for the HRSG control system physically resides in a Control and Acquisition System (SAC) which is a component of a distributed control system (DCS). The SAC is a programmable controller. The DCS installed at the Gomez Palacio power plant in Mexico accomplishes the functions of logic, analog and supervisory control. The DCS is based on microprocessors and the architecture consists of workstations operating as a Man-Machinemore » Interface (MMI), linked to SAC controllers by means of a communication system. The HRSG real time software is composed of an operating system, drivers, dedicated computer program and application computer programs. The operating system used for the development of this software was the MultiTasking Operating System (MTOS). The application software developed at IIE for the HRSG control system basically consisted of a set of digital algorithms for the regulation of the main process variables at the HRSG. By using the multitasking feature of MTOS, the algorithms are executed pseudo concurrently. In this way, the applications programs continuously use the resources of the operating system to perform their functions through a uniform service interface. The application software of the HRSG consist of three tasks, each of them has dedicated responsibilities. The drivers were developed for the handling of hardware resources of the SAC controller which in turn allows the signals acquisition and data communication with a MMI. The dedicated programs were developed for hardware diagnostics, task initializations, access to the data base and fault tolerance. The application software and the dedicated software for the HRSG control system was developed using C programming language due to compactness, portability and efficiency.« less

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

PubMed

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.

Human dendritic cell subsets display distinct interactions with the pathogenic mould Aspergillus fumigatus.

PubMed

Lother, Jasmin; Breitschopf, Tanja; Krappmann, Sven; Morton, C Oliver; Bouzani, Maria; Kurzai, Oliver; Gunzer, Matthias; Hasenberg, Mike; Einsele, Hermann; Loeffler, Juergen

2014-11-01

The mould Aspergillus fumigatus is primarily an opportunistic pathogen of immunocompromised patients. Once fungal spores have been inhaled they encounter cells of the innate immune system, which include dendritic cells (DCs). DCs are the key antigen-presenting cells of the immune system and distinct subtypes, which differ in terms of origin, morphology and function. This study has systematically compared the interactions between A. fumigatus and myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and monocyte-derived DCs (moDCs). Analyses were performed by time-lapse video microscopy, scanning electron microscopy, plating assays, flow cytometry, 25-plex ELISA and transwell assays. The three subsets of DCs displayed distinct responses to the fungus with mDCs and moDCs showing the greatest similarities. mDCs and moDCs both produced rough convolutions and occasionally phagocytic cups upon exposure to A. fumigatus whereas pDCs maintained a smooth appearance. Both mDCs and moDCs phagocytosed conidia and germ tubes, while pDCs did not phagocytose any fungi. Analysis of cytokine release and maturation markers revealed specific differences in pro- and anti-inflammatory patterns between the different DC subsets. These distinct characteristics between the DC subsets highlight their differences and suggest specific roles of moDCs, mDCs and pDCs during their interaction with A. fumigatus in vivo. Copyright © 2014 Elsevier GmbH. All rights reserved.

Bantam System Technology Project

NASA Technical Reports Server (NTRS)

Moon, J. M.; Beveridge, J. R.

1998-01-01

This report focuses on determining a best value, low risk, low cost and highly reliable Data and Command System for support of the launch of low cost vehicles which are to carry small payloads into low earth orbit. The ground-based DCS is considered as a component of the overall ground and flight support system which includes the DCS, flight computer, mission planning system and simulator. Interfaces between the DCS and these other component systems are considered. Consideration is also given to the operational aspects of the mission and of the DCS selected. This project involved: defining requirements, defining an efficient operations concept, defining a DCS architecture which satisfies the requirements and concept, conducting a market survey of commercial and government off-the-shelf DCS candidate systems and rating the candidate systems against the requirements/concept. The primary conclusions are that several low cost, off-the-shelf DCS solutions exist and these can be employed to provide for very low cost operations and low recurring maintenance cost. The primary recommendation is that the DCS design/specification should be integrated within the ground and flight support system design as early as possible to ensure ease of interoperability and efficient allocation of automation functions among the component systems.

Anodal Cerebellar Direct Current Stimulation Reduces Facilitation of Propriospinal Neurons in Healthy Humans.

PubMed

Chothia, Muhammed; Doeltgen, Sebastian; Bradnam, Lynley V

2016-01-01

Coordinated muscle synergies in the human upper limb are controlled, in part, by a neural distribution network located in the cervical spinal cord, known as the cervical propriospinal system. Studies in the cat and non-human primate indicate the cerebellum is indirectly connected to this system via output pathways to the brainstem. Therefore, the cerebellum may indirectly modulate excitability of putative propriospinal neurons (PNs) in humans during upper limb coordination tasks. This study aimed to test whether anodal direct current stimulation (DCS) of the cerebellum modulates PNs and upper limb coordination in healthy adults. The hypothesis was that cerebellar anodal DCS would reduce descending facilitation of PNs and improve upper limb coordination. Transcranial magnetic stimulation (TMS), paired with peripheral nerve stimulation, probed activity in facilitatory and inhibitory descending projections to PNs following an established protocol. Coordination was tested using a pursuit rotor task performed by the non-dominant (ipsilateral) hand. Anodal and sham DCS were delivered over the cerebellum ipsilateral to the non-dominant hand in separate experimental sessions. Anodal DCS was applied to a control site lateral to the vertex in a third session. Twelve right-handed healthy adults participated. Pairing TMS with sub-threshold peripheral nerve stimulation facilitated motor evoked potentials at intensities just above threshold in accordance with the protocol. Anodal cerebellar DCS reduced facilitation without influencing inhibition, but the reduction in facilitation was not associated with performance of the pursuit rotor task. The results of this study indicate dissociated indirect control over cervical PNs by the cerebellum in humans. Anodal DCS of the cerebellum reduced excitability in the facilitatory descending pathway with no effect on the inhibitory pathway to cervical PNs. The reduction in PN excitability is likely secondary to modulation of primary motor cortex or brainstem nuclei, and identifies a neuroanatomical pathway for the cerebellum to assist in coordination of upper limb muscle synergies in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined effect of prefrontal transcranial direct current stimulation and a working memory task on heart rate variability

PubMed Central

Boonstra, Tjeerd W.; Loo, Colleen K.; Martin, Donel

2017-01-01

Prefrontal cortex activity has been associated with changes to heart rate variability (HRV) via mediation of the cortico-subcortical pathways that regulate the parasympathetic and sympathetic branches of the autonomic nervous system. Changes in HRV due to altered prefrontal cortex functioning can be predicted using the neurovisceral integration model, which suggests that prefrontal hyperactivity increases parasympathetic tone and decreases contributions from the sympathetic nervous system. Working memory (WM) tasks and transcranial direct current stimulation (tDCS) have been used independently to modulate brain activity demonstrating changes to HRV in agreement with the model. We investigated the combined effects of prefrontal tDCS and a WM task on HRV. Bifrontal tDCS was administered for 15 minutes at 2mA to 20 participants in a sham controlled, single-blind study using parallel groups. A WM task was completed by participants at three time points; pre-, during-, and post-tDCS, with resting state data collected at similar times. Frequency-domain HRV was computed for high frequency (HF; 0.15–0.4Hz) and low frequency (LF; 0.04–0.15Hz) power reflecting parasympathetic and sympathetic branch activity, respectively. Response time on the WM task, but not accuracy, improved from baseline to during-tDCS and post-tDCS with sham, but not active, stimulation. HF-HRV was significantly increased in the active tDCS group compared to sham, lasting beyond cessation of stimulation. Additionally, HF-HRV showed a task-related reduction in power during performance on the WM task. Changes in LF-HRV were moderately inversely correlated (r > 0.4) with changes in WM accuracy during and following tDCS compared to baseline levels. Stimulation of the prefrontal cortex resulted in changes to the parasympathetic branch of the nervous system in agreement with a linearly additive interpretation of effects. Sympathetic activity was not directly altered by tDCS, but was correlated with changes in WM performance. This suggests that the parasympathetic and sympathetic branches respond differentially due to similar, but distinct neural pathways. Given the ease of HRV data collection, studies of prefrontal tDCS would benefit from collection of this data as it provides unique insight into tDCS effects resulting from propagation through brain networks. PMID:28771509

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

PubMed

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.

Effects of transcranial direct current stimulation on the control of finger force during dexterous manipulation in healthy older adults.

PubMed

Parikh, Pranav J; Cole, Kelly J

2015-01-01

The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults.

Effects of anodal tDCS on lumbar propriospinal system in healthy subjects.

PubMed

Roche, N; Lackmy, A; Achache, V; Bussel, B; Katz, R

2012-05-01

It has recently been shown that transcranial direct current stimulation (tDCS) (1) can modify lumbar spinal network excitability and (2) decreases cervical propriospinal system excitability. Thus the purpose of this series of experiments was to determine if anodal tDCS applied over the leg motor cortex area induces changes in lumbar propriospinal system excitability. To that end, the effects of anodal tDCS and sham tDCS on group I and group II propriospinal facilitation of quadriceps motoneurones were studied in healthy subjects. Common peroneal nerve group I and group II quadriceps H-reflex facilitation was assessed in 15 healthy subjects in two randomised conditions: anodal tDCS condition and sham tDCS condition. Recordings were performed before, during and after the end of the cortical stimulation. Compared to sham, anodal tDCS decreases significantly CPN-induced group I and II quadriceps H-reflex facilitation during and also after the end of the cortical stimulation. Anodal tDCS induces (1) modulation of lumbar propriospinal system excitability (2) post-effects on spinal network. These results open a new vista to regulate propriospinal lumbar system excitability in patients and suggest that anodal tDCS would be interesting for neuro-rehabilitation of patients with central nervous system lesions. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. 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.

PubMed

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.

Abnormal costimulatory phenotype and function of dendritic cells before and after the onset of severe murine lupus

PubMed Central

Colonna, Lucrezia; Dinnall, Joudy-Ann; Shivers, Debra K; Frisoni, Lorenza; Caricchio, Roberto; Gallucci, Stefania

2006-01-01

We analyzed the activation and function of dendritic cells (DCs) in the spleens of diseased, lupus-prone NZM2410 and NZB-W/F1 mice and age-matched BALB/c and C57BL/6 control mice. Lupus DCs showed an altered ex vivo costimulatory profile, with a significant increase in the expression of CD40, decreased expression of CD80 and CD54, and normal expression of CD86. DCs from young lupus-prone NZM2410 mice, before the development of the disease, expressed normal levels of CD80 and CD86 but already overexpressed CD40. The increase in CD40-positive cells was specific for DCs and involved the subset of myeloid and CD8α+ DCs before disease onset, with a small involvement of plasmacytoid DCs in diseased mice. In vitro data from bone marrow-derived DCs and splenic myeloid DCs suggest that the overexpression of CD40 is not due to a primary alteration of CD40 regulation in DCs but rather to an extrinsic stimulus. Our analyses suggest that the defect of CD80 in NZM2410 and NZB-W/F1 mice, which closely resembles the costimulatory defect found in DCs from humans with systemic lupus erythematosus, is linked to the autoimmune disease. The increase in CD40 may instead participate in disease pathogenesis, being present months before any sign of autoimmunity, and its downregulation should be explored as an alternative to treatment with anti-CD40 ligand in lupus. PMID:16507174

GNOCIS an update of the generic NO{sub x} control intelligent system

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

Holmes, R.; Mayes, I.; Irons, R.

1996-01-01

GNOCIS is an on-line enhancement to existing power plant Digital Control Systems (DCS) designed to reduce NO{sub x} emissions while meeting other operational constraints, such as heat rate and CO emissions. It can also be used to minimize unburned carbon while meeting a specified NO{sub x} limit, or any combination of emissions/performance variables that can be quantified by a common metric and are affected by DCS - adjustable parameters. The core of the system is an adaptive neural network model of the NO{sub x} generation characteristics of the boiler. The software applies an optimizing procedure to identify the best setpointsmore » for the plant. The recommended setpoints can be either conveyed to the operator via the DCS in an advisory mode, or implemented automatically in a closed-loop mode. GNOCIS is designed to run on a stand-alone workstation connected to the DCS via the data highway. Sensor validation techniques have been incorporated. The goal for GNOSIS is to deliver 10-35% reductions in NO{sub x} from baseline conditions while maintaining or improving other operational constraints. Preliminary results are presented for demonstrations at two power plants: (1) 500-MW T-fired boiler at PowerGen`s Kingsnorth Station, (2) 250-MW Opposed-fired boiler at Alabama Power Company`s Gaston Station.« less

Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis.

PubMed

Kerrin, Aoife; Fitch, Paul; Errington, Claire; Kerr, Dennis; Waxman, Liz; Riding, Kay; McCormack, Jon; Mehendele, Felicity; McSorley, Henry; MacKenzie, Karen; Wronski, Sabine; Braun, Armin; Levin, Richard; Theilen, Ulf; Schwarze, Jürgen

2017-07-01

The pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in infants remains poorly understood. Mouse models implicate pulmonary T cells in the development of RSV disease. T cell responses are initiated by dendritic cells (DCs), which accumulate in lungs of RSV-infected mice. In infants with RSV bronchiolitis, previous reports have shown that DCs are mobilised to the nasal mucosa, but data on lower airway DC responses are lacking. To determine the presence and phenotype of DCs and associated immune cells in bronchoalveolar lavage (BAL) and peripheral blood samples from infants with RSV bronchiolitis. Infants intubated and ventilated due to severe RSV bronchiolitis or for planned surgery (controls with healthy lungs) underwent non-bronchoscopic BAL. Immune cells in BAL and blood samples were characterised by flow cytometry and cytokines measured by Human V-Plex Pro-inflammatory Panel 1 MSD kit. In RSV cases, BAL conventional DCs (cDCs), NK T cells, NK cells and pro-inflammatory cytokines accumulated, plasmacytoid DCs (pDCs) and T cells were present, and blood cDCs increased activation marker expression. When stratifying RSV cases by risk group, preterm and older (≥4 months) infants had fewer BAL pDCs than term born and younger (<4 months) infants, respectively. cDCs accumulate in the lower airways during RSV bronchiolitis, are activated systemically and may, through activation of T cells, NK T cells and NK cells, contribute to RSV-induced inflammation and disease. In addition, the small population of airway pDCs in preterm and older infants may reveal a distinct endotype of RSV bronchiolitis with weak antiviral pDC responses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Evidence for local dendritic cell activation in pulmonary sarcoidosis

PubMed Central

2012-01-01

Background Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation. Methods We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naïve allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c+DCs was assessed in mucosal airway biopsies. Results mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNFα release in co-cultures with naïve allogeneic CD4+ T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86+ DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients. Conclusion Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis. PMID:22513006

Improving Interference Control in ADHD Patients with Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Breitling, Carolin; Zaehle, Tino; Dannhauer, Moritz; Bonath, Björn; Tegelbeckers, Jana; Flechtner, Hans-Henning; Krauel, Kerstin

2016-01-01

The use of transcranial direct current stimulation (tDCS) in patients with attention deficit hyperactivity disorder (ADHD) has been suggested as a promising alternative to psychopharmacological treatment approaches due to its local and network effects on brain activation. In the current study, we investigated the impact of tDCS over the right inferior frontal gyrus (rIFG) on interference control in 21 male adolescents with ADHD and 21 age matched healthy controls aged 13–17 years, who underwent three separate sessions of tDCS (anodal, cathodal, and sham) while completing a Flanker task. Even though anodal stimulation appeared to diminish commission errors in the ADHD group, the overall analysis revealed no significant effect of tDCS. Since participants showed a considerable learning effect from the first to the second session, performance in the first session was separately analyzed. ADHD patients receiving sham stimulation in the first session showed impaired interference control compared to healthy control participants whereas ADHD patients who were exposed to anodal stimulation, showed comparable performance levels (commission errors, reaction time variability) to the control group. These results suggest that anodal tDCS of the right inferior frontal gyrus could improve interference control in patients with ADHD. PMID:27147964

Improving Interference Control in ADHD Patients with Transcranial Direct Current Stimulation (tDCS).

PubMed

Breitling, Carolin; Zaehle, Tino; Dannhauer, Moritz; Bonath, Björn; Tegelbeckers, Jana; Flechtner, Hans-Henning; Krauel, Kerstin

2016-01-01

The use of transcranial direct current stimulation (tDCS) in patients with attention deficit hyperactivity disorder (ADHD) has been suggested as a promising alternative to psychopharmacological treatment approaches due to its local and network effects on brain activation. In the current study, we investigated the impact of tDCS over the right inferior frontal gyrus (rIFG) on interference control in 21 male adolescents with ADHD and 21 age matched healthy controls aged 13-17 years, who underwent three separate sessions of tDCS (anodal, cathodal, and sham) while completing a Flanker task. Even though anodal stimulation appeared to diminish commission errors in the ADHD group, the overall analysis revealed no significant effect of tDCS. Since participants showed a considerable learning effect from the first to the second session, performance in the first session was separately analyzed. ADHD patients receiving sham stimulation in the first session showed impaired interference control compared to healthy control participants whereas ADHD patients who were exposed to anodal stimulation, showed comparable performance levels (commission errors, reaction time variability) to the control group. These results suggest that anodal tDCS of the right inferior frontal gyrus could improve interference control in patients with ADHD.

Managing operational documentation in the ALICE Detector Control System

NASA Astrophysics Data System (ADS)

Lechman, M.; Augustinus, A.; Bond, P.; Chochula, P.; Kurepin, A.; Pinazza, O.; Rosinsky, P.

2012-12-01

ALICE (A Large Ion Collider Experiment) is one of the big LHC (Large Hadron Collider) experiments at CERN in Geneve, Switzerland. The experiment is composed of 18 sub-detectors controlled by an integrated Detector Control System (DCS) that is implemented using the commercial SCADA package PVSSII. The DCS includes over 1200 network devices, over 1,000,000 monitored parameters and numerous custom made software components that are prepared by over 100 developers from all around the world. This complex system is controlled by a single operator via a central user interface. One of his/her main tasks is the recovery of anomalies and errors that may occur during operation. Therefore, clear, complete and easily accessible documentation is essential to guide the shifter through the expert interfaces of different subsystems. This paper describes the idea of the management of the operational documentation in ALICE using a generic repository that is built on a relational database and is integrated with the control system. The experience gained and the conclusions drawn from the project are also presented.

Stability Analysis of Distributed Engine Control Systems Under Communication Packet Drop (Postprint)

DTIC Science & Technology

2008-07-01

use, modify, reproduce, release, perform, display, or disclose the work. 14. ABSTRACT Currently, Full Authority Digital Engine Control ( FADEC ...based on a centralized architecture framework is being widely used for gas turbine engine control. However, current FADEC is not able to meet the...system (DEC). FADEC based on Distributed Control Systems (DCS) offers modularity, improved control systems prognostics and fault tolerance along with

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

NASA Astrophysics Data System (ADS)

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.

The COMT Val/Met polymorphism modulates effects of tDCS on response inhibition.

PubMed

Nieratschker, Vanessa; Kiefer, Christoph; Giel, Katrin; Krüger, Rejko; Plewnia, Christian

2015-01-01

Transcranial direct current stimulation (tDCS) is increasingly discussed as a new option to support the cognitive rehabilitation in neuropsychiatric disorders. However, the therapeutic impact of tDCS is limited by high inter-individual variability. Genetic factors most likely contribute to this variability by modulating the effects of tDCS. We aimed to investigate the influence of the COMT Val(108/158)Met polymorphism on cathodal tDCS effects on executive functioning. Cathodal tDCS was applied to the left dorsolateral prefrontal cortex (dlPFC) during the performance of a parametric Go/No-Go test. We demonstrate an impairing effect of cathodal tDCS to the dlPFC on response inhibition. This effect was only found in individuals homozygous for the Val-allele of the COMT Val(108/158)Met polymorphism. No effects of stimulation on executive functions in Met-allele carriers were detected. Our data indicate that i) cathodal, excitability reducing tDCS, interferes with inhibitory cognitive control, ii) the left dlPFC is critically involved in the neuronal network underlying the control of response inhibition, and iii) the COMT Val(108/158)Met polymorphism modulates the impact of cathodal tDCS on inhibitory control. Together with our previous finding that anodal tDCS selectively impairs set-shifting abilities in COMT Met/Met homozygous individuals, these results indicate that genetic factors modulate effects of tDCS on cognitive performance. Therefore, future tDCS research should account for genetic variability in the design and analysis of neurocognitive as well as therapeutic applications to reduce the variability of results and facilitate individualized neurostimulation approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

242A Distributed Control System Year 2000 Acceptance Test Report

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

TEATS, M.C.

1999-08-31

This report documents acceptance test results for the 242-A Evaporator distributive control system upgrade to D/3 version 9.0-2 for year 2000 compliance. This report documents the test results obtained by acceptance testing as directed by procedure HNF-2695. This verification procedure will document the initial testing and evaluation of the potential 242-A Distributed Control System (DCS) operating difficulties across the year 2000 boundary and the calendar adjustments needed for the leap year. Baseline system performance data will be recorded using current, as-is operating system software. Data will also be collected for operating system software that has been modified to correct yearmore » 2000 problems. This verification procedure is intended to be generic such that it may be performed on any D/3{trademark} (GSE Process Solutions, Inc.) distributed control system that runs with the VMSTM (Digital Equipment Corporation) operating system. This test may be run on simulation or production systems depending upon facility status. On production systems, DCS outages will occur nine times throughout performance of the test. These outages are expected to last about 10 minutes each.« less

Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence

PubMed Central

Cunningham, Cameron R.; Champhekar, Ameya; Tullius, Michael V.; Dillon, Barbara Jane; Zhen, Anjie; de la Fuente, Justin Rafael; Herskovitz, Jonathan; Elsaesser, Heidi; Snell, Laura M.; Wilson, Elizabeth B.; de la Torre, Juan Carlos; Kitchen, Scott G.; Horwitz, Marcus A.; Bensinger, Steven J.; Smale, Stephen T.; Brooks, David G.

2016-01-01

Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections. PMID:26808628

Point-of-care-testing of standing posture with Wii balance board and Microsoft Kinect during transcranial direct current stimulation: a feasibility study.

PubMed

Dutta, Arindam; Chugh, Sanjay; Banerjee, Alakananda; Dutta, Anirban

2014-01-01

Non-invasive brain stimulation (NIBS) is a promising tool for facilitating motor function. NIBS therapy in conjunction with training using postural feedback may facilitate physical rehabilitation following posture disorders (e.g., Pusher Syndrome). The objectives of this study were, 1) to develop a low-cost point-of-care-testing (POCT) system for standing posture, 2) to investigate the effects of anodal tDCS on functional reach tasks using the POCT system. Ten community-dwelling elderly (age >50 years) subjects evaluated the POCT system for standing posture during functional reach tasks where their balance score on Berg Balance Scale was compared with that from Center-of-Mass (CoM) - Center-of-Pressure (CoP) posturography. Then, in a single-blind, sham-controlled study, five healthy right-leg dominant subjects (age: 26.4 ± 5.3 yrs) were evaluated using the POCT system under two conditions - with anodal tDCS of primary motor representations of right tibialis anterior muscle and with sham tDCS. The maximum CoP-CoM lean-angle was found to be well correlated with the BBS score in the elderly subjects The anodal tDCS strongly (p = 0.0000) affected the maximum CoP excursions but not the return reaction time in healthy. It was concluded that the CoM-CoP lean-line could be used for posture feedback and monitoring during tDCS therapy in conjunction with balance training exercises.

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

PubMed Central

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

2016-01-01

ABSTRACT 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. PMID:26986456

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

PubMed

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.

Tolerogenic dendritic cells in autoimmune diseases: crucial players in induction and prevention of autoimmunity.

PubMed

Torres-Aguilar, Honorio; Blank, Miri; Jara, Luis J; Shoenfeld, Yehuda

2010-11-01

The immune system has evolved to coordinate responses against numerous invading pathogens and simultaneously remain silent facing self-antigens and those derived from commensal organisms. But, if both processes are not maintained in strict balance, a potential threat can emerge due to the risk of chronic inflammation and/or autoimmunity development. Therefore, there is a negative immune regulation where tolerogenic dendritic cells (tDCs) participate actively. Under steady-state conditions, tDC are notably involved in the elimination of autoreactive T cells at the thymus, and in the control of T cells specific to self and harmless antigens in the periphery. But in the presence of foreign antigens in an inflammatory milieu, dendritic cells (DCs) mature and induce T cells activation and their migration to B cell areas to assist in antibody production. Additionally, there are other factors such as infections, anti tumoral immune responses, trauma-mediated disruption, etc. that may induce alterations in the balance between tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases (ADs). Therefore, in recent years, DCs have emerged as therapeutic targets to control of ADs. Diverse strategies in vitro and/or in animal models of ADs have explored the tolerogenic functions of DCs and demonstrated their feasibility to prevent or control an autoimmune process, but still leaving a void in their application in clinical assays. The purpose of this paper is to give a general overview of the current literature on the significance of tDCs in tolerance maintenance to self and innocuous antigens, the most relevant alterations involved in the pathophysiology of ADs, the cellular and molecular mechanisms involved in their tolerogenic function and the current strategies used to exploit their tolerogenic potential. Published by Elsevier B.V.

Is Motor Learning Mediated by tDCS Intensity?

PubMed Central

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 (sequence) learning task. Our results showed (1) a significant increase in the slope of the learning curve and (2) a significant improvement in motor performance at retention for 1.5 mA atDCS as compared to sham tDCS. No significant differences were reported between 1 mA atDCS and sham tDCS; and between 1.5 mA atDCS and 1 mA atDCS. PMID:23826272

High Frequency Sampling of TTL Pulses on a Raspberry Pi for Diffuse Correlation Spectroscopy Applications.

PubMed

Tivnan, Matthew; Gurjar, Rajan; Wolf, David E; Vishwanath, Karthik

2015-08-12

Diffuse Correlation Spectroscopy (DCS) is a well-established optical technique that has been used for non-invasive measurement of blood flow in tissues. Instrumentation for DCS includes a correlation device that computes the temporal intensity autocorrelation of a coherent laser source after it has undergone diffuse scattering through a turbid medium. Typically, the signal acquisition and its autocorrelation are performed by a correlation board. These boards have dedicated hardware to acquire and compute intensity autocorrelations of rapidly varying input signal and usually are quite expensive. Here we show that a Raspberry Pi minicomputer can acquire and store a rapidly varying time-signal with high fidelity. We show that this signal collected by a Raspberry Pi device can be processed numerically to yield intensity autocorrelations well suited for DCS applications. DCS measurements made using the Raspberry Pi device were compared to those acquired using a commercial hardware autocorrelation board to investigate the stability, performance, and accuracy of the data acquired in controlled experiments. This paper represents a first step toward lowering the instrumentation cost of a DCS system and may offer the potential to make DCS become more widely used in biomedical applications.

High Frequency Sampling of TTL Pulses on a Raspberry Pi for Diffuse Correlation Spectroscopy Applications

PubMed Central

Tivnan, Matthew; Gurjar, Rajan; Wolf, David E.; Vishwanath, Karthik

2015-01-01

Diffuse Correlation Spectroscopy (DCS) is a well-established optical technique that has been used for non-invasive measurement of blood flow in tissues. Instrumentation for DCS includes a correlation device that computes the temporal intensity autocorrelation of a coherent laser source after it has undergone diffuse scattering through a turbid medium. Typically, the signal acquisition and its autocorrelation are performed by a correlation board. These boards have dedicated hardware to acquire and compute intensity autocorrelations of rapidly varying input signal and usually are quite expensive. Here we show that a Raspberry Pi minicomputer can acquire and store a rapidly varying time-signal with high fidelity. We show that this signal collected by a Raspberry Pi device can be processed numerically to yield intensity autocorrelations well suited for DCS applications. DCS measurements made using the Raspberry Pi device were compared to those acquired using a commercial hardware autocorrelation board to investigate the stability, performance, and accuracy of the data acquired in controlled experiments. This paper represents a first step toward lowering the instrumentation cost of a DCS system and may offer the potential to make DCS become more widely used in biomedical applications. PMID:26274961

Cerebellar transcranial direct current stimulation improves adaptive postural control.

PubMed

Poortvliet, Peter; Hsieh, Billie; Cresswell, Andrew; Au, Jacky; Meinzer, Marcus

2018-01-01

Rehabilitation interventions contribute to recovery of impaired postural control, but it remains a priority to optimize their effectiveness. A promising strategy may involve transcranial direct current stimulation (tDCS) of brain areas involved in fine-tuning of motor adaptation. This study explored the effects of cerebellar tDCS (ctDCS) on postural recovery from disturbance by Achilles tendon vibration. Twenty-eight healthy volunteers participated in this sham-ctDCS controlled study. Standing blindfolded on a force platform, four trials were completed: 60 s quiet standing followed by 20 min active (anodal-tDCS, 1 mA, 20 min, N = 14) or sham-ctDCS (40 s, N = 14) tDCS; three quiet standing trials with 15 s of Achilles tendon vibration and 25 s of postural recovery. Postural steadiness was quantified as displacement, standard deviation and path derived from the center of pressure (COP). Baseline demographics and quiet standing postural steadiness, and backwards displacement during vibration were comparable between groups. However, active-tDCS significantly improved postural steadiness during vibration and reduced forward displacement and variability in COP derivatives during recovery. We demonstrate that ctDCS results in short-term improvement of postural adaptation in healthy individuals. Future studies need to investigate if multisession ctDCS combined with training or rehabilitation interventions can induce prolonged improvement of postural balance. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Transcranial direct current stimulation versus user training on improving online myoelectric control for amputees

NASA Astrophysics Data System (ADS)

Pan, Lizhi; Zhang, Dingguo; Jiang, Ning; Sheng, Xinjun; Zhu, Xiangyang

2017-08-01

Objective. Transcranial direct current stimulation (tDCS) and user training (UT) are two types of methods to improve myoelectric control performance for amputees. In this study, we compared the independent effect between tDCS and UT, and investigated the combined effect of tDCS and UT. Approach. An online paradigm of simultaneous and proportional control (SPC) based on electromyography (EMG) was adopted. The proposed experiments were conducted on six naïve unilateral trans-radial amputees. The subjects each received three types of 20 min interventions: active tDCS with motor training (tDCS  +  UT), active tDCS with quiet sitting (tDCS), and sham tDCS with motor training (UT). The interventions were applied at one week intervals in a randomized order. The subjects performed online control of a feedback arrow with two degrees of freedom (DoFs) to accomplish target reaching motor tasks in pre-sessions and post-sessions. We compared the performance, measured by completion rate, completion time, and efficiency coefficient, between pre-sessions and post-sessions. Main results. The results showed that the intervention tDCS  +  UT and tDCS significantly improved the online SPC performance (i.e. improved the completion rate; reduced the completion time; and improved the efficiency coefficient), while intervention UT did not significantly change the performance. The results also showed that the online SPC performance after intervention tDCS  +  UT and tDCS was not significantly different, but both were significantly better than that after intervention UT. Significance. tDCS could be an effective intervention to improve the online SPC performance in a short time.

Cognitive Training and Transcranial Direct Current Stimulation for Mild Cognitive Impairment in Parkinson's Disease: A Randomized Controlled Trial

PubMed Central

Gasson, Natalie; Johnson, Andrew R.; Booth, Leon; Loftus, Andrea M.

2018-01-01

This study examined whether standard cognitive training, tailored cognitive training, transcranial direct current stimulation (tDCS), standard cognitive training + tDCS, or tailored cognitive training + tDCS improved cognitive function and functional outcomes in participants with PD and mild cognitive impairment (PD-MCI). Forty-two participants with PD-MCI were randomized to one of six groups: (1) standard cognitive training, (2) tailored cognitive training, (3) tDCS, (4) standard cognitive training + tDCS, (5) tailored cognitive training + tDCS, or (6) a control group. Interventions lasted 4 weeks, with cognitive and functional outcomes measured at baseline, post-intervention, and follow-up. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12614001039673). While controlling for moderator variables, Generalized Linear Mixed Models (GLMMs) showed that when compared to the control group, the intervention groups demonstrated variable statistically significant improvements across executive function, attention/working memory, memory, language, activities of daily living (ADL), and quality of life (QOL; Hedge's g range = 0.01 to 1.75). More outcomes improved for the groups that received standard or tailored cognitive training combined with tDCS. Participants with PD-MCI receiving cognitive training (standard or tailored) or tDCS demonstrated significant improvements on cognitive and functional outcomes, and combining these interventions provided greater therapeutic effects. PMID:29780572

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial.

PubMed

Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S; Campbell, Iain C; Schmidt, Ulrike

2017-01-01

Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial

PubMed Central

Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S.; Campbell, Iain C.; Schmidt, Ulrike

2017-01-01

Background Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. Objective This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Methods Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. Results AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. Conclusions These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN. PMID:28121991

Effects of a dynamic core stability program on the biomechanics of cutting maneuvers: A randomized controlled trial.

PubMed

Whyte, E F; Richter, C; O'Connor, S; Moran, K A

2018-02-01

Deficits in trunk control predict ACL injuries which frequently occur during high-risk activities such as cutting. However, no existing trunk control/core stability program has been found to positively affect trunk kinematics during cutting activities. This study investigated the effectiveness of a 6-week dynamic core stability program (DCS) on the biomechanics of anticipated and unanticipated side and crossover cutting maneuvers. Thirty-one male, varsity footballers participated in this randomized controlled trial. Three-dimensional trunk and lower limb biomechanics were captured in a motion analysis laboratory during the weight acceptance phase of anticipated and unanticipated side and crossover cutting maneuvers at baseline and 6-week follow-up. The DCS group performed a DCS program three times weekly for 6 weeks in a university rehabilitation room. Both the DCS and control groups concurrently completed their regular practice and match play. Statistical parametric mapping and repeated measures analysis of variance were used to determine any group (DCS vs control) by time (pre vs post) interactions. The DCS resulted in greater internal hip extensor (P=.017, η 2 =0.079), smaller internal knee valgus (P=.026, η 2 =0.076), and smaller internal knee external rotator moments (P=.041, η 2 =0.066) during anticipated side cutting compared with the control group. It also led to reduced posterior ground reaction forces for all cutting activities (P=.015-.030, η 2 =0.074-0.105). A 6-week DCS program did not affect trunk kinematics, but it did reduce a small number of biomechanical risk factors for ACL injury, predominantly during anticipated side cutting. A DCS program could play a role in multimodal ACL injury prevention programs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells.

PubMed

Marcos-Campos, I; Asín, L; Torres, T E; Marquina, C; Tres, A; Ibarra, M R; Goya, G F

2011-05-20

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The number of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1-5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min and the viability of the blank DCs (i.e. without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH(2)(+)) or negative (COOH(-)) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the number of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.

Enhancement of preoxygenation for decompression sickness protection: effect of exercise duration

NASA Technical Reports Server (NTRS)

Webb, James T.; Pilmanis, Andrew A.; Fischer, Michele D.; Kannan, Nandini

2002-01-01

INTRODUCTION: Since strenuous exercise for 10 min during preoxygenation was shown to provide better protection from decompression sickness (DCS) incidence than resting preoxygenation, a logical question was: would a longer period of strenuous exercise improve protection even further? HYPOTHESIS: Increased strenuous exercise duration during preoxygenation increases DCS protection. METHODS: There were 60 subjects, 30 men and 30 women, who were exposed to 9,144 m (4.3 psia) for 4 h while performing mild, upper body exercise. Before the exposures, each subject performed three preoxygenation profiles on different days in balanced order: a 90-min resting preoxygenation control; a 240-min resting preoxygenation control; and a 90-min preoxygenation including exercise during the first 15 min. The subjects were monitored at altitude for venous gas emboli (VGE) with an echo-imaging system and observed for signs and symptoms of DCS. RESULTS: There were no significant differences in occurrence of DCS following any of the three preoxygenation procedures. Results were also comparable to an earlier report of 42% DCS with a 60-min preoxygenation including a 10-min exercise. There was no difference between VGE incidence in the comparison of protection offered by a 90-min preoxygenation with or without 13 min of strenuous exercise. The DCS incidence following a 240-min resting preoxygenation, 40%, was higher than observed during NASA studies and nearly identical with the earlier 42% DCS after a 60-min preoxygenation including exercise during the first 10 min. CONCLUSION: The protection offered by a 10 min exercise in a 60-min preoxygenation was not increased with extension of the preoxygenation exercise period to 15 min in a 90-min preoxygenation, indicating an upper time limit to the beneficial effects of strenuous exercise.

Electrifying the motor engram: effects of tDCS on motor learning and control

PubMed Central

de Xivry, Jean-Jacques Orban; Shadmehr, Reza

2014-01-01

Learning to control our movements accompanies neuroplasticity of motor areas of the brain. The mechanisms of neuroplasticity are diverse and produce what is referred to as the motor engram, i.e. the neural trace of the motor memory. Transcranial direct current stimulation (tDCS) alters the neural and behavioral correlates of motor learning, but its precise influence on the motor engram is unknown. In this review, we summarize the effects of tDCS on neural activity and suggest a few key principles: 1) firing rates are increased by anodal polarization and decreased by cathodal polarization, 2) anodal polarization strengthens newly formed associations, and 3) polarization modulates the memory of new/preferred firing patterns. With these principles in mind, we review the effects of tDCS on motor control, motor learning, and clinical applications. The increased spontaneous and evoked firing rates may account for the modulation of dexterity in non-learning tasks by tDCS. The facilitation of new association may account for the effect of tDCS on learning in sequence tasks while the ability of tDCS to strengthen memories of new firing patterns may underlie the effect of tDCS on consolidation of skills. We then describe the mechanisms of neuroplasticity of motor cortical areas and how they might be influenced by tDCS. We end with current challenges for the fields of brain stimulation and motor learning. PMID:25200178

Electrifying the motor engram: effects of tDCS on motor learning and control.

PubMed

Orban de Xivry, Jean-Jacques; Shadmehr, Reza

2014-11-01

Learning to control our movements is accompanied by neuroplasticity of motor areas of the brain. The mechanisms of neuroplasticity are diverse and produce what is referred to as the motor engram, i.e., the neural trace of the motor memory. Transcranial direct current stimulation (tDCS) alters the neural and behavioral correlates of motor learning, but its precise influence on the motor engram is unknown. In this review, we summarize the effects of tDCS on neural activity and suggest a few key principles: (1) Firing rates are increased by anodal polarization and decreased by cathodal polarization, (2) anodal polarization strengthens newly formed associations, and (3) polarization modulates the memory of new/preferred firing patterns. With these principles in mind, we review the effects of tDCS on motor control, motor learning, and clinical applications. The increased spontaneous and evoked firing rates may account for the modulation of dexterity in non-learning tasks by tDCS. The facilitation of new association may account for the effect of tDCS on learning in sequence tasks while the ability of tDCS to strengthen memories of new firing patterns may underlie the effect of tDCS on consolidation of skills. We then describe the mechanisms of neuroplasticity of motor cortical areas and how they might be influenced by tDCS. We end with current challenges for the fields of brain stimulation and motor learning.

Effects of Combining a Brief Cognitive Intervention with Transcranial Direct Current Stimulation on Pain Tolerance: A Randomized Controlled Pilot Study.

PubMed

Powers, Abigail; Madan, Alok; Hilbert, Megan; Reeves, Scott T; George, Mark; Nash, Michael R; Borckardt, Jeffrey J

2018-04-01

Cognitive behavioral therapy has been shown to be effective for treating chronic pain, and a growing literature shows the potential analgesic effects of minimally invasive brain stimulation. However, few studies have systematically investigated the potential benefits associated with combining approaches. The goal of this pilot laboratory study was to investigate the combination of a brief cognitive restructuring intervention and transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex in affecting pain tolerance. Randomized, double-blind, placebo-controlled laboratory pilot. Medical University of South Carolina. A total of 79 healthy adult volunteers. Subjects were randomized into one of six groups: 1) anodal tDCS plus a brief cognitive intervention (BCI); 2) anodal tDCS plus pain education; 3) cathodal tDCS plus BCI; 4) cathodal tDCS plus pain education; 5) sham tDCS plus BCI; and 6) sham tDCS plus pain education. Participants underwent thermal pain tolerance testing pre- and postintervention using the Method of Limits. A significant main effect for time (pre-post intervention) was found, as well as for baseline thermal pain tolerance (covariate) in the model. A significant time × group interaction effect was found on thermal pain tolerance. Each of the five groups that received at least one active intervention outperformed the group receiving sham tDCS and pain education only (i.e., control group), with the exception of the anodal tDCS + education-only group. Cathodal tDCS combined with the BCI produced the largest analgesic effect. Combining cathodal tDCS with BCI yielded the largest analgesic effect of all the conditions tested. Future research might find stronger interactive effects of combined tDCS and a cognitive intervention with larger doses of each intervention. Because this controlled laboratory pilot employed an acute pain analogue and the cognitive intervention did not authentically represent cognitive behavioral therapy per se, the implications of the findings on chronic pain management remain unclear.

Surgeon preparedness for mass casualty events: Adapting essential military surgical lessons for the home front.

PubMed

Remick, Kyle N; Shackelford, Stacy; Oh, John S; Seery, Jason M; Grabo, Daniel; Chovanes, John; Gross, Kirby R; Nessen, Shawn C; Tai, Nigel Rm; Rickard, Rory F; Elster, Eric; Schwab, C W

2016-01-01

Military surgeons have gained familiarity and experience with mass casualty events (MCEs) as a matter of routine over the course of the last two conflicts in Afghanistan and Iraq. Over the same period of time, civilian surgeons have increasingly faced complex MCEs on the home front. Our objective is to summarize and adapt these combat surgery lessons to enhance civilian surgeon preparedness for complex MCEs on the home front. The authors describe the unique lessons learned from combat surgery over the course of the wars in Afghanistan and Iraq and adapt these lessons to enhance civilian surgical readiness for a MCE on the home front. Military Damage Control Surgery (mDCS) combines the established concept of clinical DCS (cDCS) with key combat situational awareness factors that enable surgeons to optimally care for multiple, complex patients, from multiple simultaneous events, with limited resources. These additional considerations involve the surgeon's role of care within the deployed trauma system and the battlefield effects. The proposed new concept of mass casualty DCS (mcDCS) similarly combines cDCS decisions with key factors of situational awareness for civilian surgeons faced with complex MCEs to optimize outcomes. The additional considerations for a civilian MCE include the surgeon's role of care within the regional trauma system and the incident effects. Adapting institutionalized lessons from combat surgery to civilian surgical colleagues will enhance national preparedness for complex MCEs on the home front.

Applications of ERTS-1 Data Collection System (DCS) in the Arizona Regional Ecological Test Site (ARETS). [water management, streamflow rates, flood control

NASA Technical Reports Server (NTRS)

Schumann, H. H. (Principal Investigator)

1973-01-01

The author has identified the following significant results. The DCS water-stage data from the USGS streamflow gaging station on the Verde River near Camp Verde furnished information sufficient for the accurate computation of daily mean streamflow rates during the first 2 months of operation. Daily mean flow rates computed from the DCS data agreed with those computed from the digital recorder data within + or - 5% during periods of stable or slowly changing flow and within + or - 10% during periods of rapidly changing high flow. The SRP was furnished near-real time DCS information on snow moisture content and streamflow rates for use in the management and operation of the multiple-use reservoir system. The SRP, by prudent water management and the use of near-real time hydrologic data furnished by microwave and ERTS DCS telemetry, was successful in anticipating the amount of flow into the Salt and Verde Rivers and in the subsequent release of water at rates that did not create flooding in metropolitan Phoenix. Only minor flooding occurred along the Gila River west of Phoenix. According to the Maricopa County Civil Defense agency, wage and salary losses of about $11,400,000 resulted from closing of roads across the Salt River in the winter and spring of 1972-73; however, the number and duration of the closing were minimized by use of DCS data.

Modulating inhibitory control with direct current stimulation of the superior medial frontal cortex.

PubMed

Hsu, Tzu-Yu; Tseng, Lin-Yuan; Yu, Jia-Xin; Kuo, Wen-Jui; Hung, Daisy L; Tzeng, Ovid J L; Walsh, Vincent; Muggleton, Neil G; Juan, Chi-Hung

2011-06-15

The executive control of voluntary action involves not only choosing from a range of possible actions but also the inhibition of responses as circumstances demand. Recent studies have demonstrated that many clinical populations, such as people with attention-deficit hyperactivity disorder, exhibit difficulties in inhibitory control. One prefrontal area that has been particularly associated with inhibitory control is the pre-supplementary motor area (Pre-SMA). Here we applied non-invasive transcranial direct current stimulation (tDCS) over Pre-SMA to test its role in this behavior. tDCS allows for current to be applied in two directions to selectively excite or suppress the neural activity of Pre-SMA. Our results showed that anodal tDCS improved efficiency of inhibitory control. Conversely, cathodal tDCS showed a tendency towards impaired inhibitory control. To our knowledge, this is the first demonstration of non-invasive intervention tDCS altering subjects' inhibitory control. These results further our understanding of the neural bases of inhibitory control and suggest a possible therapeutic intervention method for clinical populations. Copyright © 2011 Elsevier Inc. All rights reserved.

Disease-Associated Plasmacytoid Dendritic Cells

PubMed Central

Li, Shuang; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-01-01

Plasmacytoid dendritic cells (pDCs), also called natural interferon (IFN)-producing cells, represent a specialized cell type within the innate immune system. pDCs are specialized in sensing viral RNA and DNA by toll-like receptor-7 and -9 and have the ability to rapidly produce massive amounts of type 1 IFNs upon viral encounter. After producing type 1 IFNs, pDCs differentiate into professional antigen-presenting cells, which are capable of stimulating T cells of the adaptive immune system. Chronic activation of human pDCs by self-DNA or mitochondrial DNA contributes to the pathogenesis of systemic lupus erythematosis and IFN-related autoimmune diseases. Under steady-state conditions, pDCs play an important role in immune tolerance. In many types of human cancers, recruitment of pDCs to the tumor microenvironment contributes to the induction of immune tolerance. Here, we provide a systemic review of recent progress in studies on the role of pDCs in human diseases, including cancers and autoimmune/inflammatory diseases. PMID:29085361

Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a double-blind, sham-controlled study.

PubMed

Fridriksson, Julius; Richardson, Jessica D; Baker, Julie M; Rorden, Chris

2011-03-01

Previous evidence suggests that anodal transcranial direct current stimulation (A-tDCS) applied to the left hemisphere can improve aphasic participants' ability to name common objects. The current study further examined this issue in a more tightly controlled experiment in participants with fluent aphasia. We examined the effect of A-tDCS on reaction time during overt picture naming in 8 chronic stroke participants. Anode electrode placement targeted perilesional brain regions that showed the greatest activation on a pretreatment functional MRI scan administered during overt picture naming with the reference cathode electrode placed on the contralateral forehead. A-tDCS (1 mA; 20-minute) was compared with sham tDCS (S-tDCS) in a crossover design. Participants received 10 sessions of computerized anomia treatment; 5 sessions included A-tDCS and 5 included S-tDCS. Coupling A-tDCS with behavioral language treatment reduced reaction time during naming of trained items immediately posttreatment (Z=1.96, P=0.025) and at subsequent testing 3 weeks later (Z=2.52, P=0.006). A-tDCS administered during language treatment decreased processing time during picture naming by fluent aphasic participants. Additional studies combining A-tDCS, an inexpensive method with no reported serious side effects, with behavioral language therapy are recommended.

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.

PubMed

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.

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.

PubMed

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.

Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

PubMed

Heimberger, Amy B; Archer, Gary E; Crotty, Laura E; McLendon, Roger E; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

2002-01-01

Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious. C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII. Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced. In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.

Altered distribution of peripheral blood dendritic cell subsets in patients with pulmonary paracoccidioidomycosis.

PubMed

Venturini, James; Cavalcante, Ricardo Souza; Moris, Daniela Vanessa; Golim, Márjorie de Assis; Levorato, Adriele Dandara; Reis, Karoline Hagatha Dos; Arruda, Maria Sueli Parreira de; Mendes, Rinaldo Poncio

2017-09-01

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi from the genus Paracoccidioides in Latin America. PCM-patients (PCM-p) are classified as having acute/subacute or chronic (CF) clinical forms. CF is responsible for 75%-90% of all cases, affects mainly adults over 30 years old and the clinical manifestation are associated mainly with lungs and mucosa of upper airdigestive tract. In addition, the CF patients exhibit fibrosis of the lungs, oral mucous membranes and adrenals, and pulmonary emphysema. Consequently, CF PCM-p with active disease, as well as those that have been apparently cured, seem to be an interesting model for studies aiming to understand the long-term host-fungi relationship and hypoxia. Dendritic cells (DCs) constitute a system that serve as a major link between innate and adaptive immunity composed of several subpopulations of cells including two main subsets: myeloid (mDCs) and plasmacytoid (pDCs). The present study aimed to access the distribution of PBDC subsets of CF PCM-p who were not treated (NT) or treated (apparently cured - AC). CF PCM-p were categorized into two groups, consisting of 9 NTs and 9 ACs. Twenty-one healthy individuals were used as the control group. The determination of the PBDC subsets was performed by FACS (fluorescence-activated cell sorting) and the dosage of serum TNF-α, IL1β, IL-18, CCL3, IL-10 and basic fibroblast growth factor (bFGF) by ELISA (enzyme-linked immunosorbent assay). A high count and percentage of mDCs was observed before treatment, along with a low count of pDCs in treated patients. Furthermore, the mDC:pDC ratio and serum levels of TNF-α was higher in both of the PCM-p groups than in the control group. In conclusion, our findings demonstrated that active PCM influences the distribution of mDCs and pDCs, and after treatment, PCM-p retained a lower count of pDCs associated with pro-inflammatory profile. Therefore, we identified new evidences of persistent immunological abnormalities in PCM-p after treatment. Even these patients showing fungal clearance after successful antifungal treatment; the hypoxia, triggered by the persistent pulmonary sequelae, possibly continues to interfere in the immune response. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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.

[Damage control in field surgery].

PubMed

Samokhvalov, I M; Manukovskiĭ, V A; Badalov, V I; Severin, V V; Golovko, K P; Denisenko, V V

2011-09-01

Damage control surgery (DCS) is an important option in the store of war surgery and surgery of trauma. The main purpose of our investigation was to specify the percentage of the injured who need DCS. We performed retrospective study of the patients in the combat operations in Chechnya (1994-2002) and in peacetime (2005-2010). Total lethality in group with the standard surgical approach was 62.3%. It was significantly higher than the lethality in group of patients who underwent DCS - 50.0% (p < 0.05). Thus, the experience of DCS in War Surgery Department confirms that DCS is perspective tendency in treatment of patients with severe and extremely severe trauma, and allows decreasing lethality in 12.3%.

IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells

PubMed Central

Lee, Hyang-Mi; Fleige, Anne; Forman, Ruth; Cho, Sunglim; Khan, Aly Azeem; Lin, Ling-Li; Nguyen, Duc T.; O'Hara-Hall, Aisling; Yin, Zhinan; Hunter, Christopher A.; Muller, Werner; Lu, Li-Fan

2015-01-01

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. PMID:25658840

Frequency of Dendritic Cells and Their Expression of Costimulatory Molecules in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Saad, Khaled; Zahran, Asmaa M.; Elsayh, Khalid I.; Abdel-Rahman, Ahmed A.; Al-Atram, Abdulrahman A.; Hussein, Almontaser; El-Gendy, Yasmin G.

2017-01-01

The aim of our study was to evaluate the frequencies of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) in children with ASD. Subjects were 32 children with ASD and 30 healthy children as controls. The numbers of mDCs and pDCs and the expression of CD86 and CD80 on the entire DCs were detected by flow cytometry. ASD children…

GM-CSF Monocyte-Derived Cells and Langerhans Cells As Part of the Dendritic Cell Family

PubMed Central

Lutz, Manfred B.; Strobl, Herbert; Schuler, Gerold; Romani, Nikolaus

2017-01-01

Dendritic cells (DCs) and macrophages (Mph) share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs), the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs) or human CD14+ peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs). The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function. PMID:29109731

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

PubMed

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 < 0.001) and 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.

Differential effects of primary motor cortex and cerebellar transcranial direct current stimulation on motor learning in healthy individuals: A randomized double-blind sham-controlled study.

PubMed

Ehsani, F; Bakhtiary, A H; Jaberzadeh, S; Talimkhani, A; Hajihasani, A

2016-11-01

The purpose of study was to compare the effect of primary motor cortex (M1) and cerebellar anodal transcranial direct current stimulation (a-tDCS) on online and offline motor learning in healthy individuals. Fifty-nine healthy volunteers were randomly divided into three groups (n=20 in two experimental groups and n=19 in sham-control group). One experimental group received M1a-tDCSand another received cerebellar a-tDCS. The main outcome measure were response time (RT) and number of errors during serial response time test (SRTT) which were assessed prior, 35min and 48h after the interventions. Reduction of response time (RT) and error numbers at last block of the test compared to the first block was considered online learning. Comparison of assessments during retention tests was considered as short-term and long-term offline learning. Online RT reduction was not different among groups (P>0.05), while online error reduction was significantly greater in cerebellar a-tDCS than sham-control group (P<0.017). Moreover, a-tDCS on both M1 and cerebellar regions produced more long-term offline learning as compared to sham tDCS (P<0.01), while short-term offline RT reduction was significantly greater in M1a-tDCS than sham-control group (P<0.05). The findings indicated that although cerebellar a-tDCS enhances online learning and M1a-tDCS has more effect on short-term offline learning, both M 1 and cerebellar a-tDCS can be used as a boosting technique for improvement of offline motor learning in healthy individuals. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Mast Cells Condition Dendritic Cells to Mediate Allograft Tolerance

PubMed Central

de Vries, Victor C.; Pino-Lagos, Karina; Nowak, Elizabeth C.; Bennett, Kathy A.; Oliva, Carla; Noelle, Randolph J.

2013-01-01

SUMMARY Peripheral tolerance orchestrated by regulatory T cells, dendritic cells (DCs), and mast cells (MCs) has been studied in several models including skin allograft tolerance. We now define a role for MCs in controlling DC behavior (“conditioning”) to facilitate tolerance. Under tolerant conditions, we show that MCs mediated a marked increase in tumor necrosis factor (TNFα)-dependent accumulation of graft-derived DCs in the dLN compared to nontolerant conditions. This increase of DCs in the dLN is due to the local production of granulocyte macrophage colony-stimulating factor (GM-CSF) by MCs that induces a survival advantage of graft-derived DCs. DCs that migrated to the dLN from the tolerant allograft were tolerogenic; i.e., they dominantly suppress T cell responses and control regional immunity. This study underscores the importance of MCs in conditioning DCs to mediate peripheral tolerance and shows a functional impact of peripherally produced TNFα and GM-CSF on the migration and function of tolerogenic DCs. PMID:22035846

Chromatin remodeling modulates radiosensitivity of the daughter cells derived from cell population exposed to low- and high-LET irradiation

PubMed Central

Chen, Xiaoyan; Zhu, Lin; Zhang, Hang; Wang, Chen; Shao, Chunlin

2017-01-01

Radiation effects are dependent of linear energy transfer (LET), but it is still obscure whether the daughter cells (DCs) derived from irradiated population are radioresistance and much less the underlying mechanism. With the measurements of survival, proliferation and γH2AX foci, this study shows that the DCs from γ-ray irradiated cells (DCs-γ) became more radioresistant than its parent control without irradiation, but the radiosensitivity of DCs from α-particle irradiated cells (DCs-α) was not altered. After irradiation with equivalent doses of γ-rays and α-particles, the foci number of histone H3 lysine 9 dimethylation (H3K9me3) and the activity of histone deacetylase (HDAC) in DCs-γ was extensively higher than these in DCs-α and its parent control, indicating that a higher level of heterochromatin was formed in DCs-γ but not in DCs-α. Treatment of cells with SAHA (an inhibitor of HDAC) decreased the level of heterochromatin domains by inhibiting the expressions of H3K9m3 and HP-1a proteins and triggering the expression of acetylated core histone H3 (Ac-H3). When cells were treated with SAHA, the radioresistance phenotype of DCs-γ was eliminated so that the radiosensitivities of DCs-γ, DCs-α and their parent cells approached to same levels. Our current results reveal that γ-rays but not α-particles could induce chromatin remodeling and heterochromatinization which results in the occurrence of radioresistance of DCs, indicating that the combination treatment of irradiation and HDAC inhibitor could serve as a potential cancer therapy strategy, especially for the fraction radiotherapy of low-LET irradiation. PMID:28881774

Change in Mean Frequency of Resting-State Electroencephalography after Transcranial Direct Current Stimulation

PubMed Central

Boonstra, Tjeerd W.; Nikolin, Stevan; Meisener, Ann-Christin; Martin, Donel M.; Loo, Colleen K.

2016-01-01

Transcranial direct current stimulation (tDCS) is proposed as a tool to investigate cognitive functioning in healthy people and as a treatment for various neuropathological disorders. However, the underlying cortical mechanisms remain poorly understood. We aim to investigate whether resting-state electroencephalography (EEG) can be used to monitor the effects of tDCS on cortical activity. To this end we tested whether the spectral content of ongoing EEG activity is significantly different after a single session of active tDCS compared to sham stimulation. Twenty participants were tested in a sham-controlled, randomized, crossover design. Resting-state EEG was acquired before, during and after active tDCS to the left dorsolateral prefrontal cortex (15 min of 2 mA tDCS) and sham stimulation. Electrodes with a diameter of 3.14 cm2 were used for EEG and tDCS. Partial least squares (PLS) analysis was used to examine differences in power spectral density (PSD) and the EEG mean frequency to quantify the slowing of EEG activity after stimulation. PLS revealed a significant increase in spectral power at frequencies below 15 Hz and a decrease at frequencies above 15 Hz after active tDCS (P = 0.001). The EEG mean frequency was significantly reduced after both active tDCS (P < 0.0005) and sham tDCS (P = 0.001), though the decrease in mean frequency was smaller after sham tDCS than after active tDCS (P = 0.073). Anodal tDCS of the left DLPFC using a high current density bi-frontal electrode montage resulted in general slowing of resting-state EEG. The similar findings observed following sham stimulation question whether the standard sham protocol is an appropriate control condition for tDCS. PMID:27375462

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).

PubMed

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.

Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study.

PubMed

Borckardt, Jeffrey J; Romagnuolo, Joseph; Reeves, Scott T; Madan, Alok; Frohman, Heather; Beam, Will; George, Mark S

2011-06-01

Emerging evidence shows that transcranial direct current stimulation (tDCS), a minimally invasive brain stimulation technique, has analgesic effects in chronic pain patients and in healthy volunteers with experimental pain. No studies have examined the analgesic effects of tDCS immediately after surgical/endoscopic procedures. Endoscopy investigating abdominal pain, especially ERCP, can cause significant postprocedural pain. To test the feasibility, efficacy, and safety of tDCS on post-ERCP pain and analgesia use. Randomized, sham-controlled, pilot study. Tertiary-care medical center. This study involved 21 patients who were hospitalized overnight for ERCP for unexplained right upper quadrant pain. Twenty minutes of real 2.0 mA tDCS or sham (anode over left prefrontal cortex; cathode over gut-representation of right sensory cortex) immediately after ERCP. Pain (visual analogue scale, McGill pain questionnaire, brief pain inventory), patient-controlled analgesia use, adverse events. Real tDCS was associated with 22% less total hydromorphone use, versus sham. The slope of the cumulative patient-controlled analgesia usage curve was significantly steeper in the sham tDCS group (F [2,13] = 15.96; P = .0003). Real tDCS patients reported significantly less pain interference with sleep (t [17] = 3.70; P = .002) and less throbbing pain (t [16] = 2.37; P = .03). Visual analogue scale pain and mood scores (4 hours post-ERCP) suggested a nonsignificant advantage for real tDCS, despite less hydromorphone use. Side effects of tDCS were limited to mild, self-limited tingling, itching, and stinging under electrodes. Small sample size, variability in chronic pain, and chronic opioid use. In this pilot study, tDCS appears to be safe, has minimal side effects, and may reduce postprocedural analgesia requirements and subjective pain ratings. Future studies appear warranted. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia

PubMed Central

Ding, Zhaofeng; Li, Jinrong; Spiegel, Daniel P.; Chen, Zidong; Chan, Lily; Luo, Guangwei; Yuan, Junpeng; Deng, Daming; Yu, Minbin; Thompson, Benjamin

2016-01-01

Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia. PMID:26763954

The effect of transcranial direct current stimulation on contrast sensitivity and visual evoked potential amplitude in adults with amblyopia.

PubMed

Ding, Zhaofeng; Li, Jinrong; Spiegel, Daniel P; Chen, Zidong; Chan, Lily; Luo, Guangwei; Yuan, Junpeng; Deng, Daming; Yu, Minbin; Thompson, Benjamin

2016-01-14

Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia.

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

NASA Astrophysics Data System (ADS)

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.

Decline in Immunological Responses Mediated by Dendritic Cells in Mice Treated with 18α-Glycyrrhetinic Acid.

PubMed

Ebrahimnezhad, Salimeh; Amirghofran, Zahra; Karimi, Mohammad Hossein

2016-01-01

18α-Glycyrrhetinic acid (18α-GA), a bioactive component of Glycyrrhiza glabra, has been shown in vitro immunomodulatory effects on dendritic cells (DCs). The aim of the present study is to evaluate the in vivo effect of 18α-GA on DCs and T cell responses. 18α-GA was intraperitoneally administered to mice and splenic DCs were evaluated for expression of co-stimulatory molecules using flow cytometry. Isolated DCs were added to mixed lymphocyte reaction (MLR) and the proliferation of T cells was measured using BrdU assay. The level of IFN-γ in the MLR supernatant was determined by enzyme-linked immunosorbent assay. The in vivo effect of isolated DCs on antigen-specific delayed type hypersensitivity (DTH) response, and the number of regulatory T (Treg) cells in mice spleen by flow cytometry, were investigated. DCs isolated from 18α-GA-treated mice expressed lower levels of CD40 (p < 0.05) and MHC II (p < 0.01) compared to those of control group. In MLR assay isolated DCs decreased T cell proliferation to 83.54% ± 4.3% of control (p < 0.05). The level of IFN-γ in the MLR supernatant was declined to 25.2% ± 6.8% of control. In DTH test, DCs isolated from 18α-GA-treated mice significantly suppressed antigen-specific cell mediated immune response (3.3 ± 1 mm in test group versus 6.5 ± 1.2 mm in control group, ρ < 0.01). The percentage of Treg cells in spleen of 18α-GA-treated mice (6.37% ± 2.3%) was lower than that of control group (13.85% ± 0.4%, ρ < 0.05). In vivo administration of 18α-GA resulted in inhibition of DCs maturation and T cell-mediated responses, the effects that may candidate this compound for its possible benefits in immune-mediated diseases.

Thoracic Inlet Parameters for Degenerative Cervical Spondylolisthesis Imaging Measurement.

PubMed

Wang, Quanbing; Wang, Xiao-Tao; Zhu, Lei; Wei, Yu-Xi

2018-04-05

BACKGROUND The aim of this study was to explore the diagnostic value of sagittal measurement of thoracic inlet parameters for degenerative cervical spondylolisthesis (DCS). MATERIAL AND METHODS We initially included 65 patients with DCS and the same number of health people as the control group by using cervical radiograph evaluations. We analyzed the x-ray and computer tomographic (CT) data in prone and standing position at the same time. Measurement of cervical sagittal parameters was carried out in a standardized supine position. Multivariate logistic regression analysis was performed to evaluate these parameters as a diagnostic index for DCS. RESULTS There were 60 cases enrolled in the DCS group, and 62 cases included in the control group. The T1 slope and thoracic inlet angle (TIA) were significantly greater for the DCS group compared to the control group (24.33±2.85º versus 19.59±2.04º, p=0.00; 76.11±9.82º versus 72.86±7.31º, p=0.03, respectively). We observed no significant difference for the results of the neck tilt (NT), C2-C7 angle in the control and the DSC group (p>0.05). Logistic regression analysis and receiver operating characteristic (ROC) curve revealed that preoperative T1 slope of more than 22.0º showed significantly diagnostic value for the DCS group (p<0.05). CONCLUSIONS Patients with preoperative sagittal imbalance of thoracic inlet have a statistically significant increased risk of DCS. T1 slope of more than 22.0º showed significantly diagnostic value for the incidence of DCS.

The Space Technology-7 Disturbance Reduction System Precision Control Flight Validation Experiment Control System Design

NASA Technical Reports Server (NTRS)

O'Donnell, James R.; Hsu, Oscar C.; Maghami, Peirman G.; Markley, F. Landis

2006-01-01

As originally proposed, the Space Technology-7 Disturbance Reduction System (DRS) project, managed out of the Jet Propulsion Laboratory, was designed to validate technologies required for future missions such as the Laser Interferometer Space Antenna (LISA). The two technologies to be demonstrated by DRS were Gravitational Reference Sensors (GRSs) and Colloidal MicroNewton Thrusters (CMNTs). Control algorithms being designed by the Dynamic Control System (DCS) team at the Goddard Space Flight Center would control the spacecraft so that it flew about a freely-floating GRS test mass, keeping it centered within its housing. For programmatic reasons, the GRSs were descoped from DRS. The primary goals of the new mission are to validate the performance of the CMNTs and to demonstrate precise spacecraft position control. DRS will fly as a part of the European Space Agency (ESA) LISA Pathfinder (LPF) spacecraft along with a similar ESA experiment, the LISA Technology Package (LTP). With no GRS, the DCS attitude and drag-free control systems make use of the sensor being developed by ESA as a part of the LTP. The control system is designed to maintain the spacecraft s position with respect to the test mass, to within 10 nm/the square root of Hz over the DRS science frequency band of 1 to 30 mHz.

The effect of simulated weightlessness on hypobaric decompression sickness

NASA Technical Reports Server (NTRS)

Balldin, Ulf I.; Pilmanis, Andrew A.; Webb, James T.

2002-01-01

BACKGROUND: A discrepancy exists between the incidence of ground-based decompression sickness (DCS) during simulated extravehicular activity (EVA) at hypobaric space suit pressure (20-40%) and crewmember reports during actual EVA (zero reports). This could be due to the effect of gravity during ground-based DCS studies. HYPOTHESIS: At EVA suit pressures of 29.6 kPa (4.3 psia), there is no difference in the incidence of hypobaric DCS between a control group and group exposed to simulated weightlessness (supine body position). METHODS: Male subjects were exposed to a hypobaric pressure of 29.6 kPa (4.3 psi) for up to 4 h. The control group (n = 26) pre-oxygenated for 60 min (first 10 min exercising) before hypobaric exposure and walking around in the altitude chamber. The test group (n = 39) remained supine for a 3 h prior to and during the 60-min pre-oxygenation (also including exercise) and at hypobaric pressure. DCS symptoms and venous gas emboli (VGE) at hypobaric pressure were registered. RESULTS: DCS occurred in 42% in the control and in 44% in simulated weightlessness group (n.s.). The mean time for DCS to develop was 112 min (SD +/- 61) and 123 min (+/- 67), respectively. VGE occurred in 81% of the control group subjects and in 51% of the simulated weightlessness subjects (p = 0.02), while severe VGE occurred in 58% and 33%, respectively (p = 0.08). VGE started after 113 min (+/- 43) in the control and after 76 min (+/- 64) in the simulated weightlessness group. CONCLUSIONS: No difference in incidence of DCS was shown between control and simulated weightlessness conditions. VGE occurred more frequently during the control condition with bubble-releasing arm and leg movements.

Knowledge-based operation and management of communications systems

NASA Technical Reports Server (NTRS)

Heggestad, Harold M.

1988-01-01

Expert systems techniques are being applied in operation and control of the Defense Communications System (DCS), which has the mission of providing reliable worldwide voice, data and message services for U.S. forces and commands. Thousands of personnel operate DCS facilities, and many of their functions match the classical expert system scenario: complex, skill-intensive environments with a full spectrum of problems in training and retention, cost containment, modernization, and so on. Two of these functions are: (1) fault isolation and restoral of dedicated circuits at Tech Control Centers, and (2) network management for the Defense Switched Network (the modernized dial-up voice system currently replacing AUTOVON). An expert system for the first of these is deployed for evaluation purposes at Andrews Air Force Base, and plans are being made for procurement of operational systems. In the second area, knowledge obtained with a sophisticated simulator is being embedded in an expert system. The background, design and status of both projects are described.

Knowledge-based operation and management of communications systems

NASA Astrophysics Data System (ADS)

Heggestad, Harold M.

1988-11-01

Expert systems techniques are being applied in operation and control of the Defense Communications System (DCS), which has the mission of providing reliable worldwide voice, data and message services for U.S. forces and commands. Thousands of personnel operate DCS facilities, and many of their functions match the classical expert system scenario: complex, skill-intensive environments with a full spectrum of problems in training and retention, cost containment, modernization, and so on. Two of these functions are: (1) fault isolation and restoral of dedicated circuits at Tech Control Centers, and (2) network management for the Defense Switched Network (the modernized dial-up voice system currently replacing AUTOVON). An expert system for the first of these is deployed for evaluation purposes at Andrews Air Force Base, and plans are being made for procurement of operational systems. In the second area, knowledge obtained with a sophisticated simulator is being embedded in an expert system. The background, design and status of both projects are described.

Impact of HBeAg on the maturation and function of dendritic cells.

PubMed

Lan, Songsong; Wu, Lecan; Wang, Xiuyan; Wu, Jinming; Lin, Xianfan; Wu, Wenzhi; Huang, Zhiming

2016-05-01

HBV infection typically leads to chronic hepatitis in newborns and some adults with weakened immune systems. The mechanisms by which virus escapes immunity remain undefined. Regulatory dendritic cells (DCregs) contributing to immune escape have been described. We wondered whether or not HBeAg as an immunomodulatory protein could induce DCreg which might subsequently result into HBV persistence. The immunophenotyping, T-cell activation and cytokine production were analyzed in HBeAg-treated DCs from normal or cyclophosphamide (Cy)-induced immunocompromised mice. HBeAg tended to promote bone marrow derived DCs (BMDCs) from Cy-treated mice into CD11b(high)PIR-B(+) regulatory DCs exhibiting the lowest T-cell stimulatory capacity and interleukin (IL)-12p70 production compared with controls. Neutralization of IL-10 significantly inhibited the regulatory effect of these DCs on T-cell stimulation of mature DCs. After lipopolysaccharides (LPS) stimulation, marked phosphorylation of Akt was detected in HBeAg treated DCs from immunocompromised mice. Blocking the PI3K-Akt pathway by LY294002 led to an enhancement of IL-12 production. PI3K signalling pathway appears to be involved in the decreased IL-12 secretion by HBeAg treated DCs. These findings suggest that HBeAg may program the generation of a new DC subset with regulatory capacity under the condition of immunosuppression, which may presumably contribute to the persistent HBV infection. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β.

PubMed

Alamino, Vanina A; Mascanfroni, Iván D; Montesinos, María M; Gigena, Nicolás; Donadio, Ana C; Blidner, Ada G; Milotich, Sonia I; Cheng, Sheue-Yann; Masini-Repiso, Ana M; Rabinovich, Gabriel A; Pellizas, Claudia G

2015-04-01

Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8(+) T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy. ©2015 American Association for Cancer Research.

Transvertebral direct current stimulation paired with locomotor training in chronic spinal cord injury: A case study.

PubMed

Powell, Elizabeth Salmon; Carrico, Cheryl; Raithatha, Ravi; Salyers, Emily; Ward, Andrea; Sawaki, Lumy

2016-01-01

This double-blind, sham-controlled, crossover case study combined transvertebral direct current stimulation (tvDCS) and locomotor training on a robot-assisted gait orthosis (LT-RGO). Determine whether cathodal tvDCS paired with LT-RGO leads to greater changes in function and neuroplasticity than sham tvDCS paired with LT-RGO. University of Kentucky (UK) HealthCare Stroke and Spinal Cord Neurorehabilitation Research at HealthSouth Cardinal Hill Hospital. A single subject with motor incomplete spinal cord injury (SCI) participated in 24 sessions of sham tvDCS paired with LT-RGO before crossover to 24 sessions of cathodal tvDCS paired with LT-RGO. Functional outcomes were measured with 10 Meter Walk Test (10MWT), 6 Minute Walk Test (6MWT), Spinal Cord Independence Measure-III (SCIM-III) mobility component, lower extremity manual muscle test (MMT), and Berg Balance Scale (BBS). Corticospinal changes were assessed using transcranial magnetic stimulation. Improvement in 10MWT speed, SCIM-III mobility component, and BBS occurred with both conditions. 6MWT worsened after sham tvDCS and improved after cathodal tvDCS. MMT scores for both lower extremities improved following sham tvDCS but decreased following cathodal tvDCS. Corticospinal excitability increased following cathodal tvDCS but not sham tvDCS. These results suggest that combining cathodal tvDCS and LT-RGO may improve functional outcomes, increase corticospinal excitability, and possibly decrease spasticity. Randomized controlled trials are needed to confirm these conclusions. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and the HealthSouth Cardinal Hill Stroke and Spinal Cord Endowment (1215375670).

Effect of porcine circovirus type 2 (PCV2) on the function of splenic CD11c+ dendritic cells in mice.

PubMed

Wang, Xiaobo; Chen, Ligong; Yuan, Wanzhe; Li, Yanqin; Li, Limin; Li, Tanqing; Li, Huanrong; Song, Qinye

2017-05-01

Porcine circovirus-associated disease (PCVAD) caused by porcine circovirus type 2 (PCV2) is an important disease in the global pig industry. Dendritic cells (DCs) are the primary immune cells capable of initiating adaptive immune responses as well as major target cells of PCV2. To determine whether PCV2 affects the immune functions of DCs, we evaluated the expression of endocytosis and co-stimulatory molecules on DCs (CD11c + ) from PCV2-infected mouse spleen by flow cytometry (FCM). We also analyzed the main cytokines secreted by DCs (CD11c + ) and activation of CD4 + and CD8 + T cells by DCs (CD11c + ) through measurement of cytokine secretion, using ELISA. Compared with control mice, PCV2 did not affect the endocytic activity of DCs but it significantly enhanced TNF-α secretion and markedly decreased IFN-α secretion. Subsets of CD40 + , MHCII + CD40 + and CD137L + CD86 + DCs did not increase obviously, but MHCII + CD40 - and CD137L - CD80 + /CD86 + DCs increased significantly in PCV2-infected mouse spleen. Under the stimulation of DCs from PCV2-infected mouse, secretion of IFN-γ by CD4 + and CD8 + T cells and of IL-12 by CD8 + T cells was significantly lower than in control mice, while secretion of IL-4 by CD4 + T cells was remarkably higher. These results indicate that PCV2 modulates cytokine secretion and co-stimulatory molecule expression of DCs, and alters activation of CD4 + and CD8 + T cells by DCs. The immunomodulatory effects of PCV2 on DCs might be related to the host's immune dysfunction and persistent infection with this virus.

No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia: A Double-Blind, Randomized Controlled Trial.

PubMed

Hofmeijer-Sevink, Mieke Klein; Duits, Puck; Rijkeboer, Marleen M; Hoogendoorn, Adriaan W; van Megen, Harold J; Vulink, Nienke C; Denys, Damiaan A; van den Hout, Marcel A; van Balkom, Anton J; Cath, Danielle C

2017-10-01

D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the effectiveness of adding 125 mg of DCS to exposure therapy (before or directly after the first 6 treatment sessions) in patients with panic disorder with agoraphobia and (2) the effectiveness of DCS augmentation preceding exposure relative to DCS augmentation directly postexposure. Fifty-seven patients were allocated to 1 of 3 medication conditions (placebo and pre-exposure and postexposure DCS) as an addition to 6 exposure sessions within a 12-session exposure and response prevention protocol. The primary outcome measure was the mean score on the "alone" subscale of the Mobility Inventory (MI). No differences were found in treatment outcome between DCS and placebo, administered either pre-exposure or postexposure therapy, although at 3-month follow-up, the DCS postexposure group compared with DCS pre-exposure, exhibited greater symptom reduction on the MI-alone subscale. Ancillary analyses in specific subgroups (responders vs nonresponders, early vs late responders, severely vs mildly affected patients) did not reveal any between-group DCS versus placebo differences. Finally, the study did not find an effect of DCS relative to placebo to be specific for successful exposure sessions. This study does not find an effect of augmentation with DCS in patients with severe panic disorder and agoraphobia administered either pretreatment or directly posttreatment sessions. Moreover, no preferential effects are revealed in specific subgroups nor in successful exposure sessions. Yet, a small effect of DCS administration postexposure therapy cannot be ruled out, given the relatively small sample size of this study.

Reduced Current Spread by Concentric Electrodes in Transcranial Electrical Stimulation (tES).

PubMed

Bortoletto, M; Rodella, C; Salvador, R; Miranda, P C; Miniussi, C

2016-01-01

We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Data relay system specifications for ERTS image interpretation

NASA Technical Reports Server (NTRS)

Daniel, J. F.

1970-01-01

Experiments with the Data Collection System (DCS) of the Earth Resources Technology Satellites (ERTS) have been developed to stress ERTS applications in the Earth Resources Observation Systems (EROS) Program. Active pursuit of this policy has resulted in the design of eight specific experiments requiring a total of 98 DCS ground-data platforms. Of these eight experiments, six are intended to make use of DCS data as an aid in image interpretation, while two make use of the capability to relay data from remote locations. Preliminary discussions regarding additional experiments indicate a need for at least 150 DCS platforms within the EROS Program for ERTS experimentation. Results from the experiments will be used to assess the DCS suitability for satellites providing on-line, real-time, data relay capability. The rationale of the total DCS network of ground platforms and the relationship of each experiment to that rationale are discussed.

System Control for the Transitional DCS.

DTIC Science & Technology

1979-07-01

ELEMENT. PROJI Honeywell System and Research Center AREA & WORK UNIT NUMBE Aerospace and Defense Group 2700 Ridgway Parkway, Minneapolis,MN 55413 It1...performance monitoring and stress isolation system for the terrestrial transmission system. The satellite system is assumed to be under the control of its...the routing tables could be in a failed condition while some other route, although less efficient, is still functioning. The recommended adaptive

Dendritic cells in uninfected infants born to hepatitis B virus-positive mothers.

PubMed

Koumbi, Lemonica J; Papadopoulos, Nikolaos G; Anastassiadou, Vassiliki; Machaira, Maria; Kafetzis, Dimitris A; Papaevangelou, Vassiliki

2010-07-01

Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-alpha) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-alpha production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-alpha production until the age of 6 months and inhibits IFN-alpha responses triggered by the TLR7 pathway.

Cyclophosphamide induces bone marrow to yield higher numbers of precursor dendritic cells in vitro capable of functional antigen presentation to T cells in vivo

PubMed Central

Salem, Mohamed L.; El-Naggar, Sabry A.; Cole, David J.

2009-01-01

We have shown recently that cyclophosphamide (CTX) treatment induced a marked increase in the numbers of immature dendritic cells (DCs) in blood, coinciding with enhanced antigen-specific responses of the adoptively transferred CD8+ T cells. Because this DC expansion was preceded by DC proliferation in bone marrow (BM), we tested whether BM post CTX treatment can generate higher numbers of functional DCs. BM was harvested three days after treatment of C57BL/6 mice with PBS or CTX and cultured with GM-CSF/IL-4 in vitro. Compared with control, BM from CTX-treated mice showed faster generation and yielded higher numbers of DCs with superior activation in response to toll-like receptor (TLR) agonists. Vaccination with peptide-pulsed DCs generated from BM from CTX-treated mice induced comparable adjuvant effects to those induced by control DCs. Taken together, post CTX BM harbors higher numbers of DC precursors capable of differentiating into functional DCs, which be targeted to create host microenvironment riches in activated DCs upon treatment with TLR agonists. PMID:20036354

Colloid Microthruster Flight Performance Results from Space Technology 7 Disturbance Reduction System

NASA Technical Reports Server (NTRS)

Ziemer, John; Marrese-Reading, Colleen; Dunn, Charley; Romero-Wolf, Andrew; Cutler, Curt; Javidnia, Shahram; Li, Thanh; Li, Irena; Franklin, Garth; Barela, Phil;

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

Lukhanin, Gennadiy; Biery, Kurt; Foulkes, Stephen

In the NO A experiment, the Detector Controls System (DCS) provides a method for controlling and monitoring important detector hardware and environmental parameters. It is essential for operating the detector and is required to have access to roughly 370,000 independent programmable channels via more than 11,600 physical devices. In this paper, we demonstrate an application of Control System Studio (CSS), developed by Oak Ridge National Laboratory, for the NO A experiment. The application of CSS for the DCS of the NO A experiment has been divided into three phases: (1) user requirements and concept prototype on a test-stand, (2) smallmore » scale deployment at the prototype Near Detector on the Surface, and (3) a larger scale deployment at the Far Detector. We also give an outline of the CSS integration with the NO A online software and the alarm handling logic for the Front-End electronics.« less

A case-control study evaluating relative risk factors for decompression sickness: a research report.

PubMed

Suzuki, Naoko; Yagishita, Kazuyosi; Togawa, Seiichiro; Okazaki, Fumihiro; Shibayama, Masaharu; Yamamoto, Kazuo; Mano, Yoshihiro

2014-01-01

Factors contributing to the pathogenesis of decompression sickness (DCS) in divers have been described in many studies. However, relative importance of these factors has not been reported. In this case-control study, we compared the diving profiles of divers experiencing DCS with those of a control group. The DCS group comprised 35 recreational scuba divers who were diagnosed by physicians as having DCS. The control group consisted of 324 apparently healthy recreational divers. All divers conducted their dives from 2009 to 2011. The questionnaire consisted of 33 items about an individual's diving profile, physical condition and activities before, during and just after the dive. To simplify dive parameters, the dive site was limited to Izu Osezaki. Odds ratios and multiple logistic regression were used for the analysis. Odds ratios revealed several items as dive and health factors associated with DCS. The major items were as follows: shortness of breath after heavy exercise during the dive (OR = 12.12), dehydration (OR = 10.63), and maximum dive depth > 30 msw (OR = 7.18). Results of logistic regression were similar to those by odds ratio analysis. We assessed the relative weights of the surveyed dive and health factors associated with DCS. Because results of several factors conflict with previous studies, future studies are needed.

Polarity-dependent improvement of maximal-effort sprint cycling performance by direct current stimulation of the central nervous system.

PubMed

Sasada, Syusaku; Endoh, Takashi; Ishii, Tomoya; Komiyama, Tomoyoshi

2017-09-14

Sprint motor performance, such as in short-distance running or cycling, gradually decreases after reaching a maximum speed or cadence. This may be attributed to the central nervous system. Brain stimulation studies have recently revealed the plastic nature of the human brain and spinal cord, but it is unclear how direct current stimulation (DCS) affects sprint motor performance. To address this issue, we investigated DCS's effect on healthy volunteers' sprint cycling performance. DCS was applied to the lumbar spinal cord (3mA) or the leg area of the motor cortex (2mA) for 15min with 3 different polarities: anodal, cathodal, and sham. After DCS, the subjects performed maximal-effort sprint cycling for 30s under a constant load. Pooled mean power during the 30s was significantly greater after cathodal transcutaneous spinal DCS to the lumbar spinal cord (tsDCS) than anodal or sham tsDCS. The improvement with cathodal stimulation was notable both 0-5 and 20-25s after the performance onset. There were no significant inter-conditional differences in peak power. Pooled mean power was significantly greater after anodal transcranial DCS to the motor cortex (tDCS) than after cathodal tDCS, although mean powers of anodal and sham tDCS were not significantly different. The increase in mean power after cathodal tsDCS could result from a reduction in central fatigue. This stimulus method might improve sprint performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice.

PubMed

Liu, Chengwen; Lou, Yanyan; Lizée, Gregory; Qin, Hong; Liu, Shujuan; Rabinovich, Brian; Kim, Grace J; Wang, Yi-Hong; Ye, Yang; Sikora, Andrew G; Overwijk, Willem W; Liu, Yong-Jun; Wang, Gang; Hwu, Patrick

2008-03-01

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-gamma production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells.

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin

PubMed Central

2012-01-01

Background Dendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo. Methods Blood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry. Results Administration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations – CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 – one of the major costimulatory molecules – neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes. Conclusions In the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo. PMID:23199104

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Puła, Bartosz; Krawczyk-Rusiecka, Kinga; Zygmunt, Arkadiusz; Borowiecka, Magdalena; Dzięgiel, Piotr; Lewiński, Andrzej

2012-11-30

Dendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo. Blood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry. Administration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations - CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 - one of the major costimulatory molecules - neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes. In the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo.

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

PubMed Central

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

Molecular control of steady-state dendritic cell maturation and immune homeostasis.

PubMed

Hammer, Gianna Elena; Ma, Averil

2013-01-01

Dendritic cells (DCs) are specialized sentinels responsible for coordinating adaptive immunity. This function is dependent upon coupled sensitivity to environmental signs of inflammation and infection to cellular maturation-the programmed alteration of DC phenotype and function to enhance immune cell activation. Although DCs are thus well equipped to respond to pathogens, maturation triggers are not unique to infection. Given that immune cells are exquisitely sensitive to the biological functions of DCs, we now appreciate that multiple layers of suppression are required to restrict the environmental sensitivity, cellular maturation, and even life span of DCs to prevent aberrant immune activation during the steady state. At the same time, steady-state DCs are not quiescent but rather perform key functions that support homeostasis of numerous cell types. Here we review these functions and molecular mechanisms of suppression that control steady-state DC maturation. Corruption of these steady-state operatives has diverse immunological consequences and pinpoints DCs as potent drivers of autoimmune and inflammatory disease.

Null tDCS Effects in a Sustained Attention Task: The Modulating Role of Learning

PubMed Central

Jacoby, Noa; Lavidor, Michal

2018-01-01

The purpose of this study was to investigate sustained attention through modulation of the fronto-cerebral network with transcranial direct current stimulation (tDCS) in adults with attention-deficit/hyperactivity disorder (ADHD) and control participants. Thirty-seven participants (21 with ADHD) underwent three separate sessions (baseline, active tDCS, and sham) and performed the MOXO Continuous Performance Test (CPT). We applied double anodal stimulation of 1.8 mA tDCS for 20 min over the left and right dorsolateral prefrontal cortex (DLPFC), with the cathode over the cerebellum. Baseline session revealed significant differences between ADHD and control participants in the MOXO-CPT attention and hyperactivity scores, validating the MOXO as a diagnostic tool. However, there were no tDCS effects in most MOXO-CPT measures, except hyperactivity, due to a significant learning effect. We conclude that learning and repetition effects in cognitive tasks need to be considered when designing within-subjects tDCS experiments, as there are natural improvements between sessions that conceal potential stimulation effects. PMID:29681876

Null tDCS Effects in a Sustained Attention Task: The Modulating Role of Learning.

PubMed

Jacoby, Noa; Lavidor, Michal

2018-01-01

The purpose of this study was to investigate sustained attention through modulation of the fronto-cerebral network with transcranial direct current stimulation (tDCS) in adults with attention-deficit/hyperactivity disorder (ADHD) and control participants. Thirty-seven participants (21 with ADHD) underwent three separate sessions (baseline, active tDCS, and sham) and performed the MOXO Continuous Performance Test (CPT). We applied double anodal stimulation of 1.8 mA tDCS for 20 min over the left and right dorsolateral prefrontal cortex (DLPFC), with the cathode over the cerebellum. Baseline session revealed significant differences between ADHD and control participants in the MOXO-CPT attention and hyperactivity scores, validating the MOXO as a diagnostic tool. However, there were no tDCS effects in most MOXO-CPT measures, except hyperactivity, due to a significant learning effect. We conclude that learning and repetition effects in cognitive tasks need to be considered when designing within-subjects tDCS experiments, as there are natural improvements between sessions that conceal potential stimulation effects.

Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8.

PubMed

Ah Kioon, Marie Dominique; Tripodo, Claudio; Fernandez, David; Kirou, Kyriakos A; Spiera, Robert F; Crow, Mary K; Gordon, Jessica K; Barrat, Franck J

2018-01-10

Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the secretion of CXCL4 is under the control of phosphatidylinositol 3-kinase δ and is due to the aberrant presence of TLR8 on pDCs of SSc patients, which is not seen in healthy donors or in lupus pDCs, and that CXCL4 primarily acts by potentiating TLR8- but also TLR9-induced IFN production by pDCs. Depleting pDCs prevented disease in a mouse model of scleroderma and could revert fibrosis in mice with established disease. In contrast, the disease was exacerbated in mice transgenic for TLR8 with recruitment of pDCs to the fibrotic skin, whereas TLR7 only partially contributed to the inflammatory response, indicating that TLR8 is the key RNA-sensing TLR involved in the establishment of fibrosis. We conclude that the pDC is an essential cell type involved in the pathogenesis of SSc and its removal using depleting antibodies or attenuating pDC function could be a novel approach to treat SSc patients. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The effect of the perfluorocarbon emulsion Oxycyte on platelet count and function in the treatment of decompression sickness in a swine model.

PubMed

Cronin, William A; Senese, Angela L; Arnaud, Francoise G; Regis, David P; Auker, Charles R; Mahon, Richard T

2016-09-01

Decompression from elevated ambient pressure is associated with platelet activation and decreased platelet counts. Standard treatment for decompression sickness (DCS) is hyperbaric oxygen therapy. Intravenous perfluorocarbon (PFC) emulsion is a nonrecompressive therapy being examined that improves mortality in animal models of DCS. However, PFC emulsions are associated with a decreased platelet count. We used a swine model of DCS to study the effect of PFC therapy on platelet count, function, and hemostasis. Castrated male swine (n = 50) were fitted with a vascular port, recovered, randomized, and compressed to 180 feet of sea water (fsw) for 31 min followed by decompression at 30 fsw/min. Animals were observed for DCS, administered 100% oxygen, and treated with either emulsified PFC Oxycyte (DCS-PFC) or isotonic saline (DCS-NS). Controls underwent the same procedures, but were not compressed (Sham-PFC and Sham-NS). Measurements of platelet count, thromboelastometry, and coagulation were obtained 1 h before compression and 1, 24, 48, 96, 168 and 192 h after treatment. No significant changes in normalized platelet counts were observed. Prothrombin time was elevated in DCS-PFC from 48 to 192 h compared with DCS-NS, and from 96 to 192 h compared with Sham-PFC. Normalized activated partial thromboplastin time was also elevated in DCS-PFC from 168 to 192 h compared with Sham-PFC. No bleeding events were noted. DCS treated with PFC (Oxycyte) does not impact platelet numbers, whole blood clotting by thromboelastometry, or clinical bleeding. Late changes in prothrombin time and activated partial thromboplastin time associated with PFC use in both DCS therapy and controls warrant further investigation.

Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

PubMed

Fricke, K; Seeber, A A; Thirugnanasambandam, N; Paulus, W; Nitsche, M A; Rothwell, J C

2011-03-01

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

Transcranial Direct Current Stimulation of Frontal Cortex Decreases Performance on the WAIS-IV Intelligence Test

PubMed Central

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

2015-01-01

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 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, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). 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. PMID:25934490

Combined Transcranial Direct Current Stimulation and Vision Restoration Training in Subacute Stroke Rehabilitation: A Pilot Study.

PubMed

Alber, Raimund; Moser, Hermann; Gall, Carolin; Sabel, Bernhard A

2017-08-01

Visual field defects after posterior cerebral artery stroke can be improved by vision restoration training (VRT), but when combined with transcranial direct current stimulation (tDCS), which alters brain excitability, vision recovery can be potentiated in the chronic stage. To date, the combination of VRT and tDCS has not been evaluated in postacute stroke rehabilitation. To determine whether combined tDCS and VRT can be effectively implemented in the early recovery phase following stroke, and to explore the feasibility, safety and efficacy of an early intervention. Open-label pilot study including a case series of 7 tDCS/VRT versus a convenience sample of 7 control patients (ClinicalTrials.gov ID: NCT02935413). Rehabilitation center. Patients with homonymous visual field defects following a posterior cerebral artery stroke. Seven homonymous hemianopia patients were prospectively treated with 10 sessions of combined tDCS (2.mA, 10 daily sessions of 20 minutes) and VRT at 66 (±50) days on average poststroke. Visual field recovery was compared with the retrospective data of 7 controls, whose defect sizes and age of lesions were matched to those of the experimental subjects and who had received standard rehabilitation with compensatory eye movement and exploration training. All 7 patients in the treatment group completed the treatment protocol. The safety and acceptance were excellent, and patients reported occasional skin itching beneath the electrodes as the only minor side effect. Irrespective of their treatment, both groups (treatment and control) showed improved visual fields as documented by an increased mean sensitivity threshold in decibels in standard static perimetry. Recovery was significantly greater (P < .05) in the tDCS/VRT patients (36.73% ± 37.0%) than in the controls (10.74% ± 8.86%). In this open-label pilot study, tDCS/VRT in subacute stroke was demonstrated to be safe, with excellent applicability and acceptance of the treatment. Preliminary effectiveness calculations show that tDCS/VRT may be superior to standard vision training procedures. A confirmatory, larger-sample, controlled, randomized, and double-blind trial is now underway to compare real-tDCS- versus sham-tDCS-supported visual field training in the early vision rehabilitation phase. IV. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Effects of Transcranial Direct Current Stimulation With Sensory Modulation on Stroke Motor Rehabilitation: A Randomized Controlled Trial.

PubMed

Koh, Chia-Lin; Lin, Jau-Hong; Jeng, Jiann-Shing; Huang, Sheau-Ling; Hsieh, Ching-Lin

2017-12-01

To test whether a multistrategy intervention enhanced recovery immediately and longitudinally in patients with severe to moderate upper extremity (UE) paresis. Double-blind, randomized controlled trial with placebo control. Outpatient department of a local medical center. People (N=25) with chronic stroke were randomly assigned to 1 of 2 groups: a transcranial direct current stimulation with sensory modulation (tDCS-SM) group (n=14; mean age ± SD, 55.3±11.4y) or a control group (n=11; mean age ± SD, 56.9±13.5y). Eight-week intervention. The tDCS-SM group received bilateral tDCS, bilateral cutaneous anesthesia, and high repetitions of passive movements on the paretic hand. The control group received the same passive movements but with sham tDCS and sham anesthesia. During the experiment, all participants continued their regular rehabilitation. Voluntary UE movement, spasticity, UE function, and basic activities of daily living. Outcomes were assessed at baseline, at postintervention, and at 3- and 6-month follow-ups. No significant differences were found between groups. However, there was a trend that the voluntary UE movement improved more in the tDCS-SM group than in the control group, with a moderate immediate effect (partial η 2 [η p 2 ]=.14, P=.07) and moderate long-term effects (3-mo follow-up: η p 2 =.17, P=.05; 6-mo follow-up: η p 2 =.12, P=.10). Compared with the control group, the tDCS-SM group had a trend of a small immediate effect (η p 2 =.02-.04) on reducing spasticity, but no long-term effect. A trend of small immediate and long-term effects in favor of tDCS-SM was found on UE function and daily function recovery (η p 2 =.02-.09). Accompanied with traditional rehabilitation, tDCS-SM had a nonsignificant trend of having immediate and longitudinal effects on voluntary UE movement recovery in patients with severe to moderate UE paresis after stroke, but its effects on spasticity reduction and functional recovery may be limited. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Concurrent transcranial direct current stimulation and progressive resistance training in Parkinson's disease: study protocol for a randomised controlled trial.

PubMed

Hendy, Ashlee M; Tillman, Alex; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Kidgell, Dawson J; Wundersitz, Daniel; Enticott, Peter G; Teo, Wei-Peng

2016-07-19

Parkinson's disease (PD) results from a loss of dopamine in the brain, leading to movement dysfunctions such as bradykinesia, postural instability, resting tremor and muscle rigidity. Furthermore, dopamine deficiency in PD has been shown to result in maladaptive plasticity of the primary motor cortex (M1). Progressive resistance training (PRT) is a popular intervention in PD that improves muscular strength and results in clinically significant improvements on the Unified Parkinson's Disease Rating Scale (UPDRS). In separate studies, the application of anodal transcranial direct current stimulation (a-tDCS) to the M1 has been shown to improve motor function in PD; however, the combined use of tDCS and PRT has not been investigated. We propose a 6-week, double-blind randomised controlled trial combining M1 tDCS and PRT of the lower body in participants (n = 42) with moderate PD (Hoehn and Yahr scale score 2-4). Supervised lower body PRT combined with functional balance tasks will be performed three times per week with concurrent a-tDCS delivered at 2 mA for 20 minutes (a-tDCS group) or with sham tDCS (sham group). Control participants will receive standard care (control group). Outcome measures will include functional strength, gait speed and variability, balance, neurophysiological function at rest and during movement execution, and the UPDRS motor subscale, measured at baseline, 3 weeks (during), 6 weeks (post), and 9 weeks (retention). Ethical approval has been granted by the Deakin University Human Research Ethics Committee (project number 2015-014), and the trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001241527). This will be the first randomised controlled trial to combine PRT and a-tDCS targeting balance and gait in people with PD. The study will elucidate the functional, clinical and neurophysiological outcomes of combined PRT and a-tDCS. It is hypothesised that combined PRT and a-tDCS will significantly improve lower limb strength, postural sway, gait speed and stride variability compared with PRT with sham tDCS. Further, we hypothesise that pre-frontal cortex activation during dual-task cognitive and gait/balance activities will be reduced, and that M1 excitability and inhibition will be augmented, following the combined PRT and a-tDCS intervention. Australian New Zealand Clinical Trials Registry ACTRN12615001241527 . Registered on 12 November 2015.

CXCL16-positive dendritic cells enhance invariant natural killer T cell-dependent IFNγ production and tumor control

PubMed Central

Veinotte, Linnea; Gebremeskel, Simon; Johnston, Brent

2016-01-01

ABSTRACT Crosstalk interactions between dendritic cells (DCs) and invariant natural killer T (iNKT) cells are important in regulating antitumor responses elicited by glycolipid antigens. iNKT cells constitutively express the chemokine receptor CXCR6, while cytokine-activated DCs upregulate the transmembrane chemokine ligand, CXCL16. This study examined the co-stimulatory role of CXCR6/CXCL16 interactions in glycolipid-dependent iNKT cell activation and tumor control. Spleen and liver DCs in wild-type mice, but not iNKT cell deficient (Jα18−/−) mice, transiently upregulated surface CXCL16 following in vivo administration of the glycolipid antigen α-galactosylceramide. Recombinant CXCL16 did not directly induce iNKT cell activation in vitro but enhanced interferon (IFN)-γ production when mouse or human iNKT cells were stimulated with plate-bound anti-CD3. Compared with glycolipid-loaded CXCL16neg DCs, CXCL16hi DCs induced higher levels of IFNγ production in iNKT cell cultures and following adoptive transfer in vivo. The number of IFNγ+ iNKT cells and expansion of T-bet+ iNKT cells were reduced in vivo when CXCL16−/− DCs were used to activate iNKT cells. Enhanced IFNγ production in vivo was not dependent on CXCR6 expression on natural killer (NK) cells. Adoptive transfer of glycolipid-loaded CXCL16hi DCs provided superior protection against tumor metastasis compared to CXCL16neg DC transfers. Similarly, wild-type DCs provided superior protection against metastasis compared with CXCL16−/− DCs. These experiments implicate an important role for CXCR6/CXCL16 interactions in regulating iNKT cell IFNγ production and tumor control. The selective use of CXCL16hi DCs in adoptive transfer immunotherapies may prove useful for enhancing T helper (Th) type 1 responses and clinical outcomes in cancer patients. PMID:27471636

Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer

DTIC Science & Technology

2007-12-01

CAR. CD40 is a surface marker expressed by DCs that plays a crucial role in their maturation and subsequent stimulation of T cells. DC infection with... surface . CD40 is a cell surface marker expressed by DCs, is crucial for their maturation and the subsequent activation of the immune system by the DCs...cell surface . CD40 is a cell surface marker expressed by DCs, is crucial for their maturation and the subsequent activation of the immune system by the

Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise.

PubMed

Okano, Alexandre Hideki; Fontes, Eduardo Bodnariuc; Montenegro, Rafael Ayres; Farinatti, Paulo de Tarso Veras; Cyrino, Edilson Serpeloni; Li, Li Min; Bikson, Marom; Noakes, Timothy David

2015-09-01

The temporal and insular cortex (TC, IC) have been associated with autonomic nervous system (ANS) control and the awareness of emotional feelings from the body. Evidence shows that the ANS and rating of perceived exertion (RPE) regulate exercise performance. Non-invasive brain stimulation can modulate the cortical area directly beneath the electrode related to ANS and RPE, but it could also affect subcortical areas by connection within the cortico-cortical neural networks. This study evaluated the effects of transcranial direct current stimulation (tDCS) over the TC on the ANS, RPE and performance during a maximal dynamic exercise. Ten trained cyclists participated in this study (33±9 years; 171.5±5.8 cm; 72.8±9.5 kg; 10-11 training years). After 20-min of receiving either anodal tDCS applied over the left TC (T3) or sham stimulation, subjects completed a maximal incremental cycling exercise test. RPE, heart rate (HR) and R-R intervals (as a measure of ANS function) were recorded continuously throughout the tests. Peak power output (PPO) was recorded at the end of the tests. With anodal tDCS, PPO improved by ~4% (anodal tDCS: 313.2±29.9 vs 301.0±19.8 watts: sham tDCS; p=0.043), parasympathetic vagal withdrawal was delayed (anodal tDCS: 147.5±53.3 vs 125.0±35.4 watts: sham tDCS; p=0.041) and HR was reduced at submaximal workloads. RPE also increased more slowly during exercise following anodal tDCS application, but maximal RPE and HR values were not affected by cortical stimulation. The findings suggest that non-invasive brain stimulation over the TC modulates the ANS activity and the sensory perception of effort and exercise performance, indicating that the brain plays a crucial role in the exercise performance regulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

CD81 controls immunity to Listeria infection through rac-dependent inhibition of proinflammatory mediator release and activation of cytotoxic T cells.

PubMed

Martínez del Hoyo, Gloria; Ramírez-Huesca, Marta; Levy, Shoshana; Boucheix, Claude; Rubinstein, Eric; Minguito de la Escalera, María; González-Cintado, Leticia; Ardavín, Carlos; Veiga, Esteban; Yáñez-Mó, María; Sánchez-Madrid, Francisco

2015-06-15

Despite recent evidence on the involvement of CD81 in pathogen binding and Ag presentation by dendritic cells (DCs), the molecular mechanism of how CD81 regulates immunity during infection remains to be elucidated. To investigate the role of CD81 in the regulation of defense mechanisms against microbial infections, we have used the Listeria monocytogenes infection model to explore the impact of CD81 deficiency in the innate and adaptive immune response against this pathogenic bacteria. We show that CD81(-/-) mice are less susceptible than wild-type mice to systemic Listeria infection, which correlates with increased numbers of inflammatory monocytes and DCs in CD81(-/-) spleens, the main subsets controlling early bacterial burden. Additionally, our data reveal that CD81 inhibits Rac/STAT-1 activation, leading to a negative regulation of the production of TNF-α and NO by inflammatory DCs and the activation of cytotoxic T cells by splenic CD8α(+) DCs. In conclusion, this study demonstrates that CD81-Rac interaction exerts an important regulatory role on the innate and adaptive immunity against bacterial infection and suggests a role for CD81 in the development of novel therapeutic targets during infectious diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Brain Switches Utilitarian Behavior: Does Gender Make the Difference?

PubMed Central

Fumagalli, Manuela; Vergari, Maurizio; Pasqualetti, Patrizio; Marceglia, Sara; Mameli, Francesca; Ferrucci, Roberta; Mrakic-Sposta, Simona; Zago, Stefano; Sartori, Giuseppe; Pravettoni, Gabriella; Barbieri, Sergio; Cappa, Stefano; Priori, Alberto

2010-01-01

Decision often implies a utilitarian choice based on personal gain, even at the expense of damaging others. Despite the social implications of utilitarian behavior, its neurophysiological bases remain largely unknown. To assess how the human brain controls utilitarian behavior, we delivered transcranial direct current stimulation (tDCS) over the ventral prefrontal cortex (VPC) and over the occipital cortex (OC) in 78 healthy subjects. Utilitarian judgment was assessed with the moral judgment task before and after tDCS. At baseline, females provided fewer utilitarian answers than males for personal moral dilemmas (p = .007). In males, VPC-tDCS failed to induce changes and in both genders OC-tDCS left utilitarian judgments unchanged. In females, cathodal VPC-tDCS tended to decrease whereas anodal VPC-tDCS significantly increased utilitarian responses (p = .005). In males and females, reaction times for utilitarian responses significantly decreased after cathodal (p<.001) but not after anodal (p = .735) VPC-tDCS. We conclude that ventral prefrontal tDCS interferes with utilitarian decisions, influencing the evaluation of the advantages and disadvantages of each option in both sexes, but does so more strongly in females. Whereas cathodal tDCS alters the time for utilitarian reasoning in both sexes, anodal stimulation interferes more incisively in women, modifying utilitarian reasoning and the possible consequent actions. The gender-related tDCS-induced changes suggest that the VPC differentially controls utilitarian reasoning in females and in males. The gender-specific functional organization of the brain areas involved in utilitarian behavior could be a correlate of the moral and social behavioral differences between the two sexes. PMID:20111608

Effect of transcranial direct current stimulation (tDCS) during complex whole body motor skill learning.

PubMed

Kaminski, Elisabeth; Hoff, Maike; Sehm, Bernhard; Taubert, Marco; Conde, Virginia; Steele, Christopher J; Villringer, Arno; Ragert, Patrick

2013-09-27

The aim of the study was to investigate tDCS effects on motor skill learning in a complex whole body dynamic balance task (DBT). We hypothesized that tDCS over the supplementary motor area (SMA), a region that is known to be involved in the control of multi-joint whole body movements, will result in polarity specific changes in DBT learning. In a randomized sham-controlled, double-blinded parallel design, we applied 20 min of tDCS over the supplementary motor area (SMA) and prefrontal cortex (PFC) while subjects performed a DBT. Anodal tDCS over SMA with the cathode placed over contralateral PFC impaired motor skill learning of the DBT compared to sham. This effect was still present on the second day of training. Reversing the polarity (cathode over SMA, anode over PFC) did not affect motor skill learning neither on the first nor on the second day of training. To better disentangle whether the impaired motor skill learning was due to a modulation of SMA or PFC, we performed an additional control experiment. Here, we applied anodal tDCS over SMA together with a larger and presumably more ineffective electrode (cathode) over PFC. Interestingly this alternative tDCS electrode setup did not affect the outcome of DBT learning. Our results provide novel evidence that a modulation of the (right) PFC seems to impair complex multi-joint motor skill learning. Hence, future studies should take the positioning of both tDCS electrodes into account when investigating complex motor skill learning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Identification of Barramundi (Lates calcarifer) DC-SCRIPT, a Specific Molecular Marker for Dendritic Cells in Fish

PubMed Central

Zoccola, Emmanuelle; Delamare-Deboutteville, Jérôme; Barnes, Andrew C.

2015-01-01

Antigen presentation is a critical step bridging innate immune recognition and specific immune memory. In mammals, the process is orchestrated by dendritic cells (DCs) in the lymphatic system, which initiate clonal proliferation of antigen-specific lymphocytes. However, fish lack a classical lymphatic system and there are currently no cellular markers for DCs in fish, thus antigen-presentation in fish is poorly understood. Recently, antigen-presenting cells similar in structure and function to mammalian DCs were identified in various fish, including rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio). The present study aimed to identify a potential molecular marker for DCs in fish and therefore targeted DC-SCRIPT, a well-conserved zinc finger protein that is preferentially expressed in all sub-types of human DCs. Putative dendritic cells were obtained in culture by maturation of spleen and pronephros-derived monocytes. DC-SCRIPT was identified in barramundi by homology using RACE PCR and genome walking. Specific expression of DC-SCRIPT was detected in barramundi cells by Stellaris mRNA FISH, in combination with MHCII expression when exposed to bacterial derived peptidoglycan, suggesting the presence of DCs in L. calcarifer. Moreover, morphological identification was achieved by light microscopy of cytospins prepared from these cultures. The cultured cells were morphologically similar to mammalian and trout DCs. Migration assays determined that these cells have the ability to move towards pathogens and pathogen associated molecular patterns, with a preference for peptidoglycans over lipopolysaccharides. The cells were also strongly phagocytic, engulfing bacteria and rapidly breaking them down. Barramundi DCs induced significant proliferation of responder populations of T-lymphocytes, supporting their role as antigen presenting cells. DC-SCRIPT expression in head kidney was higher 6 and 24 h following intraperitoneal challenge with peptidoglycan and lipopolysaccharide and declined after 3 days relative to PBS-injected controls. Relative expression was also lower in the spleen at 3 days post challenge but increased again at 7 days. As DC-SCRIPT is a constitutively expressed nuclear receptor, independent of immune activation, this may indicate initial migration of immature DCs from head kidney and spleen to the injection site, followed by return to the spleen for maturation and antigen presentation. DC-SCRIPT may be a valuable tool in the investigation of antigen presentation in fish and facilitate optimisation of vaccines and adjuvants for aquaculture. PMID:26173015

Applications of ERTS-A Data Collection System (DCS) in the Arizona Regional Ecological Test Site (ARETS)

NASA Technical Reports Server (NTRS)

Schumann, H. H. (Principal Investigator)

1972-01-01

The author has identified the following significant results. Preliminary analysis of DCS data from the USGS Verde River stream flow measuring site indicates the DCS system is furnishing high quality data more frequently than had been expected. During the 43-day period between Nov. 3, and Dec. 15, 1972, 552 DCS transmissions were received during 193 data passes. The amount of data received far exceeded the single high quality transmission per 12-hour period expected from the DCS system. The digital-parallel ERTS-1 data has furnished sufficient to accurately compute mean daily gage heights. These in turn, are used to compute average daily streamflow rates during periods of stable or slowly changing flow conditions. The digital-parallel data has also furnished useful information during peak flow periods. However, the serial-digital DCS capability, currently under development for transmitting streamflow data, should provide data of greater utility for determining times of flood peaks.

Detector Control System for the AFP detector in ATLAS experiment at CERN

NASA Astrophysics Data System (ADS)

Banaś, E.; Caforio, D.; Czekierda, S.; Hajduk, Z.; Olszowska, J.; Seabra, L.; Šícho, P.

2017-10-01

The ATLAS Forward Proton (AFP) detector consists of two forward detectors located at 205 m and 217 m on either side of the ATLAS experiment. The aim is to measure the momenta and angles of diffractively scattered protons. In 2016, two detector stations on one side of the ATLAS interaction point were installed and commissioned. The detector infrastructure and necessary services were installed and are supervised by the Detector Control System (DCS), which is responsible for the coherent and safe operation of the detector. A large variety of used equipment represents a considerable challenge for the AFP DCS design. Industrial Supervisory Control and Data Acquisition (SCADA) product Siemens WinCCOA, together with the CERN Joint Control Project (JCOP) framework and standard industrial and custom developed server applications and protocols are used for reading, processing, monitoring and archiving of the detector parameters. Graphical user interfaces allow for overall detector operation and visualization of the detector status. Parameters, important for the detector safety, are used for alert generation and interlock mechanisms.

Application and outcomes of therapy combining transcranial direct current stimulation and virtual reality: a systematic review.

PubMed

Massetti, Thais; Crocetta, Tânia Brusque; Silva, Talita Dias da; Trevizan, Isabela Lopes; Arab, Claudia; Caromano, Fátima Aparecida; Monteiro, Carlos Bandeira de Mello

2017-08-01

To evaluate the methods and major outcomes of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) therapy in randomized controlled trials. A systematic review was performed following PRISMA guidelines using PubMed, PubMed Central, Web of Science and CAPES periodic databases, with no time restriction. The studies were screened for the following inclusion criteria: human subjects, combination of VR and tDCS methods, and randomized controlled study design. All potentially relevant articles were independently reviewed by two researchers, who reached a consensus on which articles met the inclusion criteria. The PEDro scale was used to evaluate the studies. Eleven studies were included, all of which utilized a variety of tDCS and VR application methods. The main outcomes were found to be beneficial in intervention groups of different populations, including improvements in body sway, gait, stroke recovery, pain management and vegetative reactions. The use of tDCS combined with VR showed positive results in both healthy and impaired patients. Future studies with larger sample sizes and homogeneous participants are required to confirm the benefits of tDCS and VR. Implications for Rehabilitation tDCS with VR intervention can be an alternative to traditional rehabilitation programs. tDCS with VR is a promising type of intervention with a variety of positive effects. Application of tDCS with VR is appropriated to both healthy and impaired patients. There is no consensus of tDCS with VR application.

Regulatory Dendritic Cells.

PubMed

Sato, Katsuaki; Uto, Tomofumi; Fukaya, Tomohiro; Takagi, Hideaki

2017-01-01

Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines. On the other hand, treatment of DCs with certain immunosuppressive drugs and molecules leads to the generation of tolerogenic DCs that show downregulation of both the major histocompatibility complex (MHC) and costimulatory molecules, and not only show defective T-cell activation, but also possess tolerogenic properties including the induction of anergic T-cells and regulatory T (T reg ) cells. To develop an effective strategy for Ag-specific intervention of T-cell-mediated immune disorders, we have previously established the modified DCs with moderately high levels of MHC molecules that are defective in the expression of costimulatory molecules that had a greater immunoregulatory property than classical tolerogenic DCs, which we therefore designated as regulatory DCs (DC reg ). Herein, we integrate the current understanding of the role of DCs in the control of immune responses, and further provide new information of the characteristics of tolerogenic DCs and DC reg , as well as their regulation of immune responses and disorders.

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

PubMed

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.

Dexmedetomidine Inhibits Maturation and Function of Human Cord Blood-Derived Dendritic Cells by Interfering with Synthesis and Secretion of IL-12 and IL-23

PubMed Central

Chen, Gong; Le, Yuan; Zhou, Lei; Gong, Li; Li, Xiaoxiao; Li, Yunli; Liao, Qin; Duan, Kaiming; Tong, Jianbin; Ouyang, Wen

2016-01-01

Aims To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs). Methods Human DCs and cytotoxic T lymphocytes (CTLs) were obtained from human cord blood mononuclear cells by density gradient centrifugation. Cultured DCs were divided into three groups: dexmedetomidine group, dexmedetomidine plus yohimbine (dexmedetomidine inhibitor) group and control group. DCs in the three groups were treated with dexmedetomidine, dexmedetomidine plus yohimbine and culture medium, respectively. After washing, the DCs were co-incubated with cultured CTLs. The maturation degree of DCs was evaluated by detecting (1) the ratios of HLA-DR-, CD86-, and CD80-positive cells (flow cytometry), and (2) expression of IL-12 and IL-23 (PCR and Elisa). The function of DCs was evaluated by detecting the proliferation (MTS assay) and cytotoxicity activity (the Elisa of IFN-γ) of CTLs. In addition, in order to explore the mechanisms of dexmedetomidine modulating DCs, α2-adrenergic receptor and its downstream signals in DCs were also detected. Results The ratios of HLA-DR-, CD86-, and CD80-positive cells to total cells were similar among the three groups (P>0.05). Compared to the control group, the protein levels of IL-12 and IL-23 in the culture medium and the mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the DCs all decreased in dexmedetomidine group (P<0.05). In addition, the proliferation of CTLs and the secretion of IFN-γ also decreased in the dexmedetomidine group, compared with the control group (P<0.05). Moreover, these changes induced by dexmedetomidine in the dexmedetomidine group were reversed by α2-adrenergic receptor inhibitor yohimbine in the dexmedetomidine plus yohimbine group. It was also found the decrease of mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the dexmedetomidine group could be reversed by ERK1/2 or AKT inhibitors. Conclusion Dexmedetomidine could negatively modulate human immunity by inhibiting the maturation of DCs and then decreasing the proliferation and cytotoxicity activity of CTLs. The α2-adrenergic receptors and its downstream molecules ERK1/2 and AKT are closely involved in the modulation of dexmedetomidine on DCs. PMID:27054340

Cumulative and booster effects of tdcs sessions on drug cravings, lapse, and cognitive impairment in methamphetamine use disorder: A case study report.

PubMed

Shariatirad, Schwann; Vaziri, Alaleh; Hassani-Abharian, Peyman; Sharifi Fardshad, Mona; Molavi, Nader; Fitzgerald, Paul B

2016-06-01

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation method, which shows promising therapeutic effects in controlling drug cravings. In this study, we present cumulative and booster effects of tDCS sessions on methamphetamine cravings, lapse, and cognitive impairment in a methamphetamine dependent subject. Our study shows cumulative effects of continuous anodal tDCS sessions on right dorsolateral prefrontal cortex (DLPFC) could reduce drug cravings and their consequences. Moreover, booster tDCS treatments might be helpful in controlling psychological stress and drug cravings. (Am J Addict 2016;25:264-266). © 2016 American Academy of Addiction Psychiatry.

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

Dirske, R.D.; Hauck, P.C.; Kachmar, R.P.

In 1990, the federal government enacted the Clean Air Amendment. This required many public power utilities across the country to make modifications to their fossil fueled power plants to comply with the mandated emission levels by May 1995. At Pennsylvania Electric Company`s (PENELEC) Shawville Station, Units 3 and 4, the mandates established maximum nitrogen oxides (NOx) emission levels at 0.45 lbs/MMBTU. In an effort to comply with the new reduced emission levels, PENELEC chose to implement the Asea Brown Boveri-Combustion Engineering`s (ABB-CE) Low NOx Concentric Firing System III (LNCFS-III). PENELEC also took this opportunity to replace other controls because theirmore » implementation would have relatively little impact on the overall cost of the project and would enhance the ability of the operators to better control NOx emissions. This paper discusses the implementation of the new controls in a distributed control system (DCS), interfacing the DCS with the existing pneumatic combustion controls, and maintaining the boiler control benchboard as the primary operator interface, thereby, reducing the impact of the changes to the MMI and the overall cost of the project.« less

Biologic Potential of Calcium Phosphate Biopowders Produced via Decomposition Combustion Synthesis

PubMed Central

Vollmer, N.; King, K.B.; Ayers, R.

2015-01-01

The aim of this research was to evaluate the biologic potential of calcium phosphate (CaP) biopowders produced with a novel reaction synthesis system. Decomposition combustion synthesis (DCS) is a modified combustion synthesis method capable of producing CaP powders for use in bone tissue engineering applications. During DCS, the stoichiometric ratio of reactant salt to fuel was adjusted to alter product chemistry and morphology. In vitro testing methods were utilized to determine the effects of controlling product composition on cytotoxicity, proliferation, biocompatibility and biomineralization. In vitro, human fetal osteoblasts (ATCC, CRL-11372) cultured with CaP powder displayed a flattened morphology, and uniformly encompassed the CaP particulates. Matrix vesicles containing calcium and phosphorous budded from the osteoblast cells. CaP powders produced via DCS are a source of biologically active, synthetic, bone graft substitute materials PMID:26034341

Effects of transcranial direct current stimulation on esophageal motility in patients with gastroesophageal reflux disease.

PubMed

Vigneri, Simone; Bonventre, Sebastiano; Inviati, Angela; Schifano, Domenico; Cosentino, Giuseppe; Puma, Angela; Giglia, Giuseppe; Paladino, Piera; Brighina, Filippo; Fierro, Brigida

2014-09-01

To evaluate the effects of transcranial direct current stimulation (tDCS) on esophageal peristalsis in patients with gastroesophageal reflux disease (GERD). Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study. Esophageal manometry was performed before and during transcranial direct current stimulation (tDCS) of the right precentral cortex. Half of patients were randomly assigned to anodal, half to sham stimulation. Distal waves amplitude and pathological waves percentage were measured, after swallowing water boli, for ten subsequent times. Last, a 24h pH-bilimetry was done to diagnose non-erosive reflux disease (NERD) or functional heartburn (FH). The values obtained before and during anodal or sham tDCS were compared. Sixty-eight patients were enrolled in the study. Distal waves mean amplitude increased significantly only during anodal tDCS in NERD (p=0.00002) and FH subgroups (p=0.008) while percentage of pathological waves strongly decreased only in NERDs (p=0.002). Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease (ERD) patients. Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well. In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells.

PubMed

Ménager, Mickaël M

2017-06-15

Dendritic cells (DCs) have essential roles in early detection of pathogens and activation of both innate and adaptive immune responses. Whereas human DCs are resistant to productive HIV-1 replication, they have a unique ability to take up virus and transmit it efficiently to T lymphocytes. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. While performing an shRNA screen in human primary monocyte-derived DCs, to gain insights into this cell biological process, we discovered the role played by tetraspanin-7 (TSPAN7). This member of the tetraspanin family appears to be a positive regulator of actin nucleation and stabilization, through the ARP2/3 complex. By doing so, TSPAN7 limits HIV-1 endocytosis and maintains viral particles on actin-rich dendrites for an efficient transfer toward T lymphocytes. While studying the function of TSPAN7 in the control of actin nucleation, we also discovered the existence in DCs of two opposing forces at the plasma membrane: actin nucleation, a protrusive force which seems to counterbalance actomyosin contraction. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis.

PubMed

Cruzat, Andrea; Witkin, Deborah; Baniasadi, Neda; Zheng, Lixin; Ciolino, Joseph B; Jurkunas, Ula V; Chodosh, James; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram

2011-07-11

To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the "in vivo" nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm(2); P < 0.0001), fungal (608.9 ± 812.5 cells/mm(2); P < 0.0001), and Acanthamoeba keratitis (1000.2 ± 1090.3 cells/mm(2); P < 0.0001) compared with controls (49.3 ± 39.6 cells/mm(2)). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 ± 976.1 vs. 3913.9 ± 507.4 μm/frame), total nerve numbers (2.7 ± 3.9 vs. 20.2 ± 3.3), main trunks (1.5 ± 2.2 vs. 6.9 ± 1.1), and branching (1.2 ± 2.0 vs. 13.5 ± 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r = -0.44; P < 0.0005). IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea.

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

PubMed

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.

Minocycline promotes the generation of dendritic cells with regulatory properties.

PubMed

Kim, Narae; Park, Chan-Su; Im, Sun-A; Kim, Ji-Wan; Lee, Jae-Hee; Park, Young-Jun; Song, Sukgil; Lee, Chong-Kil

2016-08-16

Minocycline, which has long been used as a broad-spectrum antibiotic, also exhibits non-antibiotic properties such as inhibition of inflammation and angiogenesis. In this study, we show that minocycline significantly enhances the generation of dendritic cells (DCs) from mouse bone marrow (BM) cells when used together with GM-CSF and IL-4. DCs generated from BM cells in the presence of minocycline (Mino-DCs) demonstrate the characteristics of regulatory DCs. Compared with control DCs, Mino-DCs are resistant to subsequent maturation stimuli, impaired in MHC class II-restricted exogenous Ag presentation, and show decreased cytokine secretion. Mino-DCs also show decreased ability to prime allogeneic-specific T cells, while increasing the expansion of CD4+CD25+Foxp3+ T regulatory cells both in vitro and in vivo. In addition, pretreatment with MOG35-55 peptide-pulsed Mino-DCs ameliorates clinical signs of experimental autoimmune encephalitis induced by MOG peptide injection. Our study identifies minocycline as a new pharmacological agent that could be potentially used to increase the production of regulatory DCs for cell therapy to treat autoimmune disorders, allergy, and transplant rejection.

Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity.

PubMed

Janelsins, Brian M; Mathers, Alicia R; Tkacheva, Olga A; Erdos, Geza; Shufesky, William J; Morelli, Adrian E; Larregina, Adriana T

2009-03-26

Dendritic cells (DCs) are the preferred targets for immunotherapy protocols focused on stimulation of cellular immune responses. However, regardless of initial promising results, ex vivo generated DCs do not always promote immune-stimulatory responses. The outcome of DC-dependent immunity is regulated by proinflammatory cytokines and neuropeptides. Proinflammatory neuropeptides of the tachykinin family, including substance P (SP) and hemokinin-1 (HK-1), bind the neurokinin 1 receptor (NK1R) and promote stimulatory immune responses. Nevertheless, the ability of pro-inflammatory tachykinins to affect the immune functions of DCs remains elusive. In the present work, we demonstrate that mouse bone marrow-derived DCs (BMDCs) generated in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), express functional NK1R. Signaling via NK1R with SP, HK-1, or the synthetic agonist [Sar(9)Met(O(2))(11)]-SP rescues DCs from apoptosis induced by deprivation of GM-CSF and IL-4. Mechanistic analysis demonstrates that NK1R agonistic binding promotes DC survival via PI3K-Akt signaling cascade. In adoptive transfer experiments, NK1R-signaled BMDCs loaded with Ag exhibit increased longevity in draining lymph nodes, resulting in enhanced and prolonged effector cellular immunity. Our results contribute to the understanding of the interactions between the immune and nervous systems that control DC function and present a novel approach for ex vivo-generation of potent immune-stimulatory DCs.

Topoisomerase I peptide-loaded dendritic cells induce autoantibody response as well as skin and lung fibrosis.

PubMed

Mehta, Heena; Goulet, Philippe-Olivier; Nguyen, Vinh; Pérez, Gemma; Koenig, Martial; Senécal, Jean-Luc; Sarfati, Marika

2016-12-01

DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI. At week 12 after initial DC immunization, TOPOIA DCs but not TOPOIB DCs immunization induced mixed inflammation and fibrosis in lungs and skin. At a late time point (week 18), both TOPOIA DCs and TOPOIB DCs groups displayed increased alpha-smooth muscle actin expression in lungs and dermis along with skin fibrosis distal from the site of injection when compared with unpulsed DCs. Both TopoI peptide-DC-immunized groups developed IgG2a anti-TopoI autoantibody response. At week 10, signs of perivascular, peribronchial, and parenchymal pulmonary inflammation were already observed in the TOPOIA DCs group, together with transient elevation in bronchoalveolar lavage cell counts, IL-17A expression, and CXCL4 production, a biomarker of early human dcSSc. Collectively, TopoI peptide DCs induce progressive autoantibody response as well as development of protracted skin and lung dcSSc-like disease. Pronounced lung inflammation, transient IL-17A, and CXCL4 expression precede fibrosis development. Our immunization strategy, that uses self immune system and autoantigen, will help to further investigate the pathogenesis of this complex autoimmune disorder with unmet medical needs.

Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain

PubMed Central

Anandasabapathy, Niroshana; Victora, Gabriel D.; Meredith, Matthew; Feder, Rachel; Dong, Baojun; Kluger, Courtney; Yao, Kaihui; Dustin, Michael L.; Nussenzweig, Michel C.; Steinman, Ralph M.

2011-01-01

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5–7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia. PMID:21788405

Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain.

PubMed

Anandasabapathy, Niroshana; Victora, Gabriel D; Meredith, Matthew; Feder, Rachel; Dong, Baojun; Kluger, Courtney; Yao, Kaihui; Dustin, Michael L; Nussenzweig, Michel C; Steinman, Ralph M; Liu, Kang

2011-08-01

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5-7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.

Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder.

PubMed

Martin, Donel M; Chan, Herng-Nieng; Alonzo, Angelo; Green, Melissa J; Mitchell, Philip B; Loo, Colleen K

2015-12-01

To investigate the use of transcranial direct current stimulation (tDCS) for enhancing working memory and sustained attention in euthymic patients with bipolar disorder. Fifteen patients with bipolar disorder received anodal left prefrontal tDCS with an extracephalic cathode (prefrontal condition), anodal left prefrontal and cathodal cerebellar tDCS (fronto-cerebellar condition), and sham tDCS given 'online' during performance on a working memory and sustained attention task in an intra-individual, cross-over, sham-controlled experimental design. Exploratory cluster analyses examined responders and non-responders for the different active tDCS conditions on both tasks. For working memory, approximately one-third of patients in both active tDCS conditions showed performance improvement. For sustained attention, three of 15 patients showed performance improvement with prefrontal tDCS. Responders to active tDCS for working memory performed more poorly on the task during sham tDCS compared to non-responders. A single session of active prefrontal or fronto-cerebellar tDCS failed to improve working memory or sustained attention performance in euthymic patients with bipolar disorder. Several important considerations are discussed in relation to future studies investigating tDCS for enhancing cognition in patients with bipolar disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MyD88-dependent dendritic and epithelial cell crosstalk orchestrates immune responses to allergens.

PubMed

Thomas, S Y; Whitehead, G S; Takaku, M; Ward, J M; Xu, X; Nakano, K; Lyons-Cohen, M R; Nakano, H; Gowdy, K M; Wade, P A; Cook, D N

2018-05-01

Sensitization to inhaled allergens is dependent on activation of conventional dendritic cells (cDCs) and on the adaptor molecule, MyD88. However, many cell types in the lung express Myd88, and it is unclear how signaling in these different cell types reprograms cDCs and leads to allergic inflammation of the airway. By combining ATAC-seq with RNA profiling, we found that MyD88 signaling in cDCs maintained open chromatin at select loci even at steady state, allowing genes to be rapidly induced during allergic sensitization. A distinct set of genes related to metabolism was indirectly controlled in cDCs through MyD88 signaling in airway epithelial cells (ECs). In mouse models of asthma, Myd88 expression in ECs was critical for eosinophilic inflammation, whereas Myd88 expression in cDCs was required for Th17 cell differentiation and consequent airway neutrophilia. Thus, both cell-intrinsic and cell-extrinsic MyD88 signaling controls gene expression in cDCs and orchestrates immune responses to inhaled allergens.

Transcranial Direct Current Stimulation in Stroke Rehabilitation: A Review of Recent Advancements

PubMed Central

Gomez Palacio Schjetnan, Andrea; Faraji, Jamshid; Metz, Gerlinde A.; Tatsuno, Masami; Luczak, Artur

2013-01-01

Transcranial direct current stimulation (tDCS) is a promising technique to treat a wide range of neurological conditions including stroke. The pathological processes following stroke may provide an exemplary system to investigate how tDCS promotes neuronal plasticity and functional recovery. Changes in synaptic function after stroke, such as reduced excitability, formation of aberrant connections, and deregulated plastic modifications, have been postulated to impede recovery from stroke. However, if tDCS could counteract these negative changes by influencing the system's neurophysiology, it would contribute to the formation of functionally meaningful connections and the maintenance of existing pathways. This paper is aimed at providing a review of underlying mechanisms of tDCS and its application to stroke. In addition, to maximize the effectiveness of tDCS in stroke rehabilitation, future research needs to determine the optimal stimulation protocols and parameters. We discuss how stimulation parameters could be optimized based on electrophysiological activity. In particular, we propose that cortical synchrony may represent a biomarker of tDCS efficacy to indicate communication between affected areas. Understanding the mechanisms by which tDCS affects the neural substrate after stroke and finding ways to optimize tDCS for each patient are key to effective rehabilitation approaches. PMID:23533955

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

PubMed

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.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer's disease: study protocol for a randomized controlled trial.

PubMed

Cheng, Calvin P W; Chan, Sandra S M; Mak, Arthur D P; Chan, Wai Chi; Cheng, Sheung Tak; Shi, Lin; Wang, Defeng; Lam, Linda Chiu-Wa

2015-10-24

There has been longstanding interesting in cognitive training for older adults with cognitive impairment. In this study, we will investigate the effects of working memory training, and explore augmentation strategies that could possibly consolidate the effects in older adults with mild neurocognitive disorder. Transcranial direct current stimulation (tDCS) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance. As tDCS may also modulate cognitive function through changes in neuroplastic response, it would be adopted as an augmentation strategy for working memory training in the present study. This is a 4-week intervention double-blind randomized controlled trial (RCT) of tDCS. Chinese older adults (aged 60 to 90 years) with mild neurocognitive disorder due to Alzheimer's disease (DSM-5 criteria) would be randomized into a 4-week intervention of either tDCS-working memory (DCS-WM), tDCS-control cognitive training (DCS-CC), and sham tDCS-working memory (WM-CD) groups. The primary outcome would be working memory test - the n-back task performance and the Chinese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Secondary outcomes would be test performance of specific cognitive domains and mood. Intention-to-treat analysis would be carried out. Changes of efficacy indicators with time and intervention would be tested with mixed effect models. This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation, working memory training and dual stimulation in older adults at risk of cognitive decline. It would also examine the tolerability, program adherence and adverse effects of this novel intervention. Information would be helpful for further research of dementia prevention studies. ChiCTR-TRC- 14005036 Date of registration: 31 July 2014.

Anodal Transcranial Direct Current Stimulation Does Not Facilitate Dynamic Balance Task Learning in Healthy Old Adults

PubMed Central

Kaminski, Elisabeth; Hoff, Maike; Rjosk, Viola; Steele, Christopher J.; Gundlach, Christopher; Sehm, Bernhard; Villringer, Arno; Ragert, Patrick

2017-01-01

Older adults frequently experience a decrease in balance control that leads to increased numbers of falls, injuries and hospitalization. Therefore, evaluating older adults’ ability to maintain balance and examining new approaches to counteract age-related decline in balance control is of great importance for fall prevention and healthy aging. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been shown to beneficially influence motor behavior and motor learning. In the present study, we investigated the influence of tDCS applied over the leg area of the primary motor cortex (M1) on balance task learning of healthy elderly in a dynamic balance task (DBT). In total, 30 older adults were enrolled in a cross-sectional, randomized design including two consecutive DBT training sessions. Only during the first DBT session, either 20 min of anodal tDCS (a-tDCS) or sham tDCS (s-tDCS) were applied and learning improvement was compared between the two groups. Our data showed that both groups successfully learned to perform the DBT on both training sessions. Interestingly, between-group analyses revealed no difference between the a-tDCS and the s-tDCS group regarding their level of task learning. These results indicate that the concurrent application of tDCS over M1 leg area did not elicit DBT learning enhancement in our study cohort. However, a regression analysis revealed that DBT performance can be predicted by the kinematic profile of the movement, a finding that may provide new insights for individualized approaches of treating balance and gait disorders. PMID:28197085

Anodal Transcranial Direct Current Stimulation Does Not Facilitate Dynamic Balance Task Learning in Healthy Old Adults.

PubMed

Kaminski, Elisabeth; Hoff, Maike; Rjosk, Viola; Steele, Christopher J; Gundlach, Christopher; Sehm, Bernhard; Villringer, Arno; Ragert, Patrick

2017-01-01

Older adults frequently experience a decrease in balance control that leads to increased numbers of falls, injuries and hospitalization. Therefore, evaluating older adults' ability to maintain balance and examining new approaches to counteract age-related decline in balance control is of great importance for fall prevention and healthy aging. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been shown to beneficially influence motor behavior and motor learning. In the present study, we investigated the influence of tDCS applied over the leg area of the primary motor cortex (M1) on balance task learning of healthy elderly in a dynamic balance task (DBT). In total, 30 older adults were enrolled in a cross-sectional, randomized design including two consecutive DBT training sessions. Only during the first DBT session, either 20 min of anodal tDCS (a-tDCS) or sham tDCS (s-tDCS) were applied and learning improvement was compared between the two groups. Our data showed that both groups successfully learned to perform the DBT on both training sessions. Interestingly, between-group analyses revealed no difference between the a-tDCS and the s-tDCS group regarding their level of task learning. These results indicate that the concurrent application of tDCS over M1 leg area did not elicit DBT learning enhancement in our study cohort. However, a regression analysis revealed that DBT performance can be predicted by the kinematic profile of the movement, a finding that may provide new insights for individualized approaches of treating balance and gait disorders.

Analysis of the individual risk of altitude decompression sickness under repeated exposures

NASA Technical Reports Server (NTRS)

Kumar, K. Vasantha; Horrigan, David J.; Waligora, James M.; Gilbert, John H.

1991-01-01

In a case-control study, researchers examined the risk of decompression sickness (DCS) in individual subjects with higher number of exposures. Of the 126 subjects, 42 showed one or more episodes of DCS. Examination of the exposure-DCS relationship by odds ratio showed a linear relationship. Stratification analysis showed that sex, tissue ratio, and the presence of Doppler microbubbles were cofounders of this risk. A higher number of exposures increased the risk of DCS in this analysis.

Stimulation of Dorsolateral Prefrontal Cortex Enhances Adaptive Cognitive Control: A High-Definition Transcranial Direct Current Stimulation Study.

PubMed

Gbadeyan, Oyetunde; McMahon, Katie; Steinhauser, Marco; Meinzer, Marcus

2016-12-14

Conflict adaptation is a hallmark effect of adaptive cognitive control and refers to the adjustment of control to the level of previously experienced conflict. Conflict monitoring theory assumes that the dorsolateral prefrontal cortex (DLPFC) is causally involved in this adjustment. However, to date, evidence in humans is predominantly correlational, and heterogeneous with respect to the lateralization of control in the DLPFC. We used high-definition transcranial direct current stimulation (HD-tDCS), which allows for more focal current delivery than conventional tDCS, to clarify the causal involvement of the DLPFC in conflict adaptation. Specifically, we investigated the regional specificity and lateralization of potential beneficial stimulation effects on conflict adaptation during a visual flanker task. One hundred twenty healthy participants were assigned to four HD-tDCS conditions: left or right DLPFC or left or right primary motor cortex (M1). Each group underwent both active and sham HD-tDCS in crossover, double-blind designs. We obtained a sizeable conflict adaptation effect (measured as the modulation of the flanker effect as a function of previous response conflict) in all groups and conditions. However, this effect was larger under active HD-tDCS than under sham stimulation in both DLPFC groups. In contrast, active stimulation had no effect on conflict adaptation in the M1 groups. In sum, the present results indicate that the DLPFC plays a causal role in adaptive cognitive control, but that the involvement of DLPFC in control is not restricted to the left or right hemisphere. Moreover, our study confirms the potential of HD-tDCS to modulate cognition in a regionally specific manner. Conflict adaptation is a hallmark effect of adaptive cognitive control. While animal studies have suggested causal involvement of the DLPFC in this phenomenon, such evidence is currently lacking in humans. The present study used high-definition transcranial direct current stimulation (HD-tDCS) to demonstrate that the DLPFC is causally involved in conflict adaptation in humans. Our study confirms a central claim of conflict monitoring theory, which up to now has predominantly relied on correlational studies. Our results further indicate an equal involvement of the left and right DLPFC in adaptive control, whereas stimulation of a control region-the primary motor cortex-had no effect on adaptive control. The study thus confirms the potential of HD-tDCS to modulate cognition in a regionally specific manner. Copyright © 2016 the authors 0270-6474/16/3612530-07$15.00/0.

[Design of a miniaturized blood temperature-varying system based on computer distributed control].

PubMed

Xu, Qiang; Zhou, Zhaoying; Peng, Jiegang; Zhu, Junhua

2007-10-01

Blood temperature-varying has been widely applied in clinical practice such as extracorporeal circulation for whole-body perfusion hyperthermia (WBPH), body rewarming and blood temperature-varying in organ transplantation. This paper reports a novel DCS (Computer distributed control)-based blood temperature-varying system which includes therapy management function and whose hardware and software can be extended easily. Simulation results illustrate that this system provides precise temperature control with good performance in various operation conditions.

Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity.

PubMed

Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A

2016-04-01

Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.

Association of microparticles and neutrophil activation with decompression sickness.

PubMed

Thom, Stephen R; Bennett, Michael; Banham, Neil D; Chin, Walter; Blake, Denise F; Rosen, Anders; Pollock, Neal W; Madden, Dennis; Barak, Otto; Marroni, Alessandro; Balestra, Costantino; Germonpre, Peter; Pieri, Massimo; Cialoni, Danilo; Le, Phi-Nga Jeannie; Logue, Christopher; Lambert, David; Hardy, Kevin R; Sward, Douglas; Yang, Ming; Bhopale, Veena B; Dujic, Zeljko

2015-09-01

Decompression sickness (DCS) is a systemic disorder, assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles (MPs)--vesicular structures with diameters of 0.1-1.0 μm--have been implicated, but data in human divers have been lacking. We hypothesized that the number of blood-borne, Annexin V-positive MPs and neutrophil activation, assessed as surface MPO staining, would differ between self-contained underwater breathing-apparatus divers suffering from DCS vs. asymptomatic divers. Blood was analyzed from 280 divers who had been exposed to maximum depths from 7 to 105 meters; 185 were control/asymptomatic divers, and 90 were diagnosed with DCS. Elevations of MPs and neutrophil activation occurred in all divers but normalized within 24 h in those who were asymptomatic. MPs, bearing the following proteins: CD66b, CD41, CD31, CD142, CD235, and von Willebrand factor, were between 2.4- and 11.7-fold higher in blood from divers with DCS vs. asymptomatic divers, matched for time of sample acquisition, maximum diving depth, and breathing gas. Multiple logistic regression analysis documented significant associations (P < 0.001) between DCS and MPs and for neutrophil MPO staining. Effect estimates were not altered by gender, body mass index, use of nonsteroidal anti-inflammatory agents, or emergency oxygen treatment and were modestly influenced by divers' age, choice of breathing gas during diving, maximum diving depth, and whether repetitive diving had been performed. There were no significant associations between DCS and number of MPs without surface proteins listed above. We conclude that MP production and neutrophil activation exhibit strong associations with DCS. Copyright © 2015 the American Physiological Society.

Online and offline effects of cerebellar transcranial direct current stimulation on motor learning in healthy older adults: a randomized double-blind sham-controlled study.

PubMed

Samaei, Afshin; Ehsani, Fatemeh; Zoghi, Maryam; Hafez Yosephi, Mohaddese; Jaberzadeh, Shapour

2017-05-01

The aim of this randomized double blinded sham-controlled study was to determine the effect of cerebellar anodal transcranial direct current stimulation (a-tDCS) on online and offline motor learning in healthy older individuals. Thirty participants were randomly assigned in experimental (n = 15) or sham tDCS (n = 15) groups. Participants in experimental group received 2 mA cerebellar a-tDCS for 20 min. However, the tDCS was turned off after 30 seconds in sham group. Response time (RT) and error rate (ER) in serial RT test were assessed before, during 35 minutes and 48 h after the intervention. Reduction of RT and ER following the intervention session was considered as short-term (35 min post intervention) and long-term offline learning (48 h post intervention), respectively. Online RT and ER reduction were similar in both groups (P > 0.05). RT was significantly reduced 48 hours post intervention in cerebellar a-tDCS group (P = 0.03). Moreover, RT was significantly increased after 35 minutes and 48 hours in sham tDCS group (P = 0.03, P = 0.007), which indicates a lack of short-term and long-term offline learning in older adults. A-tDCS on cerebellar region produced more short-term and long-term offline improvement in RT (P = 0.014, P = 0.01) compared to sham tDCS. In addition, online, short-term and long-term (48 h) offline error reduced in cerebellar a-tDCS as compared to sham-control group, although this reduction was not significant (P > 0.05). A deficit suggests that a direct comparison to a younger group was made. The findings suggested that cerebellar a-tDCS might be useful for improvement of offline motor learning in older individuals. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity.

PubMed

Chopin, Michaël; Preston, Simon P; Lun, Aaron T L; Tellier, Julie; Smyth, Gordon K; Pellegrini, Marc; Belz, Gabrielle T; Corcoran, Lynn M; Visvader, Jane E; Wu, Li; Nutt, Stephen L

2016-04-26

Plasmacytoid dendritic cells (pDCs) represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-α expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay

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

Yao, Pan; Hongqian, Chu; Qinghe, Meng

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and themore » lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8{sup +} T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. - Highlights: • Lack of TAK1 in DC caused an abolished TCE-induced CHS response. • TAK1 in DCs was essential to maintain the homeostasis of T cells in TCE-induced CHS. • Intact TAK1 in DCs was critical to promote T-cell priming in TCE-induced CHS. • DC-specific TAK1 deficiency abolished the TCE-mediated phosphorylation of Jnk.« less

Transcriptome profile of lung dendritic cells after in vitro porcine reproductive and respiratory syndrome virus (PRRSV) infection

PubMed Central

Pröll, Maren Julia; Neuhoff, Christiane; Schellander, Karl; Uddin, Muhammad Jasim; Cinar, Mehmet Ulas; Sahadevan, Sudeep; Qu, Xueqi; Islam, Md. Aminul; Poirier, Mikhael; Müller, Marcel A.; Drosten, Christian; Tesfaye, Dawit; Tholen, Ernst; Große-Brinkhaus, Christine

2017-01-01

The porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that leads to high financial and production losses in the global swine industry. The pathogenesis of this disease is dependent on a multitude of factors, and its control remains problematic. The immune system generally defends against infectious diseases, especially dendritic cells (DCs), which play a crucial role in the activation of the immune response after viral infections. However, the understanding of the immune response and the genetic impact on the immune response to PRRS virus (PRRSV) remains incomplete. In light of this, we investigated the regulation of the host immune response to PRRSV in porcine lung DCs using RNA-sequencing (RNA-Seq). Lung DCs from two different pig breeds (Pietrain and Duroc) were collected before (0 hours) and during various periods of infection (3, 6, 9, 12, and 24 hours post infection (hpi)). RNA-Seq analysis revealed a total of 20,396 predicted porcine genes, which included breed-specific differentially expressed immune genes. Pietrain and Duroc infected lung DCs showed opposite gene expression courses during the first time points post infection. Duroc lung DCs reacted more strongly and distinctly than Pietrain lung DCs during these periods (3, 6, 9, 12 hpi). Additionally, cluster analysis revealed time-dependent co-expressed groups of genes that were involved in immune-relevant pathways. Key clusters and pathways were identified, which help to explain the biological and functional background of lung DCs post PRRSV infection and suggest IL-1β1 as an important candidate gene. RNA-Seq was also used to characterize the viral replication of PRRSV for each breed. PRRSV was able to infect and to replicate differently in lung DCs between the two mentioned breeds. These results could be useful in investigations on immunity traits in pig breeding and enhancing the health of pigs. PMID:29140992

DCS facilitation of fear extinction and exposure-based therapy may rely on lower-level, automatic mechanisms

PubMed Central

Grillon, Christian

2009-01-01

Exposure-based therapy (EBT), a leading technique in the treatment of a range of anxiety disorders, is facilitated by D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist. This review discusses the potential mechanisms involved in this facilitation, and its implications for developing theories of fear conditioning in humans. Basic research in rodents suggests that DCS acts by speeding up extinction. However, several lab-based investigations found that DCS had no effect on extinction in humans. This paper proposes that these observations can be accounted for by a dual-model theory of fear conditioning in humans that engages two complementary defensive systems: a reflexive lower-order system independent of conscious awareness and a higher-order cognitive system associated with conscious awareness of danger and expectation. DCS studies in animals appear to have explored lower-order conditioning mechanisms, whereas human studies have explored higher-order cognitive processes. These observations suggest that DCS may act preferentially on lower- rather than higher-order learning. This paper presents evidence suggesting that, in humans, DCS may similarly affect lower-order learning during EBT and, consequently, may be less effective during cognitive therapy (e.g., cognitive restructuring). Finally, it is recommended that extinction studies using DCS in humans be conducted using fear-relevant stimuli (e.g., snakes), short conditional stimulus-unconditioned stimulus (CS-US) intervals, and intense US in order to promote lower-order conditioning processes. PMID:19520359

Keeping your armour intact: how HIV-1 evades detection by the innate immune system: HIV-1 capsid controls detection of reverse transcription products by the cytosolic DNA sensor cGAS.

PubMed

Maelfait, Jonathan; Seiradake, Elena; Rehwinkel, Jan

2014-07-01

HIV-1 infects dendritic cells (DCs) without triggering an effective innate antiviral immune response. As a consequence, the induction of adaptive immune responses controlling virus spread is limited. In a recent issue of Immunity, Lahaye and colleagues show that intricate interactions of HIV capsid with the cellular cofactor cyclophilin A (CypA) control infection and innate immune activation in DCs. Manipulation of HIV-1 capsid to increase its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA sensor cGAS to reverse transcribed DNA. This in turn induces a strong host response. Here, we discuss these findings in the context of recent developments in innate immunity and consider the implications for disease control and vaccine design. © 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.

Dual-comb spectroscopy of molecular electronic transitions in condensed phases

NASA Astrophysics Data System (ADS)

Cho, Byungmoon; Yoon, Tai Hyun; Cho, Minhaeng

2018-03-01

Dual-comb spectroscopy (DCS) utilizes two phase-locked optical frequency combs to allow scanless acquisition of spectra using only a single point detector. Although recent DCS measurements demonstrate rapid acquisition of absolutely calibrated spectral lines with unprecedented precision and accuracy, complex phase-locking schemes and multiple coherent averaging present significant challenges for widespread adoption of DCS. Here, we demonstrate Global Positioning System (GPS) disciplined DCS of a molecular electronic transition in solution at around 800 nm, where the absorption spectrum is recovered by using a single time-domain interferogram. We anticipate that this simplified dual-comb technique with absolute time interval measurement and ultrabroad bandwidth will allow adoption of DCS to tackle molecular dynamics investigation through its implementation in time-resolved nonlinear spectroscopic studies and coherent multidimensional spectroscopy of coupled chromophore systems.

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.

PubMed

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.

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.

PubMed

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.

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

PubMed Central

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

2015-01-01

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. PMID:25658925

The type I interferon response during viral infections: a "SWOT" analysis.

PubMed

Gaajetaan, Giel R; Bruggeman, Cathrien A; Stassen, Frank R

2012-03-01

The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll-like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths-Weaknesses-Opportunities-Threats ("SWOT") analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system. Copyright © 2011 John Wiley & Sons, Ltd.

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.

PubMed

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.

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

PubMed Central

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

Epifluorescence Intravital Microscopy of Murine Corneal Dendritic Cells

PubMed Central

Rosenbaum, James T.; Planck, Stephen R.

2010-01-01

Purpose. Dendritic cells (DCs) are antigen-presenting cells vital for initiating immune responses. In this study the authors examined the in vivo migratory capability of resident corneal DCs to various stimuli. Methods. The authors used mice expressing enhanced yellow fluorescent protein (eYFP) under control of the CD11c promoter to visualize corneal DCs. To assess the distribution and mobility of DCs, normal corneas were imaged in vivo and ex vivo with fluorescence microscopy. Intravital microscopy was used to examine the responses of resident central and peripheral corneal DCs to silver nitrate injury, lipopolysaccharide, microspheres, and tumor necrosis factor (TNF-α). In some experiments, TNF-α injection was used to first induce centripetal migration of DCs to the central cornea, which was subsequently reinjected with microspheres. Results. In normal corneas, DCs were sparsely distributed centrally and were denser in the periphery, with epithelial-level DCs extending into the epithelium. Videomicroscopy showed that though cell processes were in continuous movement, cells generally did not migrate. Within the first 6 hours after stimulation, neither central nor peripheral corneal DCs exhibited significant lateral migration, but central corneal DCs assumed extreme morphologic changes. An increased number of DCs in the TNF-α–stimulated central cornea were responsive to subsequent microsphere injection by adopting a migratory behavior, but not with increased speed. Conclusions. In vivo imaging reveals minimal lateral migration of corneal DCs after various stimuli. In contrast, DCs within the central cornea after initial TNF-α injection are more likely to respond to a secondary insult with lateral migration. PMID:20007837

Dendritic Cell-Based Vaccines that Utilize Myeloid Rather than Plasmacytoid Cells Offer a Superior Survival Advantage in Malignant Glioma.

PubMed

Dey, Mahua; Chang, Alan L; Miska, Jason; Wainwright, Derek A; Ahmed, Atique U; Balyasnikova, Irina V; Pytel, Peter; Han, Yu; Tobias, Alex; Zhang, Lingjiao; Qiao, Jian; Lesniak, Maciej S

2015-07-01

Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-α. Apart from IFN-α production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-α secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4(+)T-bet(+) T cells and CD8(+)SIINFEKEL(+) T cells. This robust antitumor T cell response results in tumor eradication and long-term survival in 60% of the animals (p < 0.001). Copyright © 2015 by The American Association of Immunologists, Inc.

Effects of the addition of transcranial direct current stimulation to virtual reality therapy after stroke: a pilot randomized controlled trial.

PubMed

Viana, R T; Laurentino, G E C; Souza, R J P; Fonseca, J B; Silva Filho, E M; Dias, S N; Teixeira-Salmela, L F; Monte-Silva, K K

2014-01-01

Upper limb (UL) impairment is the most common disabling deficit following a stroke. Previous studies have suggested that transcranial direct current stimulation (tDCS) enhances the effect of conventional therapies. This pilot double-blind randomized control trial aimed to determine whether or not tDCS, combined with Wii virtual reality therapy (VRT), would be superior to Wii therapy alone in improving upper limb function and quality of life in chronic stroke individuals. Twenty participants were randomly assigned either to an experimental group that received VRT and tDCS, or a control group that received VRT and sham tDCS. The therapy was delivered over 15 sessions with 13 minutes of active or sham anodal tDCS, and one hour of virtual reality therapy. The outcomes included were determined using the Fugl-Meyer scale, the Wolf motor function test, the modified Ashworth scale (MAS), grip strength, and the stroke specific quality of life scale (SSQOL). Minimal clinically important differences (MCID) were observed when assessing outcome data. Both groups demonstrated gains in all evaluated areas, except for the SSQOL-UL domain. Differences between groups were only observed in wrist spasticity levels in the experimental group, where more than 50% of the participants achieved the MCID. These findings support that tDCS, combined with VRT therapy, should be investigated and clarified further.

Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.

PubMed

Xia, Yumin; Jiang, Shan; Weng, Shenhong; Lv, Xiaochun; Cheng, Hong; Fang, Chunhong

2011-12-01

Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies. iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-γ produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.

Modulating oscillatory brain activity correlates of behavioral inhibition using transcranial direct current stimulation.

PubMed

Jacobson, Liron; Ezra, Adi; Berger, Uri; Lavidor, Michal

2012-05-01

Studies have mainly documented behavioral changes induced by transcranial direct current stimulation (tDCS), but recently cortical modulations of tDCS have also been investigated. Our previous work revealed behavioral inhibition modulation by anodal tDCS over the right inferior frontal gyrus (rIFG); however, the electrophysiological correlates underlying this stimulation montage have yet to be established. The current work aimed to evaluate the distribution of neuronal oscillations changes following anodal tDCS over rIFG coupled with cathodal tDCS over left orbitofrontal cortex (lOFC) using spectral power analysis. Healthy subjects underwent sham and real tDCS (15 min, 1.5 mA, anodal rIFG; cathodal lOFC) stimulation conditions in a single-blind, placebo-controlled cross-over trial. Following tDCS session, resting EEG recordings were collected during 15 min. Analysis showed a significant and selective diminution of the power of theta band. The theta diminution was observed in the rIFG area (represented the anode electrode), and was not found in the lOFC area (represented the cathode electrode). A significant effect was observed only in the theta but not in other bands. These results are the first demonstration of modulating oscillatory activity as measured by EEG with tDCS over rIFG in general, and documenting theta band reduction with this montage in particular. Our results may explain the improvement in behavioral inhibition reported in our previous work, and although this study was conducted with healthy subjects, the findings suggest that tDCS may also modulate electrophysiological changes among ADHD patients, where decreasing theta activity is the target of neuro-feedback methods aimed to improve cognitive control. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Implication of TLR- but Not of NOD2-Signaling Pathways in Dendritic Cell Activation by Group B Streptococcus Serotypes III and V

PubMed Central

Lemire, Paul; Roy, David; Fittipaldi, Nahuel; Okura, Masatoshi; Takamatsu, Daisuke; Bergman, Eugenia; Segura, Mariela

2014-01-01

Group B Streptococcus (GBS) is an important agent of life-threatening invasive infection. It has been previously shown that encapsulated type III GBS is easily internalized by dendritic cells (DCs), and that this internalization had an impact on cytokine production. The receptors underlying these processes are poorly characterized. Knowledge on the mechanisms used by type V GBS to activate DCs is minimal. In this work, we investigated the role of Toll-like receptor (TLR)/MyD88 signaling pathway, the particular involvement of TLR2, and that of the intracellular sensing receptor NOD2 in the activation of DCs by types III and V GBS. The role of capsular polysaccharide (CPS, one of the most important GBS virulence factors) in bacterial-DC interactions was evaluated using non-encapsulated mutants. Despite differences in the role of CPS between types III and V GBS in bacterial internalization and intracellular survival, no major differences were observed in their capacity to modulate release of cytokines by DC. For both serotypes, CPS had a minor role in this response. Production of cytokines by DCs was shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize GBS and become activated mostly through TLR signaling. Yet, GBS-infected TLR2-/- DCs only showed a partial reduction in the production of IL-6 and CXCL1 compared to control DCs. Surprisingly, CXCL10 release by type III or type V GBS-infected DCs was MyD88-independent. No differences in DC activation were observed between NOD2-/- and control DCs. These results demonstrate the involvement of various receptors and the complexity of the cytokine production pathways activated by GBS upon DC infection. PMID:25436906

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

PubMed

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.

Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

PubMed

Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

2016-02-01

Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality.

PubMed

Yu, Xiao; Cai, Baowei; Wang, Mingjun; Tan, Peng; Ding, Xilai; Wu, Jian; Li, Jian; Li, Qingtian; Liu, Pinghua; Xing, Changsheng; Wang, Helen Y; Su, Xin-Zhuan; Wang, Rong-Fu

2016-11-15

Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β (IFN-α/β) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/β production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted. Further, we identified SOCS1 as a key negative regulator to inhibit MyD88-dependent type I IFN signaling in pDCs. Finally, we have demonstrated that pDCs, cDCs, and macrophages were required for generating IFN-α/β-induced subsequent protective immunity. Thus, our findings have identified a critical regulatory mechanism of type I IFN signaling in pDCs and stage-specific function of immune cells in generating potent immunity against lethal YM infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Shaping memory accuracy by left prefrontal transcranial direct current stimulation.

PubMed

Zwissler, Bastian; Sperber, Christoph; Aigeldinger, Sina; Schindler, Sebastian; Kissler, Johanna; Plewnia, Christian

2014-03-12

Human memory is dynamic and flexible but is also susceptible to distortions arising from adaptive as well as pathological processes. Both accurate and false memory formation require executive control that is critically mediated by the left prefrontal cortex (PFC). Transcranial direct current stimulation (tDCS) enables noninvasive modulation of cortical activity and associated behavior. The present study reports that tDCS applied to the left dorsolateral PFC (dlPFC) shaped accuracy of episodic memory via polaritiy-specific modulation of false recognition. When applied during encoding of pictures, anodal tDCS increased whereas cathodal stimulation reduced the number of false alarms to lure pictures in subsequent recognition memory testing. These data suggest that the enhancement of excitability in the dlPFC by anodal tDCS can be associated with blurred detail memory. In contrast, activity-reducing cathodal tDCS apparently acted as a noise filter inhibiting the development of imprecise memory traces and reducing the false memory rate. Consistently, the largest effect was found in the most active condition (i.e., for stimuli cued to be remembered). This first evidence for a polarity-specific, activity-dependent effect of tDCS on false memory opens new vistas for the understanding and potential treatment of disturbed memory control.

Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma.

PubMed

Tatsumi, T; Takehara, T; Kanto, T; Miyagi, T; Kuzushita, N; Sugimoto, Y; Jinushi, M; Kasahara, A; Sasaki, Y; Hori, M; Hayashi, N

2001-10-15

Dendritic cells (DCs) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combined effectiveness of tumor lysate-pulsed DC immunization and interleukin (IL)-12 administration on the induction of antitumor immunity in a mouse hepatocellular carcinoma (HCC) model. Mouse DCs were pulsed with lysate of BNL 1ME A.7R.1 (BNL), a BALB/c-derived HCC cell line, and then injected into syngeneic mice in combination with systemic administration of IL-12. Lymphocytes from mice treated with BNL lysate-pulsed DCs and IL-12 showed stronger cytolytic activity and produced higher amounts of IFN-gamma than those from mice treated with BNL lysate-pulsed DCs alone. Although immunization with BNL lysate-pulsed DCs alone did not lead to complete regression of established tumors, it significantly inhibited tumor growth compared with vehicle injection. Importantly, the combined therapy of BNL lysate-pulsed DCs and IL-12 resulted in tumor rejection or significant inhibition of tumor growth compared with mice treated with BNL lysate-pulsed DCs alone. In vivo lymphocyte depletion experiments demonstrated that this combination was dependent on both CD8+ and CD4+ T cells, but not natural killer cells. These results demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DCs against HCC in mice. This combination of IL-12 and DCs may be useful for suppressing the growth of residual tumor after primary therapy of human HCC.

Both anodal and cathodal transcranial direct current stimulation improves semantic processing.

PubMed

Brückner, Sabrina; Kammer, Thomas

2017-02-20

Transcranial direct current stimulation (tDCS) is a common method to modulate cortical activity. Anodal tDCS is usually associated with an enhancement of the stimulated brain area, whereas cathodal tDCS is often described as inhibitory brain stimulation method. Our aim was to investigate whether this canonical assumption derived from the motor system could be transferred to the semantic system. Three groups with 20 healthy subjects each were stimulated at Wernicke's area with either anodal, cathodal or sham tDCS. Subsequently, they performed a simple lexical decision task for a duration of about 25min. Subjects receiving anodal tDCS revealed faster reaction times (RTs) compared to the sham group, although not reaching statistical significance. Surprisingly, in the cathodal group RTs were decreased significantly. All subjects were faster in the second half of the task, but the tDCS-induced improvement lasted for the entire duration of the task. Error rates were not influenced by tDCS, neither were RTs in a choice reaction time task. Thus, both anodal and cathodal tDCS applied to Wernicke's area improved semantic processing. Recently, a meta-analysis revealed that the canonical anodal excitation and cathodal inhibition assumption is observed rarely in cognitive studies. In particular, an inhibitory effect of cathodal tDCS on cognition is rare. Our findings thus support the speculation, that especially language functions could be somewhat 'immune' to cathodal inhibition. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Molecular mechanisms of D-cycloserine in facilitating fear extinction: insights from RNAseq.

PubMed

Malan-Müller, Stefanie; Fairbairn, Lorren; Daniels, Willie M U; Dashti, Mahjoubeh Jalali Sefid; Oakeley, Edward J; Altorfer, Marc; Kidd, Martin; Seedat, Soraya; Gamieldien, Junaid; Hemmings, Sîan Megan Joanna

2016-02-01

D-cycloserine (DCS) has been shown to be effective in facilitating fear extinction in animal and human studies, however the precise mechanisms whereby the co-administration of DCS and behavioural fear extinction reduce fear are still unclear. This study investigated the molecular mechanisms of intrahippocampally administered D-cycloserine in facilitating fear extinction in a contextual fear conditioning animal model. Male Sprague Dawley rats (n = 120) were grouped into four experimental groups (n = 30) based on fear conditioning and intrahippocampal administration of either DCS or saline. The light/dark avoidance test was used to differentiate maladapted (MA) (anxious) from well-adapted (WA) (not anxious) subgroups. RNA extracted from the left dorsal hippocampus was used for RNA sequencing and gene expression data was compared between six fear-conditioned + saline MA (FEAR + SALINE MA) and six fear-conditioned + DCS WA (FEAR + DCS WA) animals. Of the 424 significantly downregulated and 25 significantly upregulated genes identified in the FEAR + DCS WA group compared to the FEAR + SALINE MA group, 121 downregulated and nine upregulated genes were predicted to be relevant to fear conditioning and anxiety and stress-related disorders. The majority of downregulated genes transcribed immune, proinflammatory and oxidative stress systems molecules. These molecules mediate neuroinflammation and cause neuronal damage. DCS also regulated genes involved in learning and memory processes, and genes associated with anxiety, stress-related disorders and co-occurring diseases (e.g., cardiovascular diseases, digestive system diseases and nervous system diseases). Identifying the molecular underpinnings of DCS-mediated fear extinction brings us closer to understanding the process of fear extinction.

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

PubMed

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.

EEG Driven tDCS Versus Bifrontal tDCS for Tinnitus

PubMed Central

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 tinnitus distress. The question arises whether optimization of the tDCS protocol can be obtained by using EEG driven decisions on where to place anode and cathode. Using gamma band functional connectivity could be superior to gamma band activity as functional connectivity determines the tinnitus network in many aspects of chronic tinnitus. Six-hundred-seventy-five patients were included in the study: 265 patients received tDCS with cathodal electrode placed over the left DLPFC and the anode placed overlying the right DLPFC, 380 patients received tDCS based on EEG connectivity, and 65 received no tDCS (i.e., waiting list control group). Repeated measures ANOVA revealed a significant main effect for pre versus post measurement. Bifrontal tDCS in comparison to EEG driven tDCS had a larger reduction for both tinnitus distress and tinnitus intensity. Whereas the results of the bifrontal tDCS seem to confirm previous studies, the use of gamma band functional connectivity seems not to bring any advantage to tDCS for tinnitus suppression. Using other potential biomarkers, such as gamma band activity, or theta functional connectivity could theoretically be of use. Further studies will have to elucidate whether brain state based tDCS has any advantages over “blind” bifrontal stimulation. PMID:23055986

Different effect of l-NAME treatment on susceptibility to decompression sickness in male and female rats.

PubMed

Mazur, Aleksandra; Buzzacott, Peter; Lambrechts, Kate; Wang, Qiong; Belhomme, Marc; Theron, Michael; Popov, Georgi; Distefano, Giovanni; Guerrero, Francois

2014-11-01

Vascular bubble formation results from supersaturation during inadequate decompression contributes to endothelial injuries, which form the basis for the development of decompression sickness (DCS). Risk factors for DCS include increased age, weight-fat mass, decreased maximal oxygen uptake, chronic diseases, dehydration, and nitric oxide (NO) bioavailability. Production of NO is often affected by diving and its expression-activity varies between the genders. Little is known about the influence of sex on the risk of DCS. To study this relationship we used an animal model of Nω-nitro-l-arginine methyl ester (l-NAME) to induce decreased NO production. Male and female rats with diverse ages and weights were divided into 2 groups: treated with l-NAME (in tap water; 0.05 mg·mL(-1) for 7 days) and a control group. To control the distribution of nitrogen among tissues, 2 different compression-decompression protocols were used. Results showed that l-NAME was significantly associated with increased DCS in female rats (p = 0.039) only. Weight was significant for both sexes (p = 0.01). The protocol with the highest estimated tissue pressures in the slower compartments was 2.6 times more likely to produce DCS than the protocol with the highest estimated tissue pressures in faster compartments. The outcome of this study had significantly different susceptibility to DCS after l-NAME treatment between the sexes, while l-NAME per se had no effect on the likelihood of DCS. The analysis also showed that for the appearance of DCS, the most significant factors were type of protocol and weight.

Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells

PubMed Central

Edelson, Brian T.; KC, Wumesh; Juang, Richard; Kohyama, Masako; Benoit, Loralyn A.; Klekotka, Paul A.; Moon, Clara; Albring, Jörn C.; Ise, Wataru; Michael, Drew G.; Bhattacharya, Deepta; Stappenbeck, Thaddeus S.; Holtzman, Michael J.; Sung, Sun-Sang J.; Murphy, Theresa L.; Hildner, Kai

2010-01-01

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3−/− mice also lack CD103+CD11b− DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3−/− mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b− DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3−/− mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ–resident CD8α+ cDCs and nonlymphoid CD103+ DCs. PMID:20351058

15 CFR 911.2 - Scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.2 Scope. (a) These regulations apply to any... data collection platforms to be used with the NOAA DCS either directly or through an affiliate or... Environmental Satellite (GOES) and Argos DCS users as well as all future applications for NOAA DCS use. ...

15 CFR 911.2 - Scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.2 Scope. (a) These regulations apply to any... data collection platforms to be used with the NOAA DCS either directly or through an affiliate or... Environmental Satellite (GOES) and Argos DCS users as well as all future applications for NOAA DCS use. ...

15 CFR 911.2 - Scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.2 Scope. (a) These regulations apply to any... data collection platforms to be used with the NOAA DCS either directly or through an affiliate or... Environmental Satellite (GOES) and Argos DCS users as well as all future applications for NOAA DCS use. ...

15 CFR 911.2 - Scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.2 Scope. (a) These regulations apply to any... data collection platforms to be used with the NOAA DCS either directly or through an affiliate or... Environmental Satellite (GOES) and Argos DCS users as well as all future applications for NOAA DCS use. ...

15 CFR 911.2 - Scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF THE NOAA SPACE-BASED DATA COLLECTION SYSTEMS § 911.2 Scope. (a) These regulations apply to any... data collection platforms to be used with the NOAA DCS either directly or through an affiliate or... Environmental Satellite (GOES) and Argos DCS users as well as all future applications for NOAA DCS use. ...

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

PubMed

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, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations. Copyright © 2015 Elsevier Inc. All rights reserved.

Systems biology of host-mycobiota interactions: dissecting Dectin-1 and Dectin-2 signalling in immune cells with DC-ATLAS.

PubMed

Rizzetto, Lisa; De Filippo, Carlotta; Rivero, Damariz; Riccadonna, Samantha; Beltrame, Luca; Cavalieri, Duccio

2013-11-01

Modelling the networks sustaining the fruitful coexistence between fungi and their mammalian hosts is becoming increasingly important to control emerging fungal pathogens. The C-type lectins Dectin-1 and Dectin-2 are involved in host defense mechanisms against fungal infection driving inflammatory and adaptive immune responses and complement in containing fungal burdens. Recognizing carbohydrate structures in pathogens, their engagement induces maturation of dendritic cells (DCs) into potent immuno-stimulatory cells endowed with the capacity to efficiently prime T cells. Owing to these properties, Dectin-1 and Dectin-2 agonists are currently under investigation as promising adjuvants in vaccination procedures for the treatment of fungal infection. Thus, a detailed understanding of events' cascade specifically triggered in DCs upon engagement is of great interest in translational research. Here, we summarize the current knowledge on Dectin-1 and Dectin-2 signalling in DCs highlighting similarities and differences. Detailed maps are annotated, using the Biological Connection Markup Language (BCML) data model, and stored in DC-ATLAS, a versatile resource for the interpretation of high-throughput data generated perturbing the signalling network of DCs. Copyright © 2013 Elsevier GmbH. All rights reserved.

Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia

PubMed Central

McConathey, Eric M.; White, Nicole C.; Gervits, Felix; Ash, Sherry; Coslett, H. Branch; Grossman, Murray; Hamilton, Roy H.

2017-01-01

Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities. Prior studies suggest that transcranial direct current stimulation (tDCS) directed toward language areas of the brain may help to ameliorate symptoms of PPA. In the present sham-controlled study, we examined whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with PPA variants primarily characterized by difficulties with speech production (non-fluent and logopenic). Participants were recruited from the Penn Frontotemporal Dementia Center to receive 10 days of both real and sham tDCS (counter-balanced, full-crossover design; participants were naïve to stimulation condition). A battery of language tests was administered at baseline, immediately post-tDCS (real and sham), and 6 weeks and 12 weeks following stimulation. When we accounted for individuals’ baseline performance, our analyses demonstrated a stratification of tDCS effects. Individuals who performed worse at baseline showed tDCS-related improvements in global language performance, grammatical comprehension and semantic processing. Individuals who performed better at baseline showed a slight tDCS-related benefit on our speech repetition metric. Real tDCS may improve language performance in some individuals with PPA. Severity of deficits at baseline may be an important factor in predicting which patients will respond positively to language-targeted tDCS therapies. Clinicaltrials.gov ID: NCT02928848 PMID:28713256

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps.

PubMed

Reckow, Jaclyn; Rahman-Filipiak, Annalise; Garcia, Sarah; Schlaefflin, Stephen; Calhoun, Oliver; DaSilva, Alexandre F; Bikson, Marom; Hampstead, Benjamin M

2018-05-04

Transcranial direct current stimulation (tDCS) is an in-demand form of neuromodulation generally regarded as safe and well tolerated. However, few studies have examined the safety, tolerability, or blinding of High Definition (HD-) tDCS, especially in older adults and at stimulation intensities of 2 milliamps (mA) or greater. We examined the rates of serious adverse events and common side effects to establish safety and tolerability, respectively, in HD-tDCS. Blinding was evaluated using participants' accuracy in correctly stating their condition (i.e., active or sham). The sample included 101 older adults (M age  = 69.69, SD = 8.33; M educ  = 16.27, SD = 2.42) who participated in our double blind randomized controlled studies or in case studies that used HD-tDCS for 20-30 min at 2 mA (n = 66, 31 active) or 3 mA (n = 35, 20 active). Participants completed a standardized side effect questionnaire and were asked whether they received active or sham stimulation at the end of each session. There were no serious adverse events and no participants withdrew, suggesting that HD-tDCS meets basic safety parameters. Tolerability was comparable between active and sham HD-tDCS regardless of intensity (2 mA and 3 mA) in first session (allp > .09). Tingling was the most commonly endorsed item (59% active; 56% sham) followed by burning sensation (51% active; 50% sham), the majority of which were mild in nature. "Severe" ratings were reported in fewer than 4% of sessions. Blinding appeared adequate since there were no significant group differences between individuals correctly stating their stimulation condition (χ2 = 0.689, p = .679). The above tolerability and blinding findings generally persisted when multiple session data (i.e., 186 total sessions) were considered. HD-tDCS appears well-tolerated and safe with effective sham-control in older adults, even at 3 mA. These data support the use of HD-tDCS in randomized controlled trials and clinical translation efforts. Published by Elsevier Inc.

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

PubMed

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 localisation of tDCS effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure.

PubMed

Li, Shan-Shan; Yang, Min; Chen, Yong-Ping; Tang, Xin-Yue; Zhang, Sheng-Guo; Ni, Shun-Lan; Yang, Nai-Bin; Lu, Ming-Qin

2018-05-28

Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d-galactosamine induced acute liver failure via inhibition of TLR4 pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia.

PubMed

Teichmann, Marc; Lesoil, Constance; Godard, Juliette; Vernet, Marine; Bertrand, Anne; Levy, Richard; Dubois, Bruno; Lemoine, Laurie; Truong, Dennis Q; Bikson, Marom; Kas, Aurélie; Valero-Cabré, Antoni

2016-11-01

Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small-cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv-PPA), applying a rigorous study design to a large, homogeneous sv-PPA cohort. Using a double-blind, sham-controlled counterbalanced cross-over design, we applied three tDCS conditions targeting the temporal poles of 12 sv-PPA patients. Efficiency was assessed by a semantic matching task orthogonally manipulating "living"/"nonliving" categories and verbal/visual modalities. Conforming to predominantly left-lateralized damage in sv-PPA and accounts of interhemispheric inhibition, we applied left hemisphere anodal-excitatory and right hemisphere cathodal-inhibitory tDCS, compared to sham stimulation. Prestimulation data, compared to 15 healthy controls, showed that patients had semantic disorders predominating with living categories in the verbal modality. Stimulation selectively impacted these most impaired domains: Left-excitatory and right-inhibitory tDCS improved semantic accuracy in verbal modality, and right-inhibitory tDCS improved processing speed with living categories and accuracy and processing speed in the combined verbal × living condition. Our findings demonstrate the efficiency of tDCS in sv-PPA by generating highly specific intrasemantic effects. They provide "proof of concept" for future applications of tDCS in therapeutic multiday regimes, potentially driving sustained improvement of semantic processing. Our data also support the hotly debated existence of a left temporal-pole network for verbal semantics selectively modulated through both left-excitatory and right-inhibitory brain stimulation. Ann Neurol 2016;80:693-707. © 2016 American Neurological Association.

The use of LANDSAT DCS and imagery in reservoir management and operation

NASA Technical Reports Server (NTRS)

Cooper, S.; Bock, P.; Horowitz, J.; Foran, D.

1975-01-01

Experiments by the New England Division (NED), Corps of Engineers with LANDSAT-1 data collection and imaging systems are reported. Data cover the future usefulness of data products received from satellites such as LANDSAT in the day to day operation of NED water resources systems used to control floods.

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

PubMed Central

Vallée, Nicolas; Ignatescu, Mihaela; Bourdon, Lionel

2011-01-01

Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats (n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg−1·day−1, n = 30), Clo (50 mg·kg−1·day−1, n = 60), Hep (500 IU/kg, n = 30), or to untreated group (n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA (n = 13), Clo (n = 13), or Hep (n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (−4,5% with Clo, −19.5% with ASA, −19,9% with Hep, and −29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin generation, have no protective effect on DCS incidence. Clo, a specific ADP-receptor antagonist, reduces post-decompression platelet consumption. These results point to the predominant involvement of the ADP release in BIPA but cannot differentiate definitively between bubble-induced vessel wall injury and bubble-blood component interactions in DCS. PMID:21212250

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.

PubMed

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. The study investigates whether CBT can be augmented by non-invasive brain stimulation techniques such as tDCS in the treatment of MDD. It is designed as a proof-of-principle trial for the combined tDCS-CBT treatment, but also allows the investigation of the neurobiological underpinnings of the interaction between both interventions in MDD. Trial registration ClinicalTrials.gov Identifier NCT02633449.

The Effect of Environmental Conditions on Tropical Deep Convective Systems Observed from the TRMM Satellite

NASA Technical Reports Server (NTRS)

Lin, Bing; Wielicki, Bruce A.; Minnis, Patrick; Chambers, Lin H.; Xu, Kuan-Man; Hu, Yongxiang; Fan, Tai-Fang

2005-01-01

This study uses measurements of radiation and cloud properties taken between January and August 1998 by three Tropical Rainfall Measuring Mission (TRMM) instruments, the Clouds and the Earth's Radiant Energy System (CERES) scanner, the TRMM Microwave Imager (TMI), and the Visible and InfraRed Scanner (VIRS), to evaluate the variations of tropical deep convective systems (DCS) with sea surface temperature (SST) and precipitation. This study finds that DCS precipitation efficiency increases with SST at a rate of approx. 2%/K. Despite increasing rainfall efficiency, the cloud areal coverage rises with SST at a rate of about 7%/K in the warm tropical seas. There, the boundary layer moisture supply for deep convection and the moisture transported to the upper troposphere for cirrus-anvil cloud formation increase by approx. 6.3%/K and approx. 4.0%/K, respectively. The changes in cloud formation efficiency, along with the increased transport of moisture available for cloud formation, likely contribute to the large rate of increasing DCS areal coverage. Although no direct observations are available, the increase of cloud formation efficiency with rising SST is deduced indirectly from measurements of changes in the ratio of DCS ice water path and boundary layer water vapor amount with SST. Besides the cloud areal coverage, DCS cluster effective sizes also increase with precipitation. Furthermore, other cloud properties, such as cloud total water and ice water paths, increase with SST. These changes in DCS properties will produce a negative radiative feedback for the earth's climate system due to strong reflection of shortwave radiation by the DCS. These results significantly differ from some previous hypothesized dehydration scenarios for warmer climates, and have great potential in testing current cloud-system resolving models and convective parameterizations of general circulation models.

Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia

PubMed Central

Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi; Rosa Fortuno, C; Fenoglio, Angela; Roche-Labarbe, Nadège; Soul, Janet S; Franceschini, Maria Angela; Grant, P Ellen

2014-01-01

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS–DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS–DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization. PMID:24064492

Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: randomized controlled preliminary study.

PubMed

Gillick, Bernadette T; Feyma, Tim; Menk, Jeremiah; Usset, Michelle; Vaith, Amy; Wood, Teddi Jean; Worthington, Rebecca; Krach, Linda E

2015-03-01

Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. The study was conducted in a university pediatric research laboratory. Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Adverse events/safety assessment and hand function were measured. Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. A limitation of the study was the small sample size, with data available for 11 participants. Based on the results of this study, tDCS appears to be safe, feasible, and well tolerated in most children with hemiparesis. Future investigations of serial sessions of tDCS in conjunction with rehabilitation in pediatric hemiparesis are indicated to explore the benefit of a synergistic approach to improving hand function. © 2015 American Physical Therapy Association.

Safety and Feasibility of Transcranial Direct Current Stimulation in Pediatric Hemiparesis: Randomized Controlled Preliminary Study

PubMed Central

Feyma, Tim; Menk, Jeremiah; Usset, Michelle; Vaith, Amy; Wood, Teddi Jean; Worthington, Rebecca; Krach, Linda E.

2015-01-01

Background Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. Objective The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. Design A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. Setting The study was conducted in a university pediatric research laboratory. Participants Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Measurements Adverse events/safety assessment and hand function were measured. Intervention Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. Results No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. Limitations A limitation of the study was the small sample size, with data available for 11 participants. Conclusions Based on the results of this study, tDCS appears to be safe, feasible, and well tolerated in most children with hemiparesis. Future investigations of serial sessions of tDCS in conjunction with rehabilitation in pediatric hemiparesis are indicated to explore the benefit of a synergistic approach to improving hand function. PMID:25413621

The effect of transcranial direct current stimulation of the prefrontal cortex on implicit self-esteem is mediated by rumination after criticism.

PubMed

De Raedt, Rudi; Remue, Jonathan; Loeys, Tom; Hooley, Jill M; Baeken, Chris

2017-12-01

It has been proposed that a crucial link between cognitive (i.e., self-schemas) and biological vulnerability is prefrontal control. This is because decreased control leads to impaired ability to inhibit ruminative thinking after the activation of negative self-schemas. However, current evidence is mainly correlational. In the current experimental study we tested whether the effect of neurostimulation of the dorsolateral prefrontal cortex (DLPFC) on self-esteem is mediated by momentary ruminative self-referential thinking (MRST) after the induction of negative self-schemas by criticism. We used a single, sham-controlled crossover session of anodal transcranial Direct Current Stimulation (tDCS) applied to the left DLPFC (cathode over the right supraorbital region) in healthy female individuals. After receiving tDCS/sham stimulation, we measured MRST and exposed the participants to critical audio scripts, followed by another MRST measurement. Subsequently, all participants completed two Implicit Relational Assessment Procedures to implicitly measure actual and ideal self-esteem. Our behavioral data indicated a significant decrease in MRST after real but not sham tDCS. Moreover, although there was no immediate effect of tDCS on implicit self-esteem, an indirect effect was found through double mediation, with the difference in MRST from baseline to after stimulation and from baseline to after criticism as our two mediators. The larger the decrease of criticism induced MRST after real tDCS, the higher the level of actual self-esteem. Our results show that tDCS can influence cognitive processes such as rumination, and subsequently self-esteem, but only after the activation of negative self-schemas. Rumination and negative self-esteem characterize different forms of psychopathology, and these data expand our knowledge of the role of the prefrontal cortex in controlling these self-referential processes, and the mechanisms of action of tDCS. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis

PubMed Central

Cruzat, Andrea; Witkin, Deborah; Baniasadi, Neda; Zheng, Lixin; Ciolino, Joseph B.; Jurkunas, Ula V.; Chodosh, James; Pavan-Langston, Deborah; Dana, Reza

2011-01-01

Purpose. To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). Methods. IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the “in vivo” nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. Results. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm2; P < 0.0001), fungal (608.9 ± 812.5 cells/mm2; P < 0.0001), and Acanthamoeba keratitis (1000.2 ± 1090.3 cells/mm2; P < 0.0001) compared with controls (49.3 ± 39.6 cells/mm2). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 ± 976.1 vs. 3913.9 ± 507.4 μm/frame), total nerve numbers (2.7 ± 3.9 vs. 20.2 ± 3.3), main trunks (1.5 ± 2.2 vs. 6.9 ± 1.1), and branching (1.2 ± 2.0 vs. 13.5 ± 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r = −0.44; P < 0.0005). Conclusions. IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea. PMID:21460259

Influenza A Virus Infection of Human Primary Dendritic Cells Impairs Their Ability to Cross-Present Antigen to CD8 T Cells

PubMed Central

Smed-Sörensen, Anna; Chalouni, Cécile; Chatterjee, Bithi; Cohn, Lillian; Blattmann, Peter; Nakamura, Norihiro; Delamarre, Lélia; Mellman, Ira

2012-01-01

Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated by dendritic cells (DCs). We investigated the consequences of IAV infection of human primary DCs on their ability to function as antigen-presenting cells. IAV was internalized by both myeloid DCs (mDCs) and plasmacytoid DCs but only mDCs supported viral replication. Although infected mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not the case for presentation on MHC class I. Indeed, cross-presentation by uninfected cells of minute amounts of endocytosed, exogenous IAV was ∼300-fold more efficient than presentation of IAV antigens synthesized by infected cells and resulted in a statistically significant increase in expansion of IAV-specific CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other exogenous antigens, indicating that IAV infection broadly attenuates presentation on MHC class I molecules. Our results suggest that cross-presentation by uninfected mDCs is a preferred mechanism of antigen-presentation for the activation and expansion of CD8 T cells during IAV infection. PMID:22412374

Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition

PubMed Central

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

Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC).

PubMed

Salehinejad, Mohammad Ali; Ghanavai, Elham; Rostami, Reza; Nejati, Vahid

2017-03-01

Previous studies showed that MD is associated with a variety of cognitive deficits and executive dysfunctions which can persist even in remitted states. However, the role of cognitive impairments in MD psychopathology and treatment is not fully understood. This article aims to discuss how executive functions central components (e.g., Working memory and attention) mediate MD psychopathology considering the role of dorsolateral prefrontal cortex (dLPFC) and present findings of a brain stimulation experiment to support this notion. The effect of transcranial direct current stimulation (tDCS) of the dLPFC on enhancing cognitive control functions was investigated. Twenty-four patients with MD (Experimental group=12, Control group=12) received 10 sessions of tDCS (2mA for 30min) over 10 consecutive days. The experimental group received active stimulation and the control group received sham stimulation. Participant's performance on cognitive functions (PAL, SRM, RVP and CRT from CANTAB) and their depression scores were assessed before and after tDCS. Results showed that brain stimulation of the dLPFC improved executive dysfunction in patients and a significant improvement on depression scores was also observed suggesting that cognitive control dysfunction may be a mediator in emotional dysregulation and psychopathology of MD. No follow-up investigation was done in this study which does not allow to infer long-term effect of tDCS. Low-focality of tDCS might have stimulated adjacent areas too. Cognitive components, namely cognitive control dysfunction, play role in MD psychopathology as they are involved in emotion dysregulation in MD. The amount of contribution of cognitive components in MD psychopathology is however, an open question. tDCS can be used as an intervention to improve cognitive dysfunction in MD. Copyright © 2017 Elsevier B.V. All rights reserved.

d-Cycloserine enhances durability of social skills training in autism spectrum disorder.

PubMed

Wink, Logan K; Minshawi, Noha F; Shaffer, Rebecca C; Plawecki, Martin H; Posey, David J; Horn, Paul S; Adams, Ryan; Pedapati, Ernest V; Schaefer, Tori L; McDougle, Christopher J; Swiezy, Naomi B; Erickson, Craig A

2017-01-01

d-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability. Study participants included 60 outpatient youth with ASD, ages 5-11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22. Analysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group ( p  = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups. The findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training. ClinicalTrials.gov, NCT01086475.

Dendritic cells from CML patients have altered actin organization, reduced antigen processing, and impaired migration.

PubMed

Dong, Rong; Cwynarski, Kate; Entwistle, Alan; Marelli-Berg, Federica; Dazzi, Francesco; Simpson, Elizabeth; Goldman, John M; Melo, Junia V; Lechler, Robert I; Bellantuono, Ilaria; Ridley, Anne; Lombardi, Giovanna

2003-05-01

Chronic myeloid leukemia (CML) is characterized by expression of the BCR-ABL fusion gene that encodes a 210-kDa protein, which is a constitutively active tyrosine kinase. At least 70% of the oncoprotein is localized to the cytoskeleton, and several of the most prominent tyrosine kinase substrates for p210(BCR-ABL) are cytoskeletal proteins. Dendritic cells (DCs) are bone marrow-derived antigen-presenting cells responsible for the initiation of immune responses. In CML patients, up to 98% of myeloid DCs generated from peripheral blood mononuclear cells are BCR-ABL positive. In this study we have compared the morphology and behavior of myeloid DCs derived from CML patients with control DCs from healthy individuals. We show that the actin cytoskeleton and shape of CML-DCs of myeloid origin adherent to fibronectin differ significantly from those of normal DCs. CML-DCs are also defective in processing and presentation of exogenous antigens such as tetanus toxoid. The antigen-processing defect may be a consequence of the reduced capacity of CML-DCs to capture antigen via macropinocytosis or via mannose receptors when compared with DCs generated from healthy individuals. Furthermore, chemokine-induced migration of CML-DCs in vitro was significantly reduced. These observations cannot be explained by a difference in the maturation status of CML and normal DCs, because phenotypic analysis by flow cytometry showed a similar surface expression of maturation makers. Taken together, these results suggest that the defects in antigen processing and migration we have observed in CML-DCs may be related to underlying cytoskeletal changes induced by the p210(BCR-ABL) fusion protein.

[Application of damage control surgery idea in the treatment of severe pancreatic duodenal injury].

PubMed

Zhu, Ren-wu; Gu, Ye-chun; Jiang, Yang-gui; Zhao, Mao-sen; Shen, Xian

2013-12-01

To explore the significance of damage control surgery (DCS) in the treatments of severe pancreaticoduodenal injuries. Clinical data of 19 patients with severe pancreaticoduodenal injuries managed with DCS approach in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine and the First Affiliated Hospital of Wenzhou Medical College from March 2005 to January 2013 were analyzed retrospectively. Three cases were cured after damage control operation and postoperative ICU resuscitation treatment. Twelve cases underwent definite operations (distal pancreaticojejunal Roux-en-Y anastomosis, proximal duodenojejunal Roux-en-Y anastomosis or pancreaticoduodenectomy) after damage control operation and postoperative ICU resuscitation treatment and cured. Four cases died after damage control operation due to multiple organ failure and the mortality was 21.1%. Application of DCS approach can improve the prognosis of patients with severe pancreaticoduodenal injuries.

Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection.

PubMed

Blasius, Amanda L; Krebs, Philippe; Sullivan, Brian M; Oldstone, Michael B; Popkin, Daniel L

2012-09-01

Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.

Dendritic cells coordinate innate immunity via MyD88 signaling to control Listeria monocytogenes infection.

PubMed

Arnold-Schrauf, Catharina; Dudek, Markus; Dielmann, Anastasia; Pace, Luigia; Swallow, Maxine; Kruse, Friederike; Kühl, Anja A; Holzmann, Bernhard; Berod, Luciana; Sparwasser, Tim

2014-02-27

Listeria monocytogenes (LM), a facultative intracellular Gram-positive pathogen, can cause life-threatening infections in humans. In mice, the signaling cascade downstream of the myeloid differentiation factor 88 (MyD88) is essential for proper innate immune activation against LM, as MyD88-deficient mice succumb early to infection. Here, we show that MyD88 signaling in dendritic cells (DCs) is sufficient to mediate the protective innate response, including the production of proinflammatory cytokines, neutrophil infiltration, bacterial clearance, and full protection from lethal infection. We also demonstrate that MyD88 signaling by DCs controls the infection rates of CD8α(+) cDCs and thus limits the spread of LM to the T cell areas. Furthermore, in mice expressing MyD88 in DCs, inflammatory monocytes, which are required for bacterial clearance, are activated independently of intrinsic MyD88 signaling. In conclusion, CD11c(+) conventional DCs critically integrate pathogen-derived signals via MyD88 signaling during early infection with LM in vivo. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults.

PubMed

Prehn, Kristin; Stengl, Helena; Grittner, Ulrike; Kosiolek, René; Ölschläger, Anja; Weidemann, Alexandra; Flöel, Agnes

2017-01-01

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation.

Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults

PubMed Central

Prehn, Kristin; Stengl, Helena; Grittner, Ulrike; Kosiolek, René; Ölschläger, Anja; Weidemann, Alexandra; Flöel, Agnes

2017-01-01

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation. PMID:27555381

Decompression Sickness After Air Break in Prebreathe Described with a Survival Model

NASA Technical Reports Server (NTRS)

Conkin, J.; Pilmanis, A. A.

2010-01-01

Data from Brooks City-Base show the decompression sickness (DCS) and venous gas emboli (VGE) consequences of air breaks in a resting 100% O2 prebreathe (PB) prior to a hypobaric exposure. METHODS: DCS and VGE survival times from 95 controls for a 60 min PB prior to 2-hr or 4-hr exposures to 4.37 psia are statistically compared to 3 break in PB conditions: a 10 min (n=40), 20 min (n=40), or 60 min break (n=32) 30 min into the PB followed by 30 min of PB. Ascent rate was 1,524 meters / min and all exposures included light exercise and 4 min of VGE monitoring of heart chambers at 16 min intervals. DCS survival time for combined control and air breaks were described with an accelerated log logistic model where exponential N2 washin during air break was described with a 10 min half-time and washout during PB with a 60 min half-time. RESULTS: There was no difference in VGE or DCS survival times among 3 different air breaks, or when air breaks were compared to control VGE times. However, 10, 20, and 60 min air breaks had significantly earlier survival times compared to control DCS times, certainly early in the exposures. CONCLUSION: Air breaks of 10, 20, and 60 min after 30 min of a 60 min PB reduced DCS survival time. The survival model combined discrete comparisons into a global description mechanistically linked to asymmetrical N2 washin and washout kinetics based on inspired pN2. Our unvalidated regression is used to compute additional PB time needed to compensate for an air break in PB within the range of tested conditions.

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Cosmo, Camila; Baptista, Abrahão Fontes; de Araújo, Arão Nogueira; do Rosário, Raphael Silva; Miranda, José Garcia Vivas; Montoya, Pedro; de Sena, Eduardo Pondé

2015-01-01

Background Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD) have not yet been investigated. Methods A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation. Results A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures—correct responses, impulsivity and omission errors—were small. No adverse events resulting from stimulation were reported. Conclusion According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population. Trial Registration ClinicalTrials.gov NCT01968512 PMID:26267861

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder.

PubMed

Cosmo, Camila; Baptista, Abrahão Fontes; de Araújo, Arão Nogueira; do Rosário, Raphael Silva; Miranda, José Garcia Vivas; Montoya, Pedro; de Sena, Eduardo Pondé

2015-01-01

Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD) have not yet been investigated. A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation. A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures-correct responses, impulsivity and omission errors--were small. No adverse events resulting from stimulation were reported. According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population. ClinicalTrials.gov NCT01968512.

Are Locking Constructs in Distal Femoral Fractures Always Best? A Prospective Multicenter Randomized Controlled Trial Comparing the Less Invasive Stabilization System With the Minimally Invasive Dynamic Condylar Screw System.

PubMed

2016-01-01

The purpose of this clinical study is to determine whether the rate of fracture healing and fracture union, repaired with a locked device, will be as good as or better than standard nonlocking bicortical fixation in distal femoral fractures. Institutional review board-approved, multicenter prospective randomized controlled trial. Seven level 1 trauma centers across Canada. Fifty-two patients with distal femoral fractures (AO/OTA 33A1 to 33C2) were enrolled in the randomized trial. Twelve AO/OTA 33C3 fractures were excluded from the randomized trial but followed up as a nonrandomized cohort. Patients were treated through a standardized minimally invasive approach. Fractures were randomized 1:1 to treatment with the locked Less Invasive Stabilization System (LISS; Synthes, Paoli, PA) or the dynamic condylar screw (DCS). The nonrandomized cohort was treated at the surgeon's discretion. Primary outcomes were time to radiological union and number of delayed/nonunions at 12 months. Secondary outcomes were postoperative function and complications. Fifty-two patients were randomized including 34 women and 18 men. The mean age was 59 years. Twenty-eight patients were treated with the LISS and 24 with the DCS. There was no statistically significant difference between the LISS and the DCS in terms of the number of fractures healed, time to union, or functional scores. Complications and revisions were more common in the LISS group. There were 7 reoperations in the LISS group and one in the DCS group. Only 52% of the LISS group healed without intervention by 12 months compared with 91% in the DCS group. There was no advantage to the locking plate design in the management of distal femoral fractures in this study. The higher cost of the locking plates, challenges in technique, and lack of superiority have led the authors to discontinue the use of this lateral unicortical locking device in favor of other devices that allow locked or nonlocked bicortical fixation, articular compression, and bridging of the comminuted fracture segments. The cost-effective treatment for a subgroup or periarticular fractures may be a fixed-angle nonlocked device in patients with reasonable bone quality. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

PubMed

Alaoui, Lamine; Palomino, Gustavo; Zurawski, Sandy; Zurawski, Gerard; Coindre, Sixtine; Dereuddre-Bosquet, Nathalie; Lecuroux, Camille; Goujard, Cecile; Vaslin, Bruno; Bourgeois, Christine; Roques, Pierre; Le Grand, Roger; Lambotte, Olivier; Favier, Benoit

2018-05-01

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.

Effects of transcranial direct current stimulation on the auditory mismatch negativity response and working memory performance in schizophrenia: a pilot study.

PubMed

Impey, Danielle; Baddeley, Ashley; Nelson, Renee; Labelle, Alain; Knott, Verner

2017-11-01

Cognitive impairment has been proposed to be the core feature of schizophrenia (Sz). Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which can improve cognitive function in healthy participants and in psychiatric patients with cognitive deficits. tDCS has been shown to improve cognition and hallucination symptoms in Sz, a disorder also associated with marked sensory processing deficits. Recent findings in healthy controls demonstrate that anodal tDCS increases auditory deviance detection, as measured by the brain-based event-related potential, mismatch negativity (MMN), which is a putative biomarker of Sz that has been proposed as a target for treatment of Sz cognition. This pilot study conducted a randomized, double-blind assessment of the effects of pre- and post-tDCS on MMN-indexed auditory discrimination in 12 Sz patients, moderated by auditory hallucination (AH) presence, as well as working memory performance. Assessments were conducted in three sessions involving temporal and frontal lobe anodal stimulation (to transiently excite local brain activity), and one control session involving 'sham' stimulation (meaning with the device turned off, i.e., no stimulation). Results demonstrated a trend for pitch MMN amplitude to increase with anodal temporal tDCS, which was significant in a subgroup of Sz individuals with AHs. Anodal frontal tDCS significantly increased WM performance on the 2-back task, which was found to positively correlate with MMN-tDCS effects. The findings contribute to our understanding of tDCS effects for sensory processing deficits and working memory performance in Sz and may have implications for psychiatric disorders with sensory deficits.

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

PubMed

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.

Enhanced Induction of T Cell Immunity Using Dendritic Cells Pulsed with HIV Tat and HCMV-pp65 Fusion Protein In Vitro

PubMed Central

Park, Jung-Sun; Park, Soo-Young; Cho, Hyun-Il; Sohn, Hyun-Jung

2011-01-01

Background Cytotoxic T lymphocytes (CTLs) appear to play an important role in the control and prevention of human cytomegalovirus (HCMV) infection. The pp65 antigen is a structural protein, which has been defined as a potential target for effective immunity against HCMV infection. Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (Tat) into protein facilitates rapid, efficient entry into cells. Methods To establish a strategy for the generation of HCMV-specific CTLs in vitro, recombinant truncated N- and C-terminal pp65 protein (pp65 N&C) and N- and C-terminal pp65 protein fused with Tat (Tat/pp65 N&C) was produced in E.coli system. Peripheral blood mononuclear cells were stimulated with dendritic cells (DCs) pulsed with pp65 N&C or Tat/pp65 N&C protein and immune responses induced was examined using IFN-γ ELISPOT assay, cytotoxicity assay and tetramer staining. Results DCs pulsed with Tat/pp65N&C protein could induce higher T-cell responses in vitro compared with pp65N&C. Moreover, the DCs pulsed with Tat/pp65 N&C could stimulate both of CD8+ and CD4+ T-cell responses. The T cells induced by DCs pulsed with Tat/pp65 N&C showed higher cytotoxicity than that of pp65-pulsed DCs against autologous lymphoblastoid B-cell line (LCL) expressing the HCMV-pp65 antigen. Conclusion Our results suggest that DCs pulsed with Tat/pp65 N&C protein effectively induced pp65-specific CTL in vitro. Tat fusion recombinant protein may be useful for the development of adoptive T-cell immunotherapy and DC-based vaccines. PMID:21860612

Invariant natural killer T-cell control of type 1 diabetes: a dendritic cell genetic decision of a silver bullet or Russian roulette.

PubMed

Driver, John P; Scheuplein, Felix; Chen, Yi-Guang; Grier, Alexandra E; Wilson, S Brian; Serreze, David V

2010-02-01

In part, activation of invariant natural killer T (iNKT)-cells with the superagonist alpha-galactosylceramide (alpha-GalCer) inhibits the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotolerogenic state. However, in other systems iNKT-cell activation has an adjuvant-like effect that enhances rather than suppresses various immunological responses. Thus, we tested whether in some circumstances genetic variation would enable activated iNKT-cells to support rather than inhibit type 1 diabetes development. We tested whether iNKT-conditioned DCs in NOD mice and a major histocompatibility complex-matched C57BL/6 (B6) background congenic stock differed in capacity to inhibit type 1 diabetes induced by the adoptive transfer of pathogenic AI4 CD8 T-cells. Unlike those of NOD origin, iNKT-conditioned DCs in the B6 background stock matured to a state that actually supported rather than inhibited AI4 T-cell-induced type 1 diabetes. The induction of a differing activity pattern of T-cell costimulatory molecules varying in capacity to override programmed death-ligand-1 inhibitory effects contributes to the respective ability of iNKT-conditioned DCs in NOD and B6 background mice to inhibit or support type 1 diabetes development. Genetic differences inherent to both iNKT-cells and DCs contribute to their varying interactions in NOD and B6.H2(g7) mice. This great variability in the interactions between iNKT-cells and DCs in two inbred mouse strains should raise a cautionary note about considering manipulation of this axis as a potential type 1 diabetes prevention therapy in genetically heterogeneous humans.

Adapting Dry Cask Storage for Aging at a Geologic Repository

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

C. Sanders; D. Kimball

2005-08-02

A Spent Nuclear Fuel (SNF) Aging System is a crucial part of operations at the proposed Yucca Mountain repository in the United States. Incoming commercial SNF that does not meet thermal limits for emplacement will be aged on outdoor pads. U.S. Department of Energy SNF will also be managed using the Aging System. Proposed site-specific designs for the Aging System are closely based upon designs for existing dry cask storage (DCS) systems. This paper evaluates the applicability of existing DCS systems for use in the SNF Aging System at Yucca Mountain. The most important difference between existing DCS facilities andmore » the Yucca Mountain facility is the required capacity. Existing DCS facilities typically have less than 50 casks. The current design for the aging pad at Yucca Mountain calls for a capacity of over 2,000 casks (20,000 MTHM) [1]. This unprecedented number of casks poses some unique problems. The response of DCS systems to off-normal and accident conditions needs to be re-evaluated for multiple storage casks. Dose calculations become more complicated, since doses from multiple or very long arrays of casks can dramatically increase the total boundary dose. For occupational doses, the geometry of the cask arrays and the order of loading casks must be carefully considered in order to meet ALARA goals during cask retrieval. Due to the large area of the aging pad, skyshine must also be included when calculating public and worker doses. The expected length of aging will also necessitate some design adjustments. Under 10 CFR 72.236, DCS systems are initially certified for a period of 20 years [2]. Although the Yucca Mountain facility is not intended to be a storage facility under 10 CFR 72, the operational life of the SNF Aging System is 50 years [1]. Any cask system selected for use in aging will have to be qualified to this design lifetime. These considerations are examined, and a summary is provided of the adaptations that must be made in order to use DCS technologies successfully at a geologic repository.« less

The varieties of immunological experience: of pathogens, stress, and dendritic cells.

PubMed

Pulendran, Bali

2015-01-01

In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.

Human dendritic cells in the severe combined immunodeficiency mouse model: their potentiating role in the allergic reaction.

PubMed

Hammad, H; Duez, C; Fahy, O; Tsicopoulos, A; André, C; Wallaert, B; Lebecque, S; Tonnel, A B; Pestel, J

2000-04-01

Dendritic cells (DCs) are present in the lungs and airways of healthy and allergic subjects where they are exposed to inhaled antigens. After the uptake of antigens, DCs migrate to lymphoid organs where T cells initiate and control the immune response. The migratory properties of DCs are an essential component of their function but remain unclear in the situation of allergic diseases. To better understand the role of DCs in response to allergens, we first investigated their presence in an original experimental model of allergic asthma: the humanized severe combined immunodeficiency (SCID) mouse reconstituted with peripheral blood mononuclear cells from patients sensitive to Dermatophagoides pteronyssinus (Dpt). Human DCs were detected in lungs of mice developing an inflammatory pulmonary infiltrate and appeared to be mainly located in the alveolar spaces. In a second step, human DCs were generated in vitro from monocytes and injected into naive SCID mice exposed or not exposed to Dpt aerosols. Their migratory behavior was explored, as well as their potential role in modulating the IgE production after exposure to Dpt. After exposure to Dpt, the number of DCs present in airways decreased, while it increased into the spleen and thymus of the mice. The IgE production increased in the presence of DCs as compared with mice not injected with DCs. These results suggest that DCs may play a role in the pulmonary allergic reaction developed in response to Dpt in SCID mice.

Cyber security risk assessment for SCADA and DCS networks.

PubMed

Ralston, P A S; Graham, J H; Hieb, J L

2007-10-01

The growing dependence of critical infrastructures and industrial automation on interconnected physical and cyber-based control systems has resulted in a growing and previously unforeseen cyber security threat to supervisory control and data acquisition (SCADA) and distributed control systems (DCSs). It is critical that engineers and managers understand these issues and know how to locate the information they need. This paper provides a broad overview of cyber security and risk assessment for SCADA and DCS, introduces the main industry organizations and government groups working in this area, and gives a comprehensive review of the literature to date. Major concepts related to the risk assessment methods are introduced with references cited for more detail. Included are risk assessment methods such as HHM, IIM, and RFRM which have been applied successfully to SCADA systems with many interdependencies and have highlighted the need for quantifiable metrics. Presented in broad terms is probability risk analysis (PRA) which includes methods such as FTA, ETA, and FEMA. The paper concludes with a general discussion of two recent methods (one based on compromise graphs and one on augmented vulnerability trees) that quantitatively determine the probability of an attack, the impact of the attack, and the reduction in risk associated with a particular countermeasure.

Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

PubMed Central

Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

2014-01-01

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine.

PubMed

Jahan, Sheikh Tasnim; Sadat, Sams Ma; Haddadi, Azita

2018-01-01

The aim of this research was to develop a targeted antigen-adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method. Targeted NPs were obtained through ligand incorporation via physical adsorption or chemical conjugation process. Intracellular uptake of the NPs and the maturation of DCs were evaluated with flow cytometry. Remarkably, the developed delivery system had suitable physicochemical properties, such as particle size, surface charge, OV encapsulation efficiency, biphasic OV release pattern, and safety profile. The ligand modified formulations had higher targeting efficiency than the non-tailored NPs. This was also evident when the targeted formulations expressed comparatively higher fold increase in surface activation markers such as CD40, CD86, and major histocompatibility complex class II molecules. The maturation of DCs was further confirmed through secretion of extracellular cytokines compared to control cells in the DC microenvironment. Physicochemical characterization of NPs was performed based on the polymer end groups, their viscosities, and ligand-NP bonding type. In conclusion, the DC stimulatory response was integrated to develop a relationship between the NP structure and desired immune response. Therefore, the present study narrates a comparative evaluation of some selected parameters to choose a suitable formulation useful for in vivo cancer immunotherapy.

Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

PubMed

Kantak, Shailesh S; Mummidisetty, Chaithanya K; Stinear, James W

2012-09-01

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human

PubMed Central

Fonteneau, Clara; Redoute, Jérome; Haesebaert, Frédéric; Le Bars, Didier; Costes, Nicolas; Suaud-Chagny, Marie-Françoise; Brunelin, Jérome

2018-01-01

Abstract A single transcranial direct current stimulation (tDCS) session applied over the dorsolateral prefrontal cortex (DLFPC) can be associated with procognitive effects. Furthermore, repeated DLPFC tDCS sessions are under investigation as a new therapeutic tool for a range of neuropsychiatric conditions. A possible mechanism explaining such beneficial effects is a modulation of meso-cortico-limbic dopamine transmission. We explored the spatial and temporal neurobiological effects of bifrontal tDCS on subcortical dopamine transmission during and immediately after the stimulation. In a double blind sham-controlled study, 32 healthy subjects randomly received a single session of either active (20 min, 2 mA; n = 14) or sham (n = 18) tDCS during a dynamic positron emission tomography scan using [11C]raclopride binding. During the stimulation period, no significant effect of tDCS was observed. After the stimulation period, compared with sham tDCS, active tDCS induced a significant decrease in [11C]raclopride binding potential ratio in the striatum, suggesting an increase in extracellular dopamine in a part of the striatum involved in the reward–motivation network. The present study provides the first evidence that bifrontal tDCS induces neurotransmitter release in polysynaptic connected subcortical areas. Therefore, levels of dopamine activity and reactivity should be a new element to consider for a general hypothesis of brain modulation by bifrontal tDCS. PMID:29688276

Transcranial direct current stimulation to primary motor area improves hand dexterity and selective attention in chronic stroke.

PubMed

Au-Yeung, Stephanie S Y; Wang, Juliana; Chen, Ye; Chua, Eldrich

2014-12-01

The aim of this study was to determine whether transcranial direct current stimulation (tDCS) applied to the primary motor hand area modulates hand dexterity and selective attention after stroke. This study was a double-blind, placebo-controlled, randomized crossover trial involving subjects with chronic stroke. Ten stroke survivors with some pinch strength in the paretic hand received three different tDCS interventions assigned in random order in separate sessions-anodal tDCS targeting the primary motor area of the lesioned hemisphere (M1lesioned), cathodal tDCS applied to the contralateral hemisphere (M1nonlesioned), and sham tDCS-each for 20 mins. The primary outcome measures were Purdue pegboard test scores for hand dexterity and response time in the color-word Stroop test for selective attention. Pinch strength of the paretic hand was the secondary outcome. Cathodal tDCS to M1nonlesioned significantly improved affected hand dexterity (by 1.1 points on the Purdue pegboard unimanual test, P = 0.014) and selective attention (0.6 secs faster response time on the level 3 Stroop interference test for response inhibition, P = 0.017), but not pinch strength. The outcomes were not improved with anodal tDCS to M1lesioned or sham tDCS. Twenty minutes of cathodal tDCS to M1nonlesioned can promote both paretic hand dexterity and selective attention in people with chronic stroke.

Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human.

PubMed

Fonteneau, Clara; Redoute, Jérome; Haesebaert, Frédéric; Le Bars, Didier; Costes, Nicolas; Suaud-Chagny, Marie-Françoise; Brunelin, Jérome

2018-07-01

A single transcranial direct current stimulation (tDCS) session applied over the dorsolateral prefrontal cortex (DLFPC) can be associated with procognitive effects. Furthermore, repeated DLPFC tDCS sessions are under investigation as a new therapeutic tool for a range of neuropsychiatric conditions. A possible mechanism explaining such beneficial effects is a modulation of meso-cortico-limbic dopamine transmission. We explored the spatial and temporal neurobiological effects of bifrontal tDCS on subcortical dopamine transmission during and immediately after the stimulation. In a double blind sham-controlled study, 32 healthy subjects randomly received a single session of either active (20 min, 2 mA; n = 14) or sham (n = 18) tDCS during a dynamic positron emission tomography scan using [11C]raclopride binding. During the stimulation period, no significant effect of tDCS was observed. After the stimulation period, compared with sham tDCS, active tDCS induced a significant decrease in [11C]raclopride binding potential ratio in the striatum, suggesting an increase in extracellular dopamine in a part of the striatum involved in the reward-motivation network. The present study provides the first evidence that bifrontal tDCS induces neurotransmitter release in polysynaptic connected subcortical areas. Therefore, levels of dopamine activity and reactivity should be a new element to consider for a general hypothesis of brain modulation by bifrontal tDCS.

Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination

PubMed Central

Lüdtke, Anja; Ruibal, Paula; Wozniak, David M.; Pallasch, Elisa; Wurr, Stephanie; Bockholt, Sabrina; Gómez-Medina, Sergio; Qiu, Xiangguo; Kobinger, Gary P.; Rodríguez, Estefanía; Günther, Stephan; Krasemann, Susanne; Idoyaga, Juliana; Oestereich, Lisa; Muñoz-Fontela, César

2017-01-01

Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b+ DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103+ DC subset. Furthermore, depletion of CD8 and CD4 T cells resulted in loss of early control of virus replication, viremia and fatal Ebola virus disease (EVD). Thus, our findings point out at T cell function as a key determinant of EVD progress and outcome. PMID:28256637

Improving motor performance without training: the effect of combining mirror visual feedback with transcranial direct current stimulation.

PubMed

von Rein, Erik; Hoff, Maike; Kaminski, Elisabeth; Sehm, Bernhard; Steele, Christopher J; Villringer, Arno; Ragert, Patrick

2015-04-01

Mirror visual feedback (MVF) during motor training has been shown to improve motor performance of the untrained hand. Here we thought to determine if MVF-induced performance improvements of the left hand can be augmented by upregulating plasticity in right primary motor cortex (M1) by means of anodal transcranial direct current stimulation (a-tDCS) while subjects trained with the right hand. Participants performed a ball-rotation task with either their left (untrained) or right (trained) hand on two consecutive days (days 1 and 2). During training with the right hand, MVF was provided concurrent with two tDCS conditions: group 1 received a-tDCS over right M1 (n = 10), whereas group 2 received sham tDCS (s-tDCS, n = 10). On day 2, performance was reevaluated under the same experimental conditions compared with day 1 but without tDCS. While baseline performance of the left hand (day 1) was not different between groups, a-tDCS exhibited stronger MVF-induced performance improvements compared with s-tDCS. Similar results were observed for day 2 (without tDCS application). A control experiment (n = 8) with a-tDCS over right M1 as outlined above but without MVF revealed that left hand improvement was significantly less pronounced than that induced by combined a-tDCS and MVF. Based on these results, we provide novel evidence that upregulating activity in the untrained M1 by means of a-tDCS is capable of augmenting MVF-induced performance improvements in young normal volunteers. Our findings suggest that concurrent MVF and tDCS might have synergistic and additive effects on motor performance of the untrained hand, a result of relevance for clinical approaches in neurorehabilitation and/or exercise science. Copyright © 2015 the American Physiological Society.

Visualization of historical data for the ATLAS detector controls - DDV

NASA Astrophysics Data System (ADS)

Maciejewski, J.; Schlenker, S.

2017-10-01

The ATLAS experiment is one of four detectors located on the Large Hardon Collider (LHC) based at CERN. Its detector control system (DCS) stores the slow control data acquired within the back-end of distributed WinCC OA applications, which enables the data to be retrieved for future analysis, debugging and detector development in an Oracle relational database. The ATLAS DCS Data Viewer (DDV) is a client-server application providing access to the historical data outside of the experiment network. The server builds optimized SQL queries, retrieves the data from the database and serves it to the clients via HTTP connections. The server also implements protection methods to prevent malicious use of the database. The client is an AJAX-type web application based on the Vaadin (framework build around the Google Web Toolkit (GWT)) which gives users the possibility to access the data with ease. The DCS metadata can be selected using a column-tree navigation or a search engine supporting regular expressions. The data is visualized by a selection of output modules such as a java script value-over time plots or a lazy loading table widget. Additional plugins give the users the possibility to retrieve the data in ROOT format or as an ASCII file. Control system alarms can also be visualized in a dedicated table if necessary. Python mock-up scripts can be generated by the client, allowing the user to query the pythonic DDV server directly, such that the users can embed the scripts into more complex analysis programs. Users are also able to store searches and output configurations as XML on the server to share with others via URL or to embed in HTML.

The effects of medication use in transcranial direct current stimulation: A brief review.

PubMed

McLaren, Molly E; Nissim, Nicole R; Woods, Adam J

There has been increased interest in the potential use of transcranial direct current stimulation (tDCS) as treatment for multiple conditions including depression, pain, and cognitive impairment. However, few studies account for the possible influence of comorbid medications when conducting tDCS research. This literature review was conducted to examine what is currently known about the impact of medications on tDCS, provide recommendations for future research practices, and highlight areas where more research is needed. Key terms were searched in PubMed and Web of Science to identify studies that examine the impact of medication on tDCS effects in adults. Relevant papers' reference lists were also reviewed for thoroughness. Studies examined the effects of medication on 1 mA tDCS delivered to M1 (motor) and orbit/supraorbital (SO) area. All studies measured the effects of tDCS via MEP TMS paradigm. Results of the literature review suggest multiple classes of medications, including sodium and calcium channel blockers, and medications that influence various neurotransmitter systems (GABA, dopamine, serotonin, etc.) may all impact tDCS effects on tissue excitability. Research to date suggests multiple classes of medications may impact tDCS effects. These results highlight the importance of documenting medication use in research subjects and carefully considering what types of medications should be allowed into tDCS trials. Many questions still remain regarding the exact mechanisms of action for tDCS and how various parameters (medication dosages, tDCS stimulation intensity, etc.) may further impact the effects of medications on tDCS. Copyright © 2017 Elsevier Inc. All rights reserved.

Does d-cycloserine facilitate the effects of homework compliance on social anxiety symptom reduction?

PubMed

Roque, Andres D; Rosenfield, David; Smits, Jasper A J; Simon, Naomi; Otto, Michael W; Marques, Luana; Pollack, Mark H; Hofmann, Stefan G; Meuret, Alicia E

2018-01-01

Prior studies examining the effect of d-cycloserine (DCS) on homework compliance and outcome in cognitive-behavior therapy (CBT) have yielded mixed results. The aim of this study was to investigate whether DCS facilitates the effects of homework compliance on symptom reduction in a large-scale study for social anxiety disorder (SAD). 169 participants with generalized SAD received DCS or pill placebo during 12-session exposure-based group CBT. Improvements in social anxiety were assessed by independent raters at each session using the Liebowitz social anxiety scale (LSAS). Controlling for LSAS at the previous session, and irrespective of treatment condition, greater homework compliance in the week prior related to lower LSAS at the next session. However, DCS did not moderate the effect of homework compliance and LSAS, LSAS on homework compliance, or the overall augmenting effect of DCS on homework compliance. Furthermore, LSAS levels were not predictive of homework compliance in the following week. The findings support the general benefits of homework compliance on outcome, but not a DCS-augmenting effect. The comparably small number of DCS-enhanced sessions in this study could be one reason for the failure to find a facilitating effect of DCS. Copyright © 2017. Published by Elsevier Ltd.

Transcranial direct current stimulation over Broca's region improves phonemic and semantic fluency in healthy individuals.

PubMed

Cattaneo, Z; Pisoni, A; Papagno, C

2011-06-02

Previous studies have demonstrated that transcranial direct current stimulation (tDCS) can be proficiently used to modulate attentional and cognitive functions. For instance, in the language domain there is evidence that tDCS can fasten picture naming in both healthy individuals and aphasic patients, or improve grammar learning. In this study, we investigated whether tDCS can be used to increase healthy subjects' performance in phonemic and semantic fluency tasks, that are typically used in clinical assessment of language. Ten healthy individuals performed a semantic and a phonemic fluency task following anodal tDCS applied over Broca's region. Each participant underwent a real and a sham tDCS session. Participants were found to produce more words following real anodal tDCS both in the phonemic and in the semantic fluency. Control experiments ascertained that this finding did not depend upon unspecific effects of tDCS over levels of general arousal or attention or upon participants' expectations. These data confirm the efficacy of tDCS in transiently improving language functions by showing that anodal stimulation of Broca's region can enhance verbal fluency. Implications of these results for the treatment of language functions in aphasia are considered. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex enhances emotion recognition in depressed patients and controls.

PubMed

Brennan, Sean; McLoughlin, Declan M; O'Connell, Redmond; Bogue, John; O'Connor, Stephanie; McHugh, Caroline; Glennon, Mark

2017-05-01

Transcranial direct current stimulation (tDCS) can enhance a range of neuropsychological functions but its efficacy in addressing clinically significant emotion recognition deficits associated with depression is largely untested. A randomized crossover placebo controlled study was used to investigate the effects of tDCS over the left dorsolateral prefrontal cortex (L-DLPFC) on a range of neuropsychological variables associated with depression as well as neural activity in the associated brain region. A series of computerized tests was administered to clinical (n = 17) and control groups (n = 20) during sham and anodal (1.5 mA) stimulation. Anodal tDCS led to a significant main effect for overall emotion recognition (p = .02), with a significant improvement in the control group (p = .04). Recognition of disgust was significantly greater in the clinical group (p = .01). Recognition of anger was significantly improved for the clinical group (p = .04) during anodal stimulation. Differences between groups for each of the six emotions at varying levels of expression found that at 40% during anodal stimulation, happy recognition significantly improved for the clinical group (p = .01). Anger recognition at 80% during anodal stimulation significantly improved for the clinical group (p = .02). These improvements were observed in the absence of any change in psychomotor speed or trail making ability during anodal stimulation. Working memory significantly improved during anodal stimulation for the clinical group but not for controls (p = .03). The tentative findings of this study indicate that tDCS can have a neuromodulatory effect on a range of neuropsychological variables. However, it is clear that there was a wide variation in responses to tDCS and that individual difference and different approaches to testing and stimulation have a significant impact on final outcomes. Nonetheless, tDCS remains a promising tool for future neuropsychological research.

Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI.

PubMed

Wörsching, Jana; Padberg, Frank; Goerigk, Stephan; Heinz, Irmgard; Bauer, Christine; Plewnia, Christian; Hasan, Alkomiet; Ertl-Wagner, Birgit; Keeser, Daniel

2018-05-04

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking. This study investigated a priori hypotheses on specific effects of prefrontal-tDCS montages by using multimodal functional magnetic resonance imaging (fMRI) in healthy participants. 28 healthy male participants underwent three common active-tDCS montages and sham tDCS in a pseudo-randomized order, comprising a total of 112 tDCS-fMRI sessions. Active tDCS was applied at 2 mA for 20 min. Before and after tDCS, a resting-state fMRI (RS fMRI) was recorded, followed by a task fMRI with a delayed-response working-memory (DWM) task for assessing cognitive control over emotionally negative or neutral distractors. After tDCS with a cathode-F3/anode-F4 montage, RS-fMRI connectivity decreased in a medial part of the left PFC. Also, after the same stimulation condition, regional brain activity during DWM retrieval decreased more in this area after negative than after neutral distraction, and responses to the DWM task were faster, independent of distractor type. The current study does not confirm our a priori hypotheses on direction and localization of polarity-dependent tDCS effects using common bipolar electrode montages over PFC regions, but it provides evidence for montage-specific effects on multimodal neurophysiological and behavioral outcome measures. Systematic research on the actual targets and the respective dose-response relationships of prefrontal tDCS is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Dual-hemisphere transcranial direct current stimulation over primary motor cortex enhances consolidation of a ballistic thumb movement.

PubMed

Koyama, Soichiro; Tanaka, Satoshi; Tanabe, Shigeo; Sadato, Norihiro

2015-02-19

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates motor performance and learning. Previous studies have shown that tDCS over the primary motor cortex (M1) can facilitate consolidation of various motor skills. However, the effect of tDCS on consolidation of newly learned ballistic movements remains unknown. The present study tested the hypothesis that tDCS over M1 enhances consolidation of ballistic thumb movements in healthy adults. Twenty-eight healthy subjects participated in an experiment with a single-blind, sham-controlled, between-group design. Fourteen subjects practiced a ballistic movement with their left thumb during dual-hemisphere tDCS. Subjects received 1mA anodal tDCS over the contralateral M1 and 1mA cathodal tDCS over the ipsilateral M1 for 25min during the training session. The remaining 14 subjects underwent identical training sessions, except that dual-hemisphere tDCS was applied for only the first 15s (sham group). All subjects performed the task again at 1h and 24h later. Primary measurements examined improvement in peak acceleration of the ballistic thumb movement at 1h and 24h after stimulation. Improved peak acceleration was significantly greater in the tDCS group (144.2±15.1%) than in the sham group (98.7±9.1%) (P<0.05) at 24h, but not 1h, after stimulation. Thus, dual-hemisphere tDCS over M1 enhanced consolidation of ballistic thumb movement in healthy adults. Dual-hemisphere tDCS over M1 may be useful to improve elemental motor behaviors, such as ballistic movements, in patients with subcortical strokes. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Enhanced locomotor adaptation aftereffect in the “broken escalator” phenomenon using anodal tDCS

PubMed Central

Kaski, D.; Quadir, S.; Patel, M.; Yousif, N.

2012-01-01

The everyday experience of stepping onto a stationary escalator causes a stumble, despite our full awareness that the escalator is broken. In the laboratory, this “broken escalator” phenomenon is reproduced when subjects step onto an obviously stationary platform (AFTER trials) that was previously experienced as moving (MOVING trials) and attests to a process of motor adaptation. Given the critical role of M1 in upper limb motor adaptation and the potential for transcranial direct current stimulation (tDCS) to increase cortical excitability, we hypothesized that anodal tDCS over leg M1 and premotor cortices would increase the size and duration of the locomotor aftereffect. Thirty healthy volunteers received either sham or real tDCS (anodal bihemispheric tDCS; 2 mA for 15 min at rest) to induce excitatory effects over the primary motor and premotor cortex before walking onto the moving platform. The real tDCS group, compared with sham, displayed larger trunk sway and increased gait velocity in the first AFTER trial and a persistence of the trunk sway aftereffect into the second AFTER trial. We also used transcranial magnetic stimulation to probe changes in cortical leg excitability using different electrode montages and eyeblink conditioning, before and after tDCS, as well as simulating the current flow of tDCS on the human brain using a computational model of these different tDCS montages. Our data show that anodal tDCS induces excitability changes in lower limb motor cortex with resultant enhancement of locomotor adaptation aftereffects. These findings might encourage the use of tDCS over leg motor and premotor regions to improve locomotor control in patients with neurological gait disorders. PMID:22323638

Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols.

PubMed

Charvet, Leigh E; Kasschau, Margaret; Datta, Abhishek; Knotkova, Helena; Stevens, Michael C; Alonzo, Angelo; Loo, Colleen; Krull, Kevin R; Bikson, Marom

2015-01-01

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.

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

PubMed

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.

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

PubMed

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.

Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial.

PubMed

Levin, Mindy F; Baniña, Melanie C; Frenkel-Toledo, Silvi; Berman, Sigal; Soroker, Nachum; Solomon, John M; Liebermann, Dario G

2018-01-04

Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved ("active control zone") after identification of a "spasticity zone". Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function. This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task. This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries. ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.

Discovery of novel immunostimulants by dendritic-cell–based functional screening

PubMed Central

Mizumoto, Norikatsu; Gao, Jimin; Matsushima, Hironori; Ogawa, Yasushi; Tanaka, Hiroaki; Takashima, Akira

2005-01-01

Immunostimulants represent an emerging class of drugs for the treatment of infectious disorders and cancer. CpG oligonucleotides and imiquimod, prototypic drugs in this category, are now known to activate dendritic cells (DCs). Here we report the development of a highly sensitive, unbiased functional screen to detect DC-stimulatory signals. Because interleukin-1β (IL-1β) mRNA expression is closely associated with DC activation, we engineered DCs to stably express a fluorescent marker gene under the control of IL-1β promoter. By screening about 3000 compounds with the resulting DC biosensor clone, we identified DC-stimulatory potentials of topoisomerase I inhibitors (camptothecin derivatives) and microtubule depolymerizing drugs (colchicine and podophyllotoxin). In response to treatment with each agent, bone marrow–derived DC preparations exhibited characteristic phenotypic and/or functional changes associated with DC activation. All of these agents also triggered nuclear factor–κB (NFκB) activation in DCs, suggesting a common pharmacologic mechanism of action. Furthermore, locally administered colchicine induced in situ maturation and migration of DCs and augmented both humoral and cellular immune responses. These results support the practical utility of the DC-based biosensor system to discover novel DC-targeted immunostimulants and unveil previously unrecognized (and totally unexpected) pharmacologic activities of several drugs that are commonly used for the treatment of various disorders. PMID:16002424

The Bipolar Depression Electrical Treatment Trial (BETTER): Design, Rationale, and Objectives of a Randomized, Sham-Controlled Trial and Data from the Pilot Study Phase

PubMed Central

Pereira Junior, Bernardo de Sampaio; Nunes, Paula; Benseñor, Isabela Martins; Lotufo, Paulo Andrade; Machado-Vieira, Rodrigo; Brunoni, André R.

2015-01-01

Background. Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression. Methods. We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks. Results. In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores. Conclusion. This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS. PMID:25878904

Dose Timing of D-cycloserine to Augment Cognitive Behavioral Therapy for Social Anxiety: Study Design and Rationale

PubMed Central

Carpenter, Joseph K.; Otto, Michael W.; Rosenfield, David; Smits, Jasper A. J.; Pollack, Mark H.

2015-01-01

The use of d-cycloserine (DCS) as a cognitive enhancer to augment exposure-based cognitive-behavioral therapy (CBT) represents a promising new translational research direction with the goal to accelerate and optimize treatment response for anxiety disorders. Some studies suggest that DCS may not only augment extinction learning but could also facilitate fear memory reconsolidation. Therefore, the effect of DCS may depend on fear levels reported at the end of exposure sessions. This paper presents the rationale and design for an ongoing randomized controlled trial examining the relative efficacy of tailoring DCS administration based on exposure success (i.e. end fear levels) during a 5-session group CBT protocol for social anxiety disorder (n = 156). Specifically, tailored post-session DCS administration will be compared against untailored post-session DCS, untailored pre-session DCS, and pill placebo in terms of reduction in social anxiety symptoms and responder status. In addition, a subset of participants (n = 96) will undergo a fear extinction retention experiment prior to the clinical trial in which they will be randomly assigned to receive either DCS or placebo prior to extinguishing a conditioned fear. The results from this experimental paradigm will clarify the mechanism of the effects of DCS on exposure procedures. This study aims to serve as the first step toward developing an algorithm for the personalized use of DCS during CBT for social anxiety disorder, with the ultimate goal of optimizing treatment outcome for anxiety disorders. ClinicalTrials.gov identifier: NCT02066792 PMID:26111923

Dose timing of D-cycloserine to augment cognitive behavioral therapy for social anxiety: Study design and rationale.

PubMed

Hofmann, Stefan G; Carpenter, Joseph K; Otto, Michael W; Rosenfield, David; Smits, Jasper A J; Pollack, Mark H

2015-07-01

The use of D-cycloserine (DCS) as a cognitive enhancer to augment exposure-based cognitive-behavioral therapy (CBT) represents a promising new translational research direction with the goal to accelerate and optimize treatment response for anxiety disorders. Some studies suggest that DCS may not only augment extinction learning but could also facilitate fear memory reconsolidation. Therefore, the effect of DCS may depend on fear levels reported at the end of exposure sessions. This paper presents the rationale and design for a randomized controlled trial examining the relative efficacy of tailoring DCS administration based on exposure success (i.e. end fear levels) during a 5-session group CBT protocol for social anxiety disorder (n = 156). Specifically, tailored post-session DCS administration will be compared against untailored post-session DCS, untailored pre-session DCS, and pill placebo in terms of reduction in social anxiety symptoms and responder status. In addition, a subset of participants (n = 96) will undergo a fear extinction retention experiment prior to the clinical trial in which they will be randomly assigned to receive either DCS or placebo prior to extinguishing a conditioned fear. The results from this experimental paradigm will clarify the mechanism of the effects of DCS on exposure procedures. This study aims to serve as the first step toward developing an algorithm for the personalized use of DCS during CBT for social anxiety disorder, with the ultimate goal of optimizing treatment outcome for anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study.

PubMed

Wang, Chien-Yu; Chiao, Ming-Tsang; Yen, Po-Jen; Huang, Wei-Chou; Hou, Chia-Chung; Chien, Shih-Chang; Yeh, Kuo-Chen; Yang, Wen-Ching; Shyur, Lie-Fen; Yang, Ning-Sun

2006-12-01

Echinacea spp. are popularly used as an herbal medicine or food supplement for enhancing the immune system. This study shows that plant extracts from root [R] and stem plus leaf [S+L] tissues of E. purpurea exhibit opposite (enhancing vs inhibitory) modulatory effects on the expression of the CD83 marker in human dendritic cells (DCs), which are known as professional antigen-presenting cells. We developed a function-targeted DNA microarray system to characterize the effects of phytocompounds on human DCs. Down-regulation of mRNA expression of specific chemokines (e.g., CCL3 and CCL8) and their receptors (e.g., CCR1 and CCR9) was observed in [S+L]-treated DCs. Other chemokines and regulatory molecules (e.g., CCL4 and CCL2) involved in the c-Jun pathway were found to be up-regulated in [R]-treated DCs. This study, for the first time, demonstrates that E. purpurea extracts can modulate DC differentiation and expression of specific immune-related genes in DCs.

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

PubMed Central

Dudek, Aleksandra M.; Martin, Shaun; Garg, Abhishek D.; Agostinis, Patrizia

2013-01-01

Dendritic cells (DCs) are the sentinel antigen-presenting cells of the immune system; such that their productive interface with the dying cancer cells is crucial for proper communication of the “non-self” status of cancer cells to the adaptive immune system. Efficiency and the ultimate success of such a communication hinges upon the maturation status of the DCs, attained following their interaction with cancer cells. Immature DCs facilitate tolerance toward cancer cells (observed for many apoptotic inducers) while fully mature DCs can strongly promote anticancer immunity if they secrete the correct combinations of cytokines [observed when DCs interact with cancer cells undergoing immunogenic cell death (ICD)]. However, an intermediate population of DC maturation, called semi-mature DCs exists, which can potentiate either tolerogenicity or pro-tumorigenic responses (as happens in the case of certain chemotherapeutics and agents exerting ambivalent immune reactions). Specific combinations of DC phenotypic markers, DC-derived cytokines/chemokines, dying cancer cell-derived danger signals, and other less characterized entities (e.g., exosomes) can define the nature and evolution of the DC maturation state. In the present review, we discuss these different maturation states of DCs, how they might be attained and which anticancer agents or cell death modalities (e.g., tolerogenic cell death vs. ICD) may regulate these states. PMID:24376443

Damage control: Concept and implementation.

PubMed

Malgras, B; Prunet, B; Lesaffre, X; Boddaert, G; Travers, S; Cungi, P-J; Hornez, E; Barbier, O; Lefort, H; Beaume, S; Bignand, M; Cotte, J; Esnault, P; Daban, J-L; Bordes, J; Meaudre, E; Tourtier, J-P; Gaujoux, S; Bonnet, S

2017-12-01

The concept of damage control (DC) is based on a sequential therapeutic strategy that favors physiological restoration over anatomical repair in patients presenting acutely with hemorrhagic trauma. Initially described as damage control surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic trauma, this concept is articulated in three steps: surgical control of lesions (hemostasis, sealing of intestinal spillage), physiological restoration, then surgery for definitive repair. This concept was quickly adapted for intensive care management under the name damage control resuscitation (DCR), which refers to the modalities of hospital resuscitation carried out in patients suffering from traumatic hemorrhagic shock within the context of DCS. It is based mainly on specific hemodynamic resuscitation targets associated with early and aggressive hemostasis aimed at prevention or correction of the lethal triad of hypothermia, acidosis and coagulation disorders. Concomitant integration of resuscitation and surgery from the moment of admission has led to the concept of an integrated DCR-DCS approach, which enables initiation of hemostatic resuscitation upon arrival of the injured person, improving the patient's physiological status during surgery without delaying surgery. This concept of DC is constantly evolving; it stresses management of the injured person as early as possible, in order to initiate hemorrhage control and hemostatic resuscitation as soon as possible, evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and therapeutic radiological management under the name of radiological DC (DCRad). DCS is applied only to the most seriously traumatized patients, or in situations of massive influx of injured persons, as its universal application could lead to a significant and unnecessary excess-morbidity to injured patients who could and should undergo definitive treatment from the outset. DCS, when correctly applied, significantly improves the survival rate of war-wounded. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

PubMed

Costa, Nádia Lago; Gonçalves, Andréia Souza; Martins, Allisson Filipe Lopes; Arantes, Diego Antônio Costa; Silva, Tarcília Aparecida; Batista, Aline Carvalho

2016-07-01

There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms.

PubMed

Meinzer, Marcus; Lindenberg, Robert; Phan, Mai Thy; Ulm, Lena; Volk, Carina; Flöel, Agnes

2015-09-01

The long preclinical phase of Alzheimer's disease provides opportunities for potential disease-modifying interventions in prodromal stages such as mild cognitive impairment (MCI). Anodal transcranial direct current stimulation (anodal-tDCS), with its potential to enhance neuroplasticity, may allow improving cognition in MCI. In a double-blind, cross-over, sham-controlled study, anodal-tDCS was administered to the left inferior frontal cortex during task-related and resting-state functional magnetic resonance imaging (fMRI) to assess its impact on cognition and brain functions in MCI. During sham stimulation, MCI patients produced fewer correct semantic-word-retrieval responses than matched healthy controls, which was associated with hyperactivity in bilateral prefrontal regions. Anodal-tDCS significantly improved performance to the level of controls, reduced task-related prefrontal hyperactivity and resulted in "normalization" of abnormal network configuration during resting-state fMRI. Anodal-tDCS exerts beneficial effects on cognition and brain functions in MCI, thereby providing a framework to test whether repeated stimulation sessions may yield sustained reversal of cognitive deficits. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Direct Digital Boiler Control Systems for the Navy Small Boiler Equipment.

DTIC Science & Technology

1983-02-01

Hardware. Each full-size ACU a 6 caculation modules 30 arrme, modufes sation for dead time lag contains input/output circuit a 16 control mo uies a...along with lather modules of the DCS-1000 family. ’The complete instrument consists of plug-in circuit boards that allow easy Teplacement of a...Maintenance-Most systems indicate trouble areas with diagnostic routines or integral LED indicators so that circuit boards can be replaced to correct

Human 6-sulfo LacNAc (slan) dendritic cells have molecular and functional features of an important pro-inflammatory cell type in lupus erythematosus.

PubMed

Hänsel, Anja; Günther, Claudia; Baran, Wojciech; Bidier, Mona; Lorenz, Hanns-Martin; Schmitz, Marc; Bachmann, Michael; Döbel, Thomas; Enk, Alexander H; Schäkel, Knut

2013-02-01

Lupus erythematosus (LE) is an autoimmune disease with evidence for an IL-23- and IL-17-induced immunopathology. Little is known about the type of dendritic cells supporting this immune response. We recently demonstrated the strong Th1- and Th17-T-cell inducing capacity of human 6-sulfo LacNAc-dendritic cells (slanDCs), and identified slanDCs as inflammatory dermal dendritic cells in psoriasis locally expressing IL-23, TNF-α and inducible nitric oxide synthase (iNOS). In this study, we investigated the role of slanDCs in LE. Using immunohistochemistry, we identified slanDCs at increased frequency in affected skin lesions of cutaneous and systemic LE. slanDCs were found scattered in the dermal compartment and also clustered in lymph follicle-like structures. Here, they colocalized with T cells in the periphery but not with B cells in the center. The positive staining of dermal slanDCs for TNF-α indicated their pro-inflammatory status. In vitro the production of TNF-α was induced when slanDCs were cultured in the presence of serum from patients with LE. Stimulatory components of LE serum were previously identified as autoimmune complexes with ssRNA binding to TLR7 and TLR8. We found that slanDCs express mRNA for TLR7 and TLR8. slanDCs stimulated with ssRNA, selective TLR7 or TLR8 ligands responded with high-level TNF-α and IL-12 production. In contrast to slanDCs, the population of CD1c(+) DCs and plasmacytoid DCs (pDCs) expressed either TLR7 or TLR8, and their production of TNF-α and IL-12 to respective ligands was far less pronounced. We conclude that slanDCs have molecular and functional features of a pro-inflammatory myeloid DC type relevant for the immunopathogenesis of LE. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Trouble Brewing: Using Observations of Invariant Behavior to Detect Malicious Agency in Distributed Control Systems

NASA Astrophysics Data System (ADS)

McEvoy, Thomas Richard; Wolthusen, Stephen D.

Recent research on intrusion detection in supervisory data acquisition and control (SCADA) and DCS systems has focused on anomaly detection at protocol level based on the well-defined nature of traffic on such networks. Here, we consider attacks which compromise sensors or actuators (including physical manipulation), where intrusion may not be readily apparent as data and computational states can be controlled to give an appearance of normality, and sensor and control systems have limited accuracy. To counter these, we propose to consider indirect relations between sensor readings to detect such attacks through concurrent observations as determined by control laws and constraints.

Effect of ginseng polysaccharides and dendritic cells on the balance of Th1/Th2 T helper cells in patients with non-small cell lung cancer.

PubMed

Ma, Junjie; Liu, Huiping; Wang, Xiaolong

2014-12-01

To investigate the effect of thorascopic administration.of ginseng polysaccharides (GPS) plus dendritic cells (DC) on T helper cell type 1/T helper cell type 2 (Th1/Th2) balance in patients with non-small cell lung cancer (NSCLC). A total of 96 NSCLC patients were divided evenly into two groups. The control group was treated with DCs alone and the treatment group was treated with DCs plus GPS. After DCs and GPS were administered thoracoscopically, once a week, 4 times for 30 days, the patients' quality of life was measured with the Functional Assessment of Cancer Treatment-Lung (FACT-L) questionnaire before and after treatment. Serum interferon-γ (INF-γ), interleukin-4 (IL-4), IL-2 and IL-5 were examined before and after treatments. The level of Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 cytokines (INF-γ/IL-4, IL-2/ IL-5) increased in both treatment groups, while Th2 cytokines (IL-4, IL-5) and FACT-L scores decreased (P < 0.01). Furthermore, after treatment Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 cytokines (INF-γ/IL-4, IL-2/IL-5) were higher in the DCs + GPS group than in the control group (P < 0.05). Conversely, FACT-L scores and Th2 cytokines (IL-4, IL-5) were higher in the control group than in the DCs + GPS group (P < 0.05). The treatment regime of DCs plus GPS had a greater effect on NSCLC patients' immune function as compared with DCs alone. This was evident by increased expression of Th1 cytokines (INF-γ, IL-2) and the ratio of Th1/Th2 (INF-γ/IL-4, IL-2/IL-5), as well as by decreased FACT-L scores and the expression of Th2 cytokines (IL-4, IL-5).

Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data

PubMed Central

Brunoni, André R.; Moffa, Adriano H.; Fregni, Felipe; Palm, Ulrich; Padberg, Frank; Blumberger, Daniel M.; Daskalakis, Zafiris J.; Bennabi, Djamila; Haffen, Emmanuel; Alonzo, Angelo; Loo, Colleen K.

2016-01-01

Background Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention for depression. It has mixed results, possibly caused by study heterogeneity. Aims To assess tDCS efficacy and to explore individual response predictors. Method Systematic review and individual patient data meta-analysis. Results Data were gathered from six randomised sham-controlled trials, enrolling 289 patients. Active tDCS was significantly superior to sham for response (34% v. 19% respectively, odds ratio (OR) = 2.44, 95% CI 1.38–4.32, number needed to treat (NNT) = 7), remission (23.1% v. 12.7% respectively, OR = 2.38, 95% CI 1.22–4.64, NNT = 9) and depression improvement (B coefficient 0.35, 95% CI 0.12–0.57). Mixed-effects models showed that, after adjustment for other predictors and confounders, treatment-resistant depression and higher tDCS ‘doses’ were, respectively, negatively and positively associated with tDCS efficacy. Conclusions The effect size of tDCS treatment was comparable with those reported for repetitive transcranial magnetic stimulation and antidepressant drug treatment in primary care. The most important parameters for optimisation in future trials are depression refractoriness and tDCS dose. PMID:27056623

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

PubMed

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.

Flat-plate collector research area: Silicon material task

NASA Technical Reports Server (NTRS)

Lutwack, R.

1982-01-01

Silane decomposition in a fluidized-bed reactor (FBR) process development unit (PDU) to make semiconductor-grade Si is reviewed. The PDU was modified by installation of a new heating system to provide the required temperature profile and better control, and testing was resumed. A process for making trichlorosilane by the hydrochlorination of metallurgical-grade Si and silicon tetrachloride is reported. Fabrication and installation of the test system employing a new 2-in.-dia reactor was completed. A process that converts trichlorosilane to dichlorosilane (DCS), which is reduced by hydrogen to make Si by a chemical vapor deposition step in a Siemens-type reactor is described. Testing of the DCS PDU integraled with Si deposition reactors continued. Experiments in a 2-in.-dia reactor to define the operating window and to investigate the Si deposition kinetics were completed.

Safety and feasibility of transcranial direct current stimulation (tDCS) combined with sensorimotor retraining in chronic low back pain: a protocol for a pilot randomised controlled trial.

PubMed

Ouellette, Adam Louis; Liston, Matthew B; Chang, Wei-Ju; Walton, David M; Wand, Benedict Martin; Schabrun, Siobhan M

2017-08-21

Chronic low back pain (LBP) is a common and costly health problem yet current treatments demonstrate at best, small effects. The concurrent application of treatments with synergistic clinical and mechanistic effects may improve outcomes in chronic LBP. This pilot trial aims to (1) determine the feasibility, safety and perceived patient response to a combined transcranial direct current stimulation (tDCS) and sensorimotor retraining intervention in chronic LBP and (2) provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. A pilot randomised, assessor and participant-blind, sham-controlled trial will be conducted. Eighty participants with chronic LBP will be randomly allocated to receive either (1) active tDCS + sensorimotor retraining or (2) sham tDCS + sensorimotor retraining. tDCS (active or sham) will be applied to the primary motor cortex for 20 min immediately prior to 60 min of supervised sensorimotor retraining twice per week for 10 weeks. Participants in both groups will complete home exercises three times per week. Feasibility, safety, pain, disability and pain system function will be assessed immediately before and after the 10-week intervention. Analysis of feasibility and safety will be performed using descriptive statistics. Statistical analyses will be conducted based on intention-to-treat and per protocol and will be used to determine trends for effectiveness. Ethical approval has been gained from the institutional human research ethics committee (H10184). Written informed consent will be provided by all participants. Results from this pilot study will be submitted for publication in peer-reviewed journals. ACTRN12616000624482. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Acute, but not chronic, exposure to d-cycloserine facilitates extinction and modulates spontaneous recovery of a conditioned taste aversion.

PubMed

Mickley, G Andrew; Remus, Jennifer L; Ramos, Linnet; Wilson, Gina N; Biesan, Orion R; Ketchesin, Kyle D

2012-01-18

D-cycloserine, the glutamate N-methyl-D-aspartate receptor partial agonist, has been reported to facilitate the extinction of learned fears acquired in both naturalistic and laboratory settings. The current study extended this literature by evaluating the ability of either chronic or acute administrations of DCS to modulate the extinction and spontaneous recovery of a conditioned taste aversion (CTA). Twenty-three hour fluid-deprived Sprague-Dawley rats acquired a strong CTA following 3 pairings of a conditioned stimulus (CS; 0.3% oral saccharin)+unconditioned stimulus [US; 81 mg/kg (i.p.) lithium chloride (LiCl)]. In separate groups of rats, we then employed 2 different extinction paradigms: (1) CS-only (CSO-EXT) in which saccharin was presented every-other day, or (2) Explicitly Unpaired (EU-EXT) in which both saccharin and LiCl were presented but on alternate days. Previous studies have indicated that the EU-EXT procedure speeds up the extinction process. Further, spontaneous recovery of a CTA emerges following CSO-EXT but the EU-EXT paradigm causes a suppression of spontaneous recovery. DCS (15 mg/kg, i.p.) was administered immediately after daily liquid presentations (saccharin or water, alternate days) during the extinction period. In an acute drug manipulation, DCS (15 mg/kg, i.p.) or saline control injections were administered for 4 days only. This was done during one of 3 different phases of extinction [i.e., static (2-5%), early dynamic (8-16%), or middle dynamic (20-40%) saccharin reacceptance]. Other animals assigned to the chronic DCS condition received daily DCS (15 mg/kg, i.p.) throughout extinction. Changes in saccharin drinking in these animals were compared to the data from rats that received no drug (saline controls). Once rats met our criterion for asymptotic extinction (90% reacceptance of the CS) they entered a 30-day latency period during which they received water for 1 h/day. The day after the completion of the latency period, a final opportunity to drink saccharin was provided (spontaneous recovery test). Saline-treated control rats that went through the EU-EXT procedure achieved asymptotic extinction more quickly than did the CSO-EXT rats and did not exhibit a spontaneous recovery of the CTA. Chronic DCS treatments did not significantly reduce the time to achieve asymptotic CTA extinction in rats exposed to either CSO or EU extinction methods. Further, animals treated with DCS throughout EU-EXT exhibited a spontaneous recovery of the CTA whereas the saline-treated, EU-EXT rats did not. Thus, chronic DCS treatment did not shorten the time to extinguish a CTA and this treatment eliminated the ability of EU-EXT to block spontaneous recovery of the CTA. Acute DCS treatments were more effective in reducing the time required to extinguish a CTA than were chronic drug treatments. Moreover, the timing of these acute DCS treatments affected spontaneous recovery of the CTA depending on the extinction method employed. Acute DCS administrations later in extinction were more effective in reducing spontaneous recovery than were early administrations if the rats went through the CSO-EXT procedure. However, late-in-extinction administrations of DCS facilitated spontaneous recovery of the CTA in rats that experienced the EU-EXT method. These data agree with other findings suggesting that DCS treatments are more effective when administered a limited number of times. Our data extend these findings to the CTA paradigm and further suggest that, depending on the extinction paradigm employed, acute exposure to DCS can speed up CTA extinction and reduce spontaneous recovery of the aversion. The timing of the acute DCS treatment during extinction is generally less important than its duration in predicting the rate of CTA extinction. However, the timing of acute DCS treatments during extinction and the method of extinction employed can interact to affect spontaneous recovery of a CTA. Copyright © 2011 Elsevier Inc. All rights reserved.

A comparison of the effects of transcranial direct current stimulation and caffeine on vigilance and cognitive performance during extended wakefulness.

PubMed

McIntire, Lindsey K; McKinley, R Andy; Goodyear, Chuck; Nelson, Justin

2014-01-01

Sleep deprivation from extended duty hours is a common complaint for many occupations. Caffeine is one of the most common countermeasures used to combat fatigue. However, the benefits of caffeine decline over time and with chronic use. Our objective was to evaluate the efficacy of anodal transcranial direct current stimulation (tDCS) applied to the pre-frontal cortex at 2 mA for 30 min to remediate the effects of sleep deprivation and to compare the behavioral effects of tDCS with those of caffeine. Three groups of 10 participants each received either active tDCS with placebo gum, caffeine gum with sham tDCS, or sham tDCS with placebo gum during 30 h of extended wakefulness. Our results show that tDCS prevented a decrement in vigilance and led to better subjective ratings for fatigue, drowsiness, energy, and composite mood compared to caffeine and control in sleep-deprived individuals. Both the tDCS and caffeine produced similar improvements in latencies on a short-term memory task and faster reaction times in a psychomotor task when compared to the placebo group. Interestingly, changes in accuracy for the tDCS group were not correlated to changes in mood; whereas, there was a relationship for the caffeine and sham groups. Our data suggest that tDCS could be a useful fatigue countermeasure and may be more beneficial than caffeine since boosts in performance and mood last several hours. Published by Elsevier Inc.

Effects of Transcranial Direct Current Stimulation on Neural Networks in Young and Older Adults

PubMed

Martin, Andrew K; Meinzer, Marcus; Lindenberg, Robert; Sieg, Mira M; Nachtigall, Laura; Flöel, Agnes

2017-11-01

Transcranial direct current stimulation (tDCS) may be a viable tool to improve motor and cognitive function in advanced age. However, although a number of studies have demonstrated improved cognitive performance in older adults, other studies have failed to show restorative effects. The neural effects of beneficial stimulation response in both age groups is lacking. In the current study, tDCS was administered during simultaneous fMRI in 42 healthy young and older participants. Semantic word generation and motor speech baseline tasks were used to investigate behavioral and neural effects of uni- and bihemispheric motor cortex tDCS in a three-way, crossover, sham tDCS controlled design. Independent components analysis assessed differences in task-related activity between the two age groups and tDCS effects at the network level. We also explored whether laterality of language network organization was effected by tDCS. Behaviorally, both active tDCS conditions significantly improved semantic word retrieval performance in young and older adults and were comparable between groups and stimulation conditions. Network-level tDCS effects were identified in the ventral and dorsal anterior cingulate networks in the combined sample during semantic fluency and motor speech tasks. In addition, a shift toward enhanced left laterality was identified in the older adults for both active stimulation conditions. Thus, tDCS results in common network-level modulations and behavioral improvements for both age groups, with an additional effect of increasing left laterality in older adults.

Dendritic cells from the elderly display an intrinsic defect in the production of IL-10 in response to lithium chloride.

PubMed

Agrawal, Sudhanshu; Gollapudi, Sastry; Gupta, Sudhir; Agrawal, Anshu

2013-11-01

Chronic, low grade inflammation is a characteristic of old age. Innate immune system cells such as dendritic cells (DCs) from the elderly display a pro-inflammatory phenotype associated with increased reactivity to self. Lithium is a well-established anti-inflammatory agent used in the treatment of bipolar disorders. It has also been reported to reduce inflammation in DCs. Here, we investigated whether Lithium is effective in reducing the inflammatory responses in DCs from the elderly. The effect of Lithium Chloride (LiCl) was compared on the response of TLR4 agonist, LPS and TLR2 agonist, PAM3CSK4 stimulated aged and young DCs. LiCl enhanced the production of IL-10 in LPS stimulated young DCs. However, it did not affect TNF-α and IL-6 production. In contrast, in aged DCs, LiCl reduced the secretion of TNF-α and IL-6 in LPS stimulated DCs but did not increase IL-10. LiCl had no significant effect on PAM3CSK4 responses in aged and young DCs. LiCl treated DCs also displayed differences at the level of CD4 T cell priming and polarization. LPS-stimulated young DCs reduced IFN-γ secretion and biased the Th cell response towards Th2/Treg while LiCl treated aged DCs only reduced IFN-γ secretion but did not bias the response towards Th2/Treg. In summary, our data suggests that LiCl reduces inflammation in aged and young DCs via different mechanisms. Furthermore, the effect of LiCl is different on LPS and PAM3CSK4 responses. © 2013.

Earth Observatory Satellite system definition study. Report 5: System design and specifications. Volume 5: Specification for EROS operations control center

NASA Technical Reports Server (NTRS)

1974-01-01

The functional, performance, and design requirements for the Operations Control Center (OCC) of the Earth Observatory Satellite (EOS) system are presented. The OCC controls the operations of the EOS satellite to acquire mission data consisting of: (1) thematic mapper data, (2) multispectral scanner data on EOS-A, or High Resolution Pointable Imager data on EOS-B, and (3) data collection system (DCS) data. The various inputs to the OCC are identified. The functional requirements of the OCC are defined. The specific systems and subsystems of the OCC are described and block diagrams are provided.

How Does Anodal Transcranial Direct Current Stimulation of the Pain Neuromatrix Affect Brain Excitability and Pain Perception? A Randomised, Double-Blind, Sham-Control Study

PubMed Central

Vaseghi, Bita; Zoghi, Maryam; Jaberzadeh, Shapour

2015-01-01

Background Integration of information between multiple cortical regions of the pain neuromatrix is thought to underpin pain modulation. Although altered processing in the primary motor (M1) and sensory (S1) cortices is implicated in separate studies, the simultaneous changes in and the relationship between these regions are unknown yet. The primary aim was to assess the effects of anodal transcranial direct current stimulation (a-tDCS) over superficial regions of the pain neuromatrix on M1 and S1 excitability. The secondary aim was to investigate how M1 and S1 excitability changes affect sensory (STh) and pain thresholds (PTh). Methods Twelve healthy participants received 20 min a-tDCS under five different conditions including a-tDCS of M1, a-tDCS of S1, a-tDCS of DLPFC, sham a-tDCS, and no-tDCS. Excitability of dominant M1 and S1 were measured before, immediately, and 30 minutes after intervention respectively. Moreover, STh and PTh to peripheral electrical and mechanical stimulation were evaluated. All outcome measures were assessed at three time-points of measurement by a blind rater. Results A-tDCS of M1 and dorsolateral prefrontal cortex (DLPFC) significantly increased brain excitability in M1 (p < 0.05) for at least 30 min. Following application of a-tDCS over the S1, the amplitude of the N20-P25 component of SEPs increased immediately after the stimulation (p < 0.05), whilst M1 stimulation decreased it. Compared to baseline values, significant STh and PTh increase was observed after a-tDCS of all three stimulated areas. Except in M1 stimulation, there was significant PTh difference between a-tDCS and sham tDCS. Conclusion a-tDCS of M1 is the best spots to enhance brain excitability than a-tDCS of S1 and DLPFC. Surprisingly, a-tDCS of M1 and S1 has diverse effects on S1 and M1 excitability. A-tDCS of M1, S1, and DLPFC increased STh and PTh levels. Given the placebo effects of a-tDCS of M1 in pain perception, our results should be interpreted with caution, particularly with respect to the behavioural aspects of pain modulation. Trial Registration Australian New Zealand Clinical Trials, ACTRN12614000817640, http://www.anzctr.org.au/. PMID:25738603

Modulation of selective attention by polarity-specific tDCS effects.

PubMed

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.

Tagging motor memories with transcranial direct current stimulation allows later artificially-controlled retrieval

PubMed Central

Nozaki, Daichi; Yokoi, Atsushi; Kimura, Takahiro; Hirashima, Masaya; Orban de Xivry, Jean-Jacques

2016-01-01

We demonstrate that human motor memories can be artificially tagged and later retrieved by noninvasive transcranial direct current stimulation (tDCS). Participants learned to adapt reaching movements to two conflicting dynamical environments that were each associated with a different tDCS polarity (anodal or cathodal tDCS) on the sensorimotor cortex. That is, we sought to determine whether divergent background activity levels within the sensorimotor cortex (anodal: higher activity; cathodal: lower activity) give rise to distinct motor memories. After a training session, application of each tDCS polarity automatically resulted in the retrieval of the motor memory corresponding to that polarity. These results reveal that artificial modulation of neural activity in the sensorimotor cortex through tDCS can act as a context for the formation and recollection of motor memories. DOI: http://dx.doi.org/10.7554/eLife.15378.001 PMID:27472899

Transcranial direct current stimulation in post-stroke sub-acute aphasia: study protocol for a randomized controlled trial.

PubMed

Spielmann, Kerstin; van de Sandt-Koenderman, W Mieke E; Heijenbrok-Kal, Majanka H; Ribbers, Gerard M

2016-08-02

Transcranial direct current stimulation (tDCS) is a promising new technique to optimize the effect of regular Speech and Language Therapy (SLT) in the context of aphasia rehabilitation. The present study focuses on the effect of tDCS provided during SLT in the sub-acute stage after stroke. The primary aim is to evaluate the potential effect of tDCS on language functioning, specifically on word-finding, as well as generalization effects to verbal communication. The secondary aim is to evaluate its effect on social participation and quality of life, and its cost-effectiveness. We strive to include 58 stroke patients with aphasia, enrolled in an inpatient or outpatient stroke rehabilitation program, in a multicenter, double-blind, randomized controlled trial with two parallel groups and 6 months' follow-up. Patients will participate in two separate intervention weeks, with a pause of 2 weeks in between, in the context of their regular aphasia rehabilitation program. The two intervention weeks comprise daily 45-minute sessions of word-finding therapy, combined with either anodal tDCS over the left inferior frontal gyrus (1 mA, 20 minutes; experimental condition) or sham-tDCS over the same region (control condition). The primary outcome measure is word-finding. Secondary outcome measures are verbal communication, social participation, quality of life, and cost-effectiveness of the intervention. Our results will contribute to the discussion on whether tDCS should be implemented in regular aphasia rehabilitation programs for the sub-acute post-stroke population in terms of (cost-)effectiveness. Nederlands Trail Register: NTR4364 . Registered on 21 February 2014.

A Meta-Analysis of D-Cycloserine in Exposure-Based Treatment: Moderators of Treatment Efficacy, Response, and Diagnostic Remission

PubMed Central

McGuire, Joseph F.; Wu, Monica S.; Piacentini, John; McCracken, James T.; Storch, Eric A.

2018-01-01

Objective This meta-analysis examined treatment efficacy, treatment response, and diagnostic remission effect sizes (ES) and moderators of d-cycloserine (DCS) augmented exposure treatment in randomized controlled trials (RCTs) of individuals with anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). Data Sources and Study Selection Using search terms d-cycloserine AND randomized controlled trial, PubMED (1965-May 2015), PsycInfo, and Scopus were searched for randomized placebo-controlled trials of DCS-augmented exposure therapy for anxiety disorders, OCD, and PTSD. Data Extraction Clinical variables and ES were extracted from 20 RCTs (957 participants). A random effects model calculated the ES for treatment efficacy, treatment response, and diagnostic remission using standardized rating scales. Subgroup analyses and meta-regression examined potential moderators. Results A small non-significant benefit of DCS augmentation compared to placebo augmentation was identified across treatment efficacy (g=0.15), response (RR=1.08), and remission (RR=1.109), with a moderately significant effect for anxiety disorders specifically (g=0.33, p=.03). At initial follow-up assessments, a small non-significant ES of DCS augmentation compared to placebo was found for treatment efficacy (g=0.21), response (RR=1.06), and remission (RR=1.12). Specific treatment moderators (e.g., comorbidity, medication status, gender, publication year) were found across conditions for both acute treatment and initial follow-up assessments. Conclusions DCS does not universally enhance treatment outcomes, but demonstrates promise for anxiety disorders. Distinct treatment moderators may account for discrepant findings across RCTs and disorders. Future trials may be strengthened by accounting for identified moderators in their design, with ongoing research needed on the mechanisms of DCS to tailor treatment protocols and maximize its benefit. PMID:27314661

Switchgrass and Miscanthus Biomass and Theoretical Ethanol Production from Reclaimed Mine Lands in West Virginia

NASA Astrophysics Data System (ADS)

Scagline, Steffany M.

Near infrared stimulation or Low Level Laser Therapy (LLLT) is an innovative technique shown to effect the microvasculature hemodynamics. The aim of this study is to use Diffused Correlation Spectroscopy (DCS) to evaluate the physiological effects of LLLT on blood perfusion. This study is divided into two parts: the fist part is the development of DCS system and the second part is investigating the effects of LLLT on biological tissue. DCS is an emerging non-invasive technique to probe deep tissue hemodynamics. DCS uses time-averaged intensity autocorrelation function for the fluctuations caused due to the moving scatterers (RBCs) in biological tissue. We present a software based autocorrelator system to complete the acquisition and processing parts. We conducted validation studies on an intralipid phantom and human forearm. Both the studies proved smooth decay curves which help in getting a better curve fitting and as a result more accurate blood flow index (BFI). We show that the software based autocorrelation system can be an alternative to the conventional hardware based correlators in DCS systems with benefits such as flexibility in raw photon count data processing and low cost. The objective of the second part of this study is evaluating how a single session of LLLT alters the hemodynamics in the microvasculature. We performed an experiment where the subjects forearm was stimulated with LLLT and the corresponding changes were recorded using DCS system. The results obtained shows significant hemodynamic changes in response to LLLT with a 95%confidence interval. The results in this study indicate that LLLT could lead to the development of non-invasive technique to help in rehabilitation and performance-enhancing of healthy humans.

CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

PubMed Central

Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

2012-01-01

Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients

PubMed Central

Cavaliere, Carlo; Aiello, Marco; Di Perri, Carol; Amico, Enrico; Martial, Charlotte; Thibaut, Aurore; Laureys, Steven; Soddu, Andrea

2016-01-01

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 exist, 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 (ECN) and default-mode network (DMN) 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 (NR) 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 ECN 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. PMID:27857682

Can Transcranial Direct Current Stimulation Improve Cognitive Functioning in Adults with Schizophrenia?

PubMed

Schretlen, David J; van Steenburgh, Joseph J; Varvaris, Mark; Vannorsdall, Tracy D; Andrejczuk, Megan A; Gordon, Barry

Cognitive impairment is nearly ubiquitous in schizophrenia. First-degree relatives of persons with schizophrenia often show similar but milder deficits. Current methods for the treatment of schizophrenia are often ineffective in cognitive remediation. Since transcranial direct current stimulation (tDCS) can enhance cognitive functioning in healthy adults, it might provide a viable option to enhance cognition in schizophrenia. We sought to explore whether tDCS can be tolerated by persons with schizophrenia and potentially improve their cognitive functioning. We examined the effects of anodal versus cathodal tDCS on working memory and other cognitive tasks in five outpatients with schizophrenia and six first-degree relatives of persons with schizophrenia. Each participant completed tasks thought to be mediated by the prefrontal cortex during two 30-minute sessions of tDCS to the left and right dorsolateral prefrontal cortex (DLPFC). Anodal stimulation over the left DLPFC improved performance relative to cathodal stimulation on measures of working memory and aspects of verbal fluency relevant to word retrieval. The patient group showed differential changes in novel design production without alteration of overall productivity, suggesting that tDCS might be capable of altering self-monitoring and executive control. All participants tolerated tDCS well. None withdrew from the study or experienced any adverse reaction. We conclude that adults with schizophrenia can tolerate tDCS while engaging in cognitive tasks and that tDCS can alter their performance.

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients.

PubMed

Cavaliere, Carlo; Aiello, Marco; Di Perri, Carol; Amico, Enrico; Martial, Charlotte; Thibaut, Aurore; Laureys, Steven; Soddu, Andrea

2016-01-01

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 exist, 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 (ECN) and default-mode network (DMN) 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 (NR) 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 ECN 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.

Wearable functional near infrared spectroscopy (fNIRS) and transcranial direct current stimulation (tDCS): expanding vistas for neurocognitive augmentation

PubMed Central

McKendrick, Ryan; Parasuraman, Raja; Ayaz, Hasan

2015-01-01

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. PMID:25805976

Combining D-cycloserine with appetitive extinction learning modulates amygdala activity during recall.

PubMed

Ebrahimi, Claudia; Koch, Stefan P; Friedel, Eva; Crespo, Ilsoray; Fydrich, Thomas; Ströhle, Andreas; Heinz, Andreas; Schlagenhauf, Florian

2017-07-01

Appetitive Pavlovian conditioning plays a crucial role in the pathogenesis of drug addiction and conditioned reward cues can trigger craving and relapse even after long phases of abstinence. Promising preclinical work showed that the NMDA-receptor partial agonist D-cycloserine (DCS) facilitates Pavlovian extinction learning of fear and drug cues. Furthermore, DCS-augmented exposure therapy seems to be beneficial in various anxiety disorders, while the supposed working mechanism of DCS during human appetitive or aversive extinction learning is still not confirmed. To test the hypothesis that DCS administration before extinction training improves extinction learning, healthy adults (n=32) underwent conditioning, extinction, and extinction recall on three successive days in a randomized, double-blind, placebo-controlled fMRI design. Monetary wins and losses served as unconditioned stimuli during conditioning to probe appetitive and aversive learning. An oral dose of 50mg of DCS or placebo was administered 1h before extinction training and DCS effects during extinction recall were evaluated on a behavioral and neuronal level. We found attenuated amygdala activation in the DCS compared to the placebo group during recall of the extinguished appetitive cue, along with evidence for enhanced functional amygdala-vmPFC coupling in the DCS group. While the absence of additional physiological measures of conditioned responses during recall in this study prevent the evaluation of a behavioral DCS effect, our neuronal findings are in accordance with recent theories linking successful extinction recall in humans to modulatory top-down influences from the vmPFC that inhibit amygdala activation. Our results should encourage further translational studies concerning the usefulness of DCS to target maladaptive Pavlovian reward associations. Copyright © 2017 Elsevier Inc. All rights reserved.

Delayed enhancement of multitasking performance: Effects of anodal transcranial direct current stimulation on the prefrontal cortex

PubMed Central

Hsu, Wan-Yu; Zanto, Theodore P.; Anguera, Joaquin A.; Lin, Yung-Yang; Gazzaley, Adam

2015-01-01

Background The dorsolateral prefrontal cortex (DLPFC) has been proposed to play an important role in neural processes that underlie multitasking performance. However, this claim is underexplored in terms of direct causal evidence. Objective The current study aimed to delineate the causal involvement of the DLPFC during multitasking by modulating neural activity with transcranial direct current stimulation (tDCS) prior to engagement in a demanding multitasking paradigm. Methods The study is a single-blind, crossover, sham-controlled experiment. Anodal tDCS or sham tDCS was applied over left DLPFC in forty-one healthy young adults (aged 18–35 years) immediately before they engaged in a 3-D video game designed to assess multitasking performance. Participants were separated into three subgroups: real-sham (i.e., real tDCS in the first session, followed by sham tDCS in the second session one hour later), sham-real (sham tDCS first session, real tDCS second session), and sham-sham (sham tDCS in both sessions). Results The real-sham group showed enhanced multitasking performance and decreased multitasking cost during the second session, compared to first session, suggesting delayed cognitive benefits of tDCS. Interestingly, performance benefits were observed only for multitasking and not on a single-task version of the game. No significant changes were found between the first and second sessions for either the sham-real or the sham-sham groups. Conclusions These results suggest a causal role of left prefrontal cortex in facilitating the simultaneous performance of more than one task, or multitasking. Moreover, these findings reveal that anodal tDCS may have delayed benefits that reflect an enhanced rate of learning. PMID:26073148

Delayed enhancement of multitasking performance: Effects of anodal transcranial direct current stimulation on the prefrontal cortex.

PubMed

Hsu, Wan-Yu; Zanto, Theodore P; Anguera, Joaquin A; Lin, Yung-Yang; Gazzaley, Adam

2015-08-01

The dorsolateral prefrontal cortex (DLPFC) has been proposed to play an important role in neural processes that underlie multitasking performance. However, this claim is underexplored in terms of direct causal evidence. The current study aimed to delineate the causal involvement of the DLPFC during multitasking by modulating neural activity with transcranial direct current stimulation (tDCS) prior to engagement in a demanding multitasking paradigm. The study is a single-blind, crossover, sham-controlled experiment. Anodal tDCS or sham tDCS was applied over left DLPFC in forty-one healthy young adults (aged 18-35 years) immediately before they engaged in a 3-D video game designed to assess multitasking performance. Participants were separated into three subgroups: real-sham (i.e., real tDCS in the first session, followed by sham tDCS in the second session 1 h later), sham-real (sham tDCS first session, real tDCS second session), and sham-sham (sham tDCS in both sessions). The real-sham group showed enhanced multitasking performance and decreased multitasking cost during the second session, compared to first session, suggesting delayed cognitive benefits of tDCS. Interestingly, performance benefits were observed only for multitasking and not on a single-task version of the game. No significant changes were found between the first and second sessions for either the sham-real or the sham-sham groups. These results suggest a causal role of left prefrontal cortex in facilitating the simultaneous performance of more than one task, or multitasking. Moreover, these findings reveal that anodal tDCS may have delayed benefits that reflect an enhanced rate of learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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.

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

PubMed

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.

Successful pharmacotherapy for the treatment of severe feeding aversion with mechanistic insights from cross-species neuronal remodeling

PubMed Central

Sharp, W G; Allen, A G; Stubbs, K H; Criado, K K; Sanders, R; McCracken, C E; Parsons, R G; Scahill, L; Gourley, S L

2017-01-01

Pediatric feeding disorders affect up to 5% of children, causing severe food intake problems that can result in serious medical and developmental outcomes. Behavioral intervention (BI) is effective in extinguishing feeding aversions, and also expert-dependent, time/labor-intensive and not well understood at a neurobiological level. Here we first conducted a double-blind, placebo-controlled trial comparing BI with BI plus d-cycloserine (DCS). DCS is a partial N-methyl-d-aspartate (NMDA) receptor agonist shown to augment extinction therapies in multiple anxiety disorders. We examined whether DCS enhanced extinction of feeding aversion in 15 children with avoidant/restrictive food intake disorder (ages 20–58 months). After five treatment days, BI improved feeding by 37%. By contrast, BI+DCS improved feeding by 76%. To gain insight into possible mechanisms of successful intervention, we next tested the neurobiological consequences of DCS in a murine model of feeding aversion and avoidance. In mice with conditioned food aversion, DCS enhanced avoidance extinction across a broad dose range. Confocal fluorescence microscopy and three-dimensional neuronal reconstruction indicated that DCS enlarged dendritic spine heads—the primary sites of excitatory plasticity in the brain—within the orbitofrontal prefrontal cortex, a sensory-cognition integration hub. DCS also increased phosphorylation of the plasticity-associated extracellular signal-regulated kinase 1/2. In summary, DCS successfully augments the extinction of food aversion in children and mice, an effect that may involve plasticity in the orbitofrontal cortex. These results warrant a larger-scale efficacy study of DCS for the treatment of pediatric feeding disorders and further investigations of neural mechanisms. PMID:28632204

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

PubMed Central

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

High definition-transcranial direct current stimulation changes older adults' subjective sleep and corresponding resting-state functional connectivity.

PubMed

Sheng, Jing; Xie, Chao; Fan, Dong-Qiong; Lei, Xu; Yu, Jing

2018-07-01

With advanced age, older adults show functional deterioration in sleep. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation, modulates individuals' behavioral performance in various cognitive domains. However, the modulation effect and neural mechanisms of tDCS on sleep, especially for the elderly population are not clear. Here, we aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) could modulate community-dwelling older adults' subjective sleep and whether these potential improvements are associated with the large-scale brain activity alterations recorded by functional magnetic resonance imaging. Thirty-one older adults were randomly allocated to the HD-tDCS group and the control group. HD-tDCS was applied for 25 min at 1.5 mA per day for two weeks. The anode electrode was placed over the left dorsolateral prefrontal cortex, surrounded by 4 cathodes at 7 cm radius. All participants completed sleep neuropsychological assessments and fMRI scans individually before and after intervention. Behaviorally, we observed a HD-tDCS-induced enhancement of older adults' sleep duration. On the aspect of the corresponding neural alterations, we observed that HD-tDCS decreased the functional connectivity between the default mode network (DMN) and subcortical network. More importantly, the decoupling connectivity of the DMN-subcortical network was correlated with the improvements of subjective sleep in the HD-tDCS group. Our findings add novel behavioral and neural evidences about tDCS-induced sleep improvement in community-dwelling older adults. With further development, tDCS may be used as an alternative treatment for sleep disorders and alleviate the dysfunction of brain networks induced by aging. Copyright © 2018 Elsevier B.V. All rights reserved.

Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning.

PubMed

Orlov, Natasza D; Tracy, Derek K; Joyce, Daniel; Patel, Shinal; Rodzinka-Pasko, Joanna; Dolan, Hayley; Hodsoll, John; Collier, Tracy; Rothwell, John; Shergill, Sukhwinder S

Schizophrenia is characterized by prominent cognitive deficits, impacting on memory and learning; these are strongly associated with the prefrontal cortex. To combine two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia. A double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task, indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions. 24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14-1.21; p = 0.044) and at day-56 (b = 0.71, 0.16-1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43-0.77; p = 0.058) was found. This is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study

PubMed Central

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP’s amplitude and NFR’s area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR’s area. High-frequency rTMS increased MEP’s amplitude and NFR’s area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes. PMID:29596524

Effects of repetitive transcranial magnetic stimulation and trans-spinal direct current stimulation associated with treadmill exercise in spinal cord and cortical excitability of healthy subjects: A triple-blind, randomized and sham-controlled study.

PubMed

Albuquerque, Plínio Luna; Campêlo, Mayara; Mendonça, Thyciane; Fontes, Luís Augusto Mendes; Brito, Rodrigo de Mattos; Monte-Silva, Katia

2018-01-01

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP's amplitude and NFR's area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR's area. High-frequency rTMS increased MEP's amplitude and NFR's area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-28

... Collection; Comment Request; NOAA Space- Based Data Collection System (DCS) Agreements AGENCY: National Oceanic and Atmospheric Administration (NOAA). ACTION: Notice. SUMMARY: The Department of Commerce, as... to Kay Metcalf, 301-817-4558 or [email protected]noaa.gov . SUPPLEMENTARY INFORMATION: I. Abstract This...

Dendritic Cells Induce a Subpopulation of IL-12Rβ2-Expressing Treg that Specifically Consumes IL-12 to Control Th1 Responses

PubMed Central

Sela, Uri; Park, Chae Gyu; Park, Andrew; Olds, Peter; Wang, Shu; Fischetti, Vincent A.

2016-01-01

Cytokines secreted from dendritic cells (DCs) play an important role in the regulation of T helper (Th) cell differentiation and activation into effector cells. Therefore, controlling cytokine secretion from DCs may potentially regulate Th differentiation/activation. DCs also induce de-novo generation of regulatory T cells (Treg) that modulate the immune response. In the current study we used the mixed leukocyte reaction (MLR) to investigate the effect of allospecific Treg on IL-12, TNFα and IL-6 secretion by DCs. Treg cells were found to markedly down-regulate IL-12 secretion from DCs following stimulation with TLR7/8 agonist. This down-regulation of IL-12 was neither due to a direct suppression of its production by the DCs nor a result of marked DC death. We found that IL-12 was rather actively consumed by Treg cells. IL-12 consumption was mediated by a subpopulation of IL-12Rβ2-expressing Treg cells and was dependent on MHC class-II expressed on dendritic cells. Furthermore, IL-12 consumption by Tregs increased their suppressive effect on T cell proliferation and Th1 activation. These results provide a new pathway of Th1 response regulation where IL-12 secreted by DCs is consumed by a sub-population of IL-12Rβ2-expressing Treg cells. Consumption of IL-12 by Tregs not only reduces the availability of IL-12 to Th effector cells but also enhances the Treg immunosuppressive effect. This DC-induced IL-12Rβ2-expressing Treg subpopulation may have a therapeutic advantage in suppressing Th1 mediated autoimmunity. PMID:26745371

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage: a double-blind randomized controlled trial.

PubMed

Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

2016-01-01

To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). A double-blind randomized controlled trial with one-week follow-up. Patients received five consecutive days of occupational therapy at home, combined with either anodal (n = 8) or sham (n = 7) tDCS. The primary outcome was ADL performance, which was assessed with the Jebsen-Taylor test (JTT). Both groups improved JTT over time (p < 0.01). The anodal group improved grip strength compared with the sham group from baseline to post-assessment (p = 0.025). However, this difference was attenuated at one-week follow-up. There was a non-significant tendency for greater improvement in JTT in the anodal group compared with the sham group, from baseline to post-assessment (p = 0.158). Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is a promising add-on intervention regarding training of upper limb motor impairment. It is well tolerated by patients and can easily be applied for home-based training. Larger studies with long-term follow-up are needed to further explore possible effects of tDCS in patients with ICH. Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is well tolerated by patients and can easily be applied for home-based rehabilitation.

Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study

PubMed Central

Palm, Ulrich; Keeser, Daniel; Hasan, Alkomiet; Kupka, Michael J.; Blautzik, Janusch; Sarubin, Nina; Kaymakanova, Filipa; Unger, Ina; Falkai, Peter; Meindl, Thomas; Ertl-Wagner, Birgit; Padberg, Frank

2016-01-01

Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (−36.1%) than after sham tDCS (−0.7%). PANSS sum scores decreased significantly more with active (−23.4%) than with sham stimulation (−2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia. PMID:27098066

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

PubMed

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.

Randomized, sham-controlled trial based on transcranial direct current stimulation and wrist robot-assisted integrated treatment on subacute stroke patients: Intermediate results.

PubMed

Mazzoleni, Stefano; Tran, Vi Do; Iardella, Laura; Dario, Paolo; Posteraro, Federico

2017-07-01

The main goal of this study is to analyse the effects of combined transcranial direct current stimulation (tDCS) and wrist robot-assisted therapy in subacute stroke patients. Twenty-four patients were included in this study and randomly assigned to the experimental (EG) or control group (CG). All participants performed wrist robot-assisted training a) in conjunction with tDCS (real stimulation for patients in EG) or b) without tDCS (sham stimulation for patients in CG). Clinical scales and kinematic parameters recorded by the robot were used for the assessment. Clinical outcome measures show a significant decrease in motor impairment after the treatment in both groups. Kinematic data show several significant improvements after the integrated therapy in both groups. However, no significant differences in both clinical outcome measures and kinematic parameters was found between two groups. The potential advantages of combined tDCS and wrist robot-assisted therapy in subacute stroke patients are still unclear.

A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells.

PubMed

Cook, Peter C; Owen, Heather; Deaton, Aimée M; Borger, Jessica G; Brown, Sheila L; Clouaire, Thomas; Jones, Gareth-Rhys; Jones, Lucy H; Lundie, Rachel J; Marley, Angela K; Morrison, Vicky L; Phythian-Adams, Alexander T; Wachter, Elisabeth; Webb, Lauren M; Sutherland, Tara E; Thomas, Graham D; Grainger, John R; Selfridge, Jim; McKenzie, Andrew N J; Allen, Judith E; Fagerholm, Susanna C; Maizels, Rick M; Ivens, Alasdair C; Bird, Adrian; MacDonald, Andrew S

2015-04-24

Dendritic cells (DCs) direct CD4(+) T-cell differentiation into diverse helper (Th) subsets that are required for protection against varied infections. However, the mechanisms used by DCs to promote Th2 responses, which are important both for immunity to helminth infection and in allergic disease, are currently poorly understood. We demonstrate a key role for the protein methyl-CpG-binding domain-2 (Mbd2), which links DNA methylation to repressive chromatin structure, in regulating expression of a range of genes that are associated with optimal DC activation and function. In the absence of Mbd2, DCs display reduced phenotypic activation and a markedly impaired capacity to initiate Th2 immunity against helminths or allergens. These data identify an epigenetic mechanism that is central to the activation of CD4(+) T-cell responses by DCs, particularly in Th2 settings, and reveal methyl-CpG-binding proteins and the genes under their control as possible therapeutic targets for type-2 inflammation.

Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

PubMed Central

Banchereau, Jacques; Zurawski, Sandra; Thompson-Snipes, LuAnn; Blanck, Jean-Philippe; Clayton, Sandra; Munk, Adiel; Cao, Yanying; Wang, Zhiqing; Khandelwal, Sunaina; Hu, Jiancheng; McCoy, William H.; Palucka, Karolina A.; Reiter, Yoram; Fremont, Daved H.; Zurawski, Gerard; Colonna, Marco; Shaw, Andrey S.; Klechevsky, Eynav

2012-01-01

Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8+ T cells compared with dermal CD14+ dendritic cells (DCs). Here we show that dermal CD14+ DCs instead prime a fraction of naïve CD8+ T cells into cells sharing the properties of type 2 cytokine-secreting CD8+ T cells (TC2). Differential expression of the CD8-antagonist receptors on dermal CD14+ DCs, the Ig-like transcript (ILT) inhibitory receptors, explains the difference between the two types of DCs. Inhibition of CD8 function on LCs inhibited cytotoxic T lymphocytes (CTLs) and enhanced TC2 generation. In addition, blocking ILT2 or ILT4 on dermal CD14+ DCs enhanced the generation of CTLs and inhibited TC2 cytokine production. Lastly, addition of soluble ILT2 and ILT4 receptors inhibited CTL priming by LCs. Thus, ILT receptor expression explains the polarization of CD8+ T-cell responses by LCs vs. dermal CD14+ DCs. PMID:23112154

System Control for the Transitional DCS.

DTIC Science & Technology

1979-05-01

Avenue I . NUMBER OF PAGES Reston, VA 22090 300 14. MONITORING AGENCY NAME & ADDRESS(if different from Controlling Office) IS. SECURITY CLASS. (of this...adjusting the routing in the AUTOVON Network. DD FORMj 73 1473 EOITION OF I NOV 65 IS OBSOLETE YV_, UNCLASSIFIED [ L.j 29.? .’ SECURITY CLASSIFICATION OF THIS...PAGE ("en Data Entered) SECURIT’, 1.LASSIPrICATIO04 OP THIS PAGE(Wbmn Deta.Entered) SECURITY CLASIIPICATIOM OF U* PAGE(nem" Data Entoewl I I I SYSTEM

Social support and its interrelationships with demand-control model factors on presenteeism and absenteeism in Japanese civil servants.

PubMed

Saijo, Yasuaki; Yoshioka, Eiji; Nakagi, Yoshihiko; Kawanishi, Yasuyuki; Hanley, Sharon J B; Yoshida, Takahiko

2017-08-01

To elucidate the impact of social support and its interrelations with other demand-control-support (DCS) model factors on presenteeism and absenteeism, and to determine which DCS factors were most influential. Questionnaires from 2535 local government employees were analyzed. The Brief Job Stress Questionnaire (BJSQ) was used to assess DCS factors including job demand, job control, and social support from supervisors and coworkers. The Stanford Presenteeism Scale 13-item version (SPS-13) was used to evaluate both absenteeism (absent days) and presenteeism. For the latter, the Work Impairment Score (WIS) and the Work Output Score (WOS) were also used. Possible confounder-adjusted logistic and negative binomial regression analyses were performed to obtain odds ratios (ORs) for WIS and WOS and relative risks (RRs) for absenteeism according to DCS factors. Higher job control had a significantly protective effect on higher WIS in both males and females and a lower WOS in males. Based on a point estimate of an OR per 1 standard deviation change of each DCS factor, job control had the strongest effect on higher WIS in both males and females and a lower WOS in males. Higher job demand resulted in significantly higher ORs for both male and female WIS, and a lower WOS in females. Support from supervisors had a significantly protective effect on higher WIS in females and a lower WOS in males. Support from coworkers had a significantly protective effect on higher WIS in males. Higher support from coworkers had a significantly protective effect on absenteeism among both males and females, and higher job control had a significantly protective effect in females. The combination of high job strain and low support from supervisors had a significantly worsening effect, except for absenteeism in females. High job strain and low support from coworkers had a significantly worsening effect except for WOS in males. The results suggest job control was the DCS factor most related to presenteeism. Higher support from supervisors and coworkers had a protective effect on presenteeism, and higher job demand had a worsening effect. Higher support from coworkers had a protective effect on absenteeism among both males and females. Interventions should focus on improving job control as a possible countermeasure to presenteeism, and encouraging support from coworkers as a possible countermeasure to absenteeism.

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

PubMed

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.

Effects of an NMDA antagonist on the auditory mismatch negativity response to transcranial direct current stimulation.

PubMed

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

2017-05-01

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a weak constant current to alter cortical excitability and activity temporarily. tDCS-induced increases in neuronal excitability and performance improvements have been observed following anodal stimulation of brain regions associated with visual and motor functions, but relatively little research has been conducted with respect to auditory processing. Recently, pilot study results indicate that anodal tDCS can increase auditory deviance detection, whereas cathodal tDCS decreases auditory processing, as measured by a brain-based event-related potential (ERP), mismatch negativity (MMN). As evidence has shown that tDCS lasting effects may be dependent on N-methyl-D-aspartate (NMDA) receptor activity, the current study investigated the use of dextromethorphan (DMO), an NMDA antagonist, to assess possible modulation of tDCS's effects on both MMN and working memory performance. The study, conducted in 12 healthy volunteers, involved four laboratory test sessions within a randomised, placebo and sham-controlled crossover design that compared pre- and post-anodal tDCS over the auditory cortex (2 mA for 20 minutes to excite cortical activity temporarily and locally) and sham stimulation (i.e. device is turned off) during both DMO (50 mL) and placebo administration. Anodal tDCS increased MMN amplitudes with placebo administration. Significant increases were not seen with sham stimulation or with anodal stimulation during DMO administration. With sham stimulation (i.e. no stimulation), DMO decreased MMN amplitudes. Findings from this study contribute to the understanding of underlying neurobiological mechanisms mediating tDCS sensory and memory improvements.

Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

PubMed Central

Behler, Friederike; Maus, Regina; Bohling, Jennifer; Knippenberg, Sarah; Kirchhof, Gabriele; Nagata, Masahiro; Jonigk, Danny; Izykowski, Nicole; Mägel, Lavinia; Welte, Tobias; Yamasaki, Sho

2014-01-01

The macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6′,6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously with Mycobacterium bovis BCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC+/DTR mice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenic M. bovis BCG infection in mice. PMID:25332121

High Precision Motion Control System for the Two-Stage Light Gas Gun at the Dynamic Compression Sector

NASA Astrophysics Data System (ADS)

Zdanowicz, E.; Guarino, V.; Konrad, C.; Williams, B.; Capatina, D.; D'Amico, K.; Arganbright, N.; Zimmerman, K.; Turneaure, S.; Gupta, Y. M.

2017-06-01

The Dynamic Compression Sector (DCS) at the Advanced Photon Source (APS), located at Argonne National Laboratory (ANL), has a diverse set of dynamic compression drivers to obtain time resolved x-ray data in single event, dynamic compression experiments. Because the APS x-ray beam direction is fixed, each driver at DCS must have the capability to move through a large range of linear and angular motions with high precision to accommodate a wide variety of scientific needs. Particularly challenging was the design and implementation of the motion control system for the two-stage light gas gun, which rests on a 26' long structure and weighs over 2 tons. The target must be precisely positioned in the x-ray beam while remaining perpendicular to the gun barrel axis to ensure one-dimensional loading of samples. To accommodate these requirements, the entire structure can pivot through 60° of angular motion and move 10's of inches along four independent linear directions with 0.01° and 10 μm resolution, respectively. This presentation will provide details of how this system was constructed, how it is controlled, and provide examples of the wide range of x-ray/sample geometries that can be accommodated. Work supported by DOE/NNSA.

Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

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

Fukuyama, Yoshiko; Tokuhara, Daisuke; Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639

Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FLmore » activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.« less

TNF-α and Tumor Lysate Promote the Maturation of Dendritic Cells for Immunotherapy for Advanced Malignant Bone and Soft Tissue Tumors

PubMed Central

Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takata, Munetomo; Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Kimura, Hiroaki; Igarashi, Kentaro; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

2012-01-01

Background Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli. Methods Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-γ and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy. Results Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL-12 showed significant elevation at one and three months after DC-based immunotherapy. Conclusions Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors. PMID:23300824

Toxoplasma gondii infection shifts dendritic cells into an amoeboid rapid migration mode encompassing podosome dissolution, secretion of TIMP-1, and reduced proteolysis of extracellular matrix.

PubMed

Ólafsson, Einar B; Varas-Godoy, Manuel; Barragan, Antonio

2018-03-01

Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a "Trojan horse" mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T. gondii exhibited dependency on metalloproteinase activity for hypermotility and transmigration but, strikingly, also dramatically reduced pericellular proteolysis. Toxoplasma-challenged DCs up-regulated expression and secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) and their supernatants impaired matrix degradation by naïve DCs and by-stander DCs dose dependently. Gene silencing of TIMP-1 by short hairpin RNA restored matrix degradation activity in Toxoplasma-infected DCs. Additionally, dissolution of podosome structures in parasitised DCs coincided with abrogated matrix degradation. Toxoplasma lysates inhibited pericellular proteolysis in a MyD88-dependent fashion whereas abrogated proteolysis persevered in Toxoplasma-infected MyD88-deficient DCs. This indicated that both TLR/MyD88-dependent and TLR/MyD88-independent signalling pathways mediated podosome dissolution and the abrogated matrix degradation. We report that increased TIMP-1 secretion and cytoskeletal rearrangements encompassing podosome dissolution are features of Toxoplasma-induced hypermigration of DCs with an impact on matrix degradation. Jointly, the data highlight how an obligate intracellular parasite orchestrates key regulatory cellular processes consistent with non-proteolytic amoeboid migration of the vehicle cells that facilitate its dissemination. © 2017 John Wiley & Sons Ltd.

Effect of Anodal and Cathodal Transcranial Direct Current Stimulation on DLPFC on Modulation of Inhibitory Control in ADHD.

PubMed

Soltaninejad, Zahra; Nejati, Vahid; Ekhtiari, Hamed

2015-12-20

The purpose of this study was to improve the inhibitory control functions through transcranial direct current stimulation (tDCS) in adolescents with ADHD symptoms. Twenty high school students with ADHD symptoms participated in this single-blinded, crossover, sham-controlled study. All the participants were tested during the application of Stroop and Go/No-Go tasks that is used to measure inhibitory control, using 1.5 mA of tDCS for 15 min over the left dorsolateral prefrontal cortex (DLPFC). Anodal stimulation on left DLPFC had no effect on interference inhibition during the Stroop task and increased the proportion of correct responses in the "Go stage" of the Go/No-Go test compared with sham condition. Cathodal stimulation on the left DLPFC increased the inhibition accuracy in the inhibition stage during Go/No-Go task in comparison with sham. tDCS over the left DLPFC of adolescents who suffer from ADHD symptoms can improve inhibitory control in prepotent response inhibition. © The Author(s) 2015.

Combination of a short cognitive training and tDCS to enhance visuospatial skills: A comparison between online and offline neuromodulation.

PubMed

Oldrati, Viola; Colombo, Barbara; Antonietti, Alessandro

2018-01-01

Visuospatial skills can be enhanced thanks to specific intervention programs, but the additional benefits of neuromodulation on these skills have not been fully investigated yet, although transcranial direct current stimulation (tDCS) has demonstrated to boost the effects of cognitive trainings. When combining cognitive intervention with neuromodulation, the time-window of tDCS application in relation to task execution has to be taken into account since it has been shown to affect stimulation outcomes. The aim of the present experiment was to investigate the influence of tDCS in enhancing the effects of a training for visuospatial skills. We hypothesized that tDCS applied during training execution (online) would improve the cognitive performance at a larger extent than tDCS applied before training execution (offline). Participants received anodal tDCS over the dorsolateral prefrontal cortex during (online) or before (offline) the completion of the training. A control sham condition was included. Visuospatial abilities were measured 24 h before (day 1, pre-test) and 24 h after (day 3, post-test) the stimulation and training session (day 2). tDCS enhanced gains for mental folding performance when applied during the execution of the training (online). Participants' mental rotation and mental folding performance improved from pre-test to post-test regardless of the stimulation condition. However participants in the online tDCS condition showed the largest improvement in mental folding performance. Findings indicate that tDCS enhanced the effects of the training when applied during its execution, showing cumulative positive aftereffects on visuospatial performance 24 h after the stimulation session. The time-dependent effect points out the importance of the time-window of tDCS application in influencing behavior when combined with cognitive programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Despite Increased Type 1 IFN, Autoimmune Nonobese Diabetic Mice Display Impaired Dendritic Cell Response to CpG and Decreased Nuclear Localization of IFN-Activated STAT1.

PubMed

Rahman, M Jubayer; Rahir, Gwendoline; Dong, Matthew B; Zhao, Yongge; Rodrigues, Kameron B; Hotta-Iwamura, Chie; Chen, Ye; Guerrero, Alan; Tarbell, Kristin V

2016-03-01

Innate immune signals help break self-tolerance to initiate autoimmune diseases such as type 1 diabetes, but innate contributions to subsequent regulation of disease progression are less clear. Most studies have measured in vitro innate responses of GM-CSF dendritic cells (DCs) that are functionally distinct from conventional DCs (cDCs) and do not reflect in vivo DC subsets. To determine whether autoimmune NOD mice have alterations in type 1 IFN innate responsiveness, we compared cDCs from prediabetic NOD and control C57BL/6 (B6) mice stimulated in vivo with the TLR9 ligand CpG, a strong type 1 IFN inducer. In response to CpG, NOD mice produce more type 1 IFN and express higher levels of CD40, and NOD monocyte DCs make more TNF. However, the overall CpG-induced transcriptional response is muted in NOD cDCs. Of relevance the costimulatory proteins CD80/CD86, signals needed for regulatory T cell homeostasis, are upregulated less on NOD cDCs. Interestingly, NOD Rag1(-/-) mice also display a defect in CpG-induced CD86 upregulation compared with B6 Rag1(-/-), indicating this particular innate alteration precedes adaptive autoimmunity. The impaired response in NOD DCs is likely downstream of the IFN-α/β receptor because DCs from NOD and B6 mice show similar CpG-induced CD86 levels when anti-IFN-α/β receptor Ab is added. IFN-α-induced nuclear localization of activated STAT1 is markedly reduced in NOD CD11c(+) cells, consistent with lower type 1 IFN responsiveness. In conclusion, NOD DCs display altered innate responses characterized by enhanced type 1 IFN and activation of monocyte-derived DCs but diminished cDC type 1 IFN response.

Chitosan as an adjuvant-like substrate for dendritic cell culture to enhance antitumor effects.

PubMed

Lin, Yong-Chong; Lou, Pei-Jen; Young, Tai-Horng

2014-10-01

To induce monocyte differentiation into dendritic cells (DCs) is the essential protocol for the DC-mediated cancer immunotherapy. In this study, monocytes isolated from mouse bone marrow were cultured on chitosan substrate to evaluate the effect of the chitosan culture system on the induction and tumor protection of DCs. Compared to tissue culture polystyrene (TCPS), the chitosan culture system could enhance monocyte aggregation and detachment with increased MTT reduction activity and expression of DC marker CD11c and LPS co-receptor CD14. Moreover, compared to TCPS, chitosan could enhance lipopolysaccharides (LPS)-stimulated DCs to secrete higher amount of IL-12. More importantly, vaccination of tumor lysate-pulsed DCs harvested from chitosan could increase cytotoxic T-lymphocyte (CTL) activity and showed significantly enhanced anti-tumor effect than those from TCPS. Therefore, the current study demonstrated that a protocol to culture DCs on a less-adherent chitosan substrate followed by treatment with tumor lysate has the potential in future DC-based vaccine application. Copyright © 2014 Elsevier Ltd. All rights reserved.

Need for speed: evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine.

PubMed

Chasson, Gregory S; Buhlmann, Ulrike; Tolin, David F; Rao, Sowmya R; Reese, Hannah E; Rowley, Theresa; Welsh, Kaitlyn S; Wilhelm, Sabine

2010-07-01

Evidence suggests that the antibiotic d-cycloserine (DCS) enhances the treatment effects of exposure and response prevention (ERP) for Obsessive-Compulsive Disorder (OCD). Further, evidence suggests that the effects of DCS diminish partway through treatment, but it is unclear to what extent. In an effort to evaluate these issues, the current study re-analyzes data from a 10-session randomized controlled trial of ERP+DCS versus ERP+placebo in a sample of 22 adults with OCD. We analyzed repeated-measures mixed models with random slopes and intercepts across different intervals: sessions 1-10, 1-5, and 6-10. The results indicate that the course of ERP was 2.3 times faster over the full 10 sessions for the DCS compared to the placebo group, and nearly six times quicker in the first half of ERP. Further interpretation of the results suggests that DCS does not amplify the effects of ERP, but instead initiates treatment effects sooner in treatment. In addition, DCS does not necessarily lose its effect over repeated use, but instead may exhaust its maximum utility after effectively jump-starting ERP. Ultimately, DCS may provide a means for curtailing treatment costs, decreasing treatment dropout and refusal rates, and enhancing access to care. Copyright 2010 Elsevier Ltd. All rights reserved.

Transcranial direct current stimulation in children and adolescents: a comprehensive review.

PubMed

Palm, Ulrich; Segmiller, Felix M; Epple, Ann Natascha; Freisleder, Franz-Joseph; Koutsouleris, Nikolaos; Schulte-Körne, Gerd; Padberg, Frank

2016-10-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that has shown promising results in various neuropsychiatric disorders in adults. This review addresses the therapeutic use of tDCS in children and adolescents including safety, ethical, and legal considerations. There are several studies addressing the dosage of tDCS in children and adolescents by computational modeling of electric fields in the pediatric brain. Results suggest halving the amperage used in adults to obtain the same peak electric fields, however, there are some studies reporting on the safe application of tDCS with standard adult parameters in children (2 mA; 20-30 min). There are several randomized placebo controlled trials suggesting beneficial effects of tDCS for the treatment of cerebral palsy. For dystonia there are mixed data. Some studies suggest efficacy of tDCS for the treatment of refractory epilepsy, and for the improvement of attention deficit/hyperactivity disorder and autism. Interestingly, there is a lack of data for the treatment of childhood and adolescent psychiatric disorders, i.e., childhood onset schizophrenia and affective disorders. Overall, tDCS seems to be safe in pediatric population. More studies are needed to confirm the preliminary encouraging results; however, ethical deliberation has to be weighed carefully for every single case.

Mechanistic studies of systemic immune responses induced by laser-nanotechnology

NASA Astrophysics Data System (ADS)

Chen, Wei R.; Zhou, Feifan; Henderson, Brock; Vasquez, Bailey; Liu, Hong; Hode, Tomas; Nordquist, Robert E.

2014-02-01

With the help of the specific absorption spectrum of carbon nanotubes, we achieved selective photothermal tumor cell destruction, particularly using a near-infrared laser to reduce potential damage to untargeted tissues. Combined with immunological stimulation, using a novel adjuvant, we also observed the anti-tumor immune responses when treating animal tumors using the laser-nano treatment. In fact, the local application of laser-nano-immunotherapy appeared to result in a systemic curative effect. In our mechanistic study, we found that the laser-nano-immuno treatment can activate antigen-presenting cells, such as dendritic cells (DCs). More importantly, the uptake and presentation of antigens by these antigen presenting cells were significantly enhanced, as shown by the strong binding of tumor cells and DCs as well as the proliferation of T cells caused by the DCs after the DCs had been incubated with laser-nano-immuno treated tumors. These cellular observations provide evidence that a systemic anti-tumor immune response was induced by the combination of laser and nanotechnology.

Does Otosclerosis Affect Dark and Transitional Cells in the Human Vestibular Labyrinth?

PubMed

Kaya, Serdar; Paparella, Michael M; Cureoglu, Sebahattin

2017-02-01

The density of vestibular dark cells (DCs) and vestibular transitional cells (TCs) can be quantitatively decreased in human temporal bones with otosclerosis. Previous reports have shown that otosclerosis can lead to vestibular symptoms. We examined 61 human temporal bone specimens from 52 deceased donors with otosclerosis group-with and without endosteal involvement (EI), and with and without endolymphatic hydrops (EH)-versus 25 specimens from 18 age-matched controls. Using light microscopy, we evaluated the nonsensory epithelium of the lateral semicircular canal (LSC) and posterior semicircular canal (PSC) of the human vestibular labyrinth, focusing on the density of DCs and TCs. In both the LSC and the PSC, as compared with the control group, the mean density of DCs significantly decreased in the EI (+) group, in the EI (+) and EH (+) subgroup, and in the EI (+) and EH (-) subgroup (p < 0.05). In addition, we found a significant difference in the mean density of DCs between the EI (+) group and the EI (-) group in the LSC and in the PSC (p < 0.05). But we found no significant difference in the mean density of TCs in any of the otosclerosis groups or subgroups as compared with the control group (p > 0.05). We found a decrease in the density of DCs associated with EI in human temporal bone specimens with otosclerosis, regardless of the presence of EH. This decrease might cause damage in ion and water transportation, leading to vestibular symptoms.

Does Otosclerosis Affect Dark and Transitional Cells in the Human Vestibular Labyrinth?

PubMed Central

Kaya, Serdar; Paparella, Michael M.; Cureoglu, Sebahattin

2016-01-01

Hypothesis The density of vestibular dark cells (DCs) and vestibular transitional cells (TCs) can be quantitatively decreased in human temporal bones with otosclerosis. Background Previous reports have shown that otosclerosis can lead to vestibular symptoms. Methods We examined 61 human temporal bone specimens from 52 deceased donors with otosclerosis group—with and without endosteal involvement (EI), and with and without endolymphatic hydrops (EH)—vs. 25 specimens from 18 age-matched controls. Using light microscopy, we evaluated the nonsensory epithelium of the lateral semicircular canal (LSC) and posterior semicircular canal (PSC) of the human vestibular labyrinth, focusing on the density of DCs and TCs. Results In both the LSC and the PSC, as compared with the control group, the mean density of DCs significantly decreased in the EI (+) group, in the EI (+) and EH (+) subgroup, and in the EI (+) and EH (−) subgroup (P < 0.05). In addition, we found a significant difference in the mean density of DCs between the EI (+) group and the EI (−) group in the LSC and in the PSC (P < 0.05). But we found no significant difference in the mean density of TCs in any of the otosclerosis groups or subgroups as compared with the control group (P > 0.05). Conclusion We found a decrease in the density of DCs associated with EI in human temporal bone specimens with otosclerosis, regardless of the presence of EH. This decrease might cause damage in ion and water transportation, leading to vestibular symptoms. PMID:27851656

DCS-Neural-Network Program for Aircraft Control and Testing

NASA Technical Reports Server (NTRS)

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.

Joint Optimization of Distribution Network Design and Two-Echelon Inventory Control with Stochastic Demand and CO2 Emission Tax Charges.

PubMed

Li, Shuangyan; Li, Xialian; Zhang, Dezhi; Zhou, Lingyun

2017-01-01

This study develops an optimization model to integrate facility location and inventory control for a three-level distribution network consisting of a supplier, multiple distribution centers (DCs), and multiple retailers. The integrated model addressed in this study simultaneously determines three types of decisions: (1) facility location (optimal number, location, and size of DCs); (2) allocation (assignment of suppliers to located DCs and retailers to located DCs, and corresponding optimal transport mode choices); and (3) inventory control decisions on order quantities, reorder points, and amount of safety stock at each retailer and opened DC. A mixed-integer programming model is presented, which considers the carbon emission taxes, multiple transport modes, stochastic demand, and replenishment lead time. The goal is to minimize the total cost, which covers the fixed costs of logistics facilities, inventory, transportation, and CO2 emission tax charges. The aforementioned optimal model was solved using commercial software LINGO 11. A numerical example is provided to illustrate the applications of the proposed model. The findings show that carbon emission taxes can significantly affect the supply chain structure, inventory level, and carbon emission reduction levels. The delay rate directly affects the replenishment decision of a retailer.

Regulation of Ion Transport in the Intestine by Free Fatty Acid Receptor 2 and 3: Possible Involvement of the Diffuse Chemosensory System

PubMed Central

Kuwahara, Atsukazu; Kuwahara, Yuko; Inui, Toshio; Marunaka, Yoshinori

2018-01-01

The diffuse chemosensory system (DCS) is well developed in the apparatuses of endodermal origin like gastrointestinal (GI) tract. The primary function of the GI tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal contents for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in the luminal content. The chemosensory cells in the GI tract belong to the DCS which consists of enteroendocrine and related cells. These cells initiate various important local and remote reflexes. Although neural and hormonal involvements in ion transport in the GI tract are well documented, involvement of the DCS in the regulation of intestinal ion transport is much less understood. Since activation of luminal chemosensory receptors is a primary signal that elicits changes in intestinal ion transport and motility and failure of the system causes dysfunctions in host homeostasis, as well as functional GI disorders, study of the regulation of GI function by the DCS has become increasingly important. This review discusses the role of the DCS in epithelial ion transport, with particular emphasis on the involvement of free fatty acid receptor 2 (FFA2) and free fatty acid receptor 3 (FFA3). PMID:29510573

Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement

PubMed Central

Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

2016-01-01

Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition. PMID:26902664

Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

PubMed

Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

2016-02-23

Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

Alternative strategy for visceral leishmaniosis control: HisAK70-Salmonella Choleraesuis-pulsed dendritic cells.

PubMed

Domínguez-Bernal, Gustavo; Martínez-Rodrigo, Abel; Mas, Alicia; Blanco, M Mar; Orden, José A; De La Fuente, Ricardo; Carrión, Javier

2017-10-01

Here, we describe a novel approach that exploits an attenuated mutant of Salmonella enterica serovar Choleraesuis as carrier to deliver a plasmid encoding protein HisAK70. Subsequently, dendritic cells (DCs) were pulsed with this vaccine vector. The aim of this study was to evaluate the effectiveness of the prepared HisAK70-S. Choleraesuis-pulsed DCs (HisAK70-SAL DCs) against visceral leishmaniosis (VL). In our ex vivo model of infection, the prepared formulations could decrease parasite growth by up to 80% by augmenting the production of IL-12p40 and by reducing arginase activity (ARG). Also, BALB/c mice when immunised with this formulation showed significant reduction in parasite burden in both spleen (20% of reduction) and liver (75% of reduction). The balance of the immune ratios IFN-γ/IL-10, TNF-α/IL-10, and IgG2a/IgG1 reflected the acquisition of an improved resistant phenotype in HisAK70-SAL DCs vaccinated mice compared to control mice. Our results suggest that HisAK70-SAL DCs could be a promising alternative approach for vaccine delivery that has the potential to fight Leishmania infantum (L. infantum) infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of repeated altitude exposures on the incidence of decompression sickness

NASA Technical Reports Server (NTRS)

Pilmanis, Andrew A.; Webb, James T.; Kannan, Nandini; Balldin, Ulf

2002-01-01

INTRODUCTION: Repeated altitude exposures in a single day occur during special operations parachute training, hypobaric chamber training, unpressurized flight, and extravehicular space activity. Inconsistent and contradictory information exists regarding the risk of decompression sickness (DCS) during such hypobaric exposures. HYPOTHESIS: We hypothesized that four short exposures to altitude with and without ground intervals would result in a lower incidence of DCS than a single exposure of equal duration. METHODS: The 32 subjects were exposed to 3 different hypobaric exposures--condition A: 2 h continuous exposure (control); condition B: four 30-min exposures with descent/ascent but no ground interval between the exposures; condition C: four 30-min exposures with descent/ascent and 60 min of ground interval breathing air between exposures. All exposures were to 25,000 ft with 100% oxygen breathing. Subjects were observed for symptoms of DCS, and precordial monitoring of venous gas emboli (VGE) was accomplished with a SONOS 1000 echo-imaging system. RESULTS: DCS occurred in 19 subjects during A (mean onset 70+/-29 min), 7 subjects in B (60+/-34 min), and 2 subjects in C (40+/-18 min). There was a significant difference in DCS incidence between B and A (p = 0.0015) and C and A (p = 0.0002), but no significant difference between B and C. There were 28 cases of VGE in A (mean onset 30+/-23 min), 21 in B (41+/-35 min), and 21 in C (41+/-32 min) with a significant onset curve difference between B and A and between C and A, but not between B and C. Exposure A resulted in four cases of serious respiratory/neurological symptoms, while B had one and C had none. All symptoms resolved during recompression to ground level. CONCLUSION: Data indicate that repeated simulated altitude exposures to 25,000 ft significantly reduce DCS and VGE incidence compared with a single continuous altitude exposure.

Combined brain Fe, Cu, Zn and neurometabolite analysis - a new methodology for unraveling the efficacy of transcranial direct current stimulation (tDCS) in appetite control.

PubMed

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.

78 FR 68816 - Proposed Information Collection; Comment Request; NOAA Space-Based Data Collection System (DCS...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... Collection; Comment Request; NOAA Space- Based Data Collection System (DCS) Agreements AGENCY: National Oceanic and Atmospheric Administration (NOAA). ACTION: Notice. SUMMARY: The Department of Commerce, as... directed to Scott Rogerson, 301-817-4543 or [email protected]noaa.gov ; or Kay Metcalf, 301-817-4558 or kay...

Does Transcranial Direct Current Stimulation Combined with Peripheral Electrical Stimulation Have an Additive Effect in the Control of Hip Joint Osteonecrosis Pain Associated with Sickle Cell Disease? A Protocol for a One-Session Double Blind, Block-Randomized Clinical Trial.

PubMed

Lopes, Tiago da Silva; Silva, Wellington Dos Santos; Ribeiro, Sânzia B; Figueiredo, Camila A; Campbell, Fernanda Q; Daltro, Gildasio de Cerqueira; Valenzuela, Antônio; Montoya, Pedro; Lucena, Rita de C S; Baptista, Abrahão F

2017-01-01

Chronic pain in Sickle Cell Disease (SCD) is probably related to maladaptive plasticity of brain areas involved in nociceptive processing. Transcranial Direct Current Stimulation (tDCS) and Peripheral Electrical Stimulation (PES) can modulate cortical excitability and help to control chronic pain. Studies have shown that combined use of tDCS and PES has additive effects. However, to date, no study investigated additive effects of these neuromodulatory techniques on chronic pain in patients with SCD. This protocol describes a study aiming to assess whether combined use of tDCS and PES more effectively alleviate pain in patients with SCD compared to single use of each technique. The study consists of a one-session double blind, block-randomized clinical trial (NCT02813629) in which 128 participants with SCD and femoral osteonecrosis will be enrolled. Stepwise procedures will occur on two independent days. On day 1, participants will be screened for eligibility criteria. On day 2, data collection will occur in four stages: sample characterization, baseline assessment, intervention, and post-intervention assessment. These procedures will last ~5 h. Participants will be divided into two groups according to homozygous for S allele (HbSS) ( n = 64) and heterozygous for S and C alleles (HbSC) ( n = 64) genotypes. Participants in each group will be randomly assigned, equally, to one of the following interventions: (1) active tDCS + active PES; (2) active tDCS + sham PES; (3) sham tDCS + active PES; and (4) sham tDCS + sham PES. Active tDCS intervention will consist of 20 min 2 mA anodic stimulation over the primary motor cortex contralateral to the most painful hip. Active PES intervention will consist of 30 min sensory electrical stimulation at 100 Hz over the most painful hip. The main study outcome will be pain intensity, measured by a Visual Analogue Scale. In addition, electroencephalographic power density, cortical maps of the gluteus maximus muscle elicited by Transcranial Magnetic Stimulation (TMS), serum levels of Brain-derived Neurotrophic Factor (BDNF), and Tumor Necrosis Factor (TNF) will be assessed as secondary outcomes. Data will be analyzed using ANOVA of repeated measures, controlling for confounding variables.

Day care PNL using 'Santosh-PGI hemostatic seal' versus standard PNL: A randomized controlled study.

PubMed

Kumar, Santosh; Singh, Shivanshu; Singh, Prashant; Singh, Shrawan Kumar

2016-01-01

To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission.

Day care PNL using ‘Santosh-PGI hemostatic seal’ versus standard PNL: A randomized controlled study

PubMed Central

Singh, Shivanshu; Singh, Prashant; Singh, Shrawan Kumar

2016-01-01

Introduction To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. Material and methods It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. Results A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). Conclusions Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission. PMID:27551557

Gender not a factor for altitude decompression sickness risk

NASA Technical Reports Server (NTRS)

Webb, James T.; Kannan, Nandini; Pilmanis, Andrew A.

2003-01-01

INTRODUCTION: Early, retrospective reports of the incidence of altitude decompression sickness (DCS) during altitude chamber training exposures indicated that women were more susceptible than men. We hypothesized that a controlled, prospective study would show no significant difference. METHODS: We conducted 25 altitude chamber decompression exposure profiles. A total of 291 human subjects, 197 men and 94 women, underwent 961 exposures to simulated altitude for up to 8 h, using zero to 4 h of preoxygenation. Throughout the exposures, subjects breathed 100% oxygen, rested or performed mild or strenuous exercise, and were monitored for precordial venous gas emboli (VGE) and DCS symptoms. RESULTS: No significant differences in DCS incidence were observed between men (49.5%) and women (45.3%). However, VGE occurred at significantly higher rates among men than women under the same exposure conditions, 69.3% and 55.0% respectively. Women using hormonal contraception showed significantly greater susceptibility to DCS than those not using hormonal contraception during the latter two weeks of the menstrual cycle. Significantly higher DCS incidence was observed in the heaviest men, in women with the highest body fat, and in subjects with the highest body mass indices and lowest levels of fitness. CONCLUSION: No differences in altitude DCS incidence were observed between the sexes under our test conditions, although men developed VGE more often than women. Age and height showed no significant influence on DCS incidence, but persons of either sex with higher body mass index and lower physical fitness developed DCS more frequently.

MIF Promotes Classical Activation and Conversion of Inflammatory Ly6Chigh Monocytes into TipDCs during Murine Toxoplasmosis

PubMed Central

Ruiz-Rosado, Juan de Dios; Olguín, Jonadab E.; Juárez-Avelar, Imelda; Saavedra, Rafael; Terrazas, Luis I.; Robledo-Avila, Frank H.; Vazquez-Mendoza, Alicia; Fernández, Jacquelina; Satoskar, Abhay R.; Partida-Sánchez, Santiago; Rodriguez-Sosa, Miriam

2016-01-01

Macrophage migration inhibitory factor (MIF) mediates immunity against Toxoplasma gondii infection by inducing inflammatory cytokines required to control the parasite replication. However, the role of this inflammatory mediator in the cell-mediated immune response against this infection is still poorly understood. Here, we used T. gondii-infected WT and Mif −/− mice to analyze the role of MIF in the maturation of CD11b+ and CD8α + dendritic cells (DCs). We found that MIF promotes maturation of CD11b+ but not CD8α + DCs, by inducing IL-12p70 production and CD86 expression. Infected Mif −/− mice showed significantly lower numbers of TNF and inducible nitric oxide synthase- (iNOS-) producing DCs (TipDCs) compared to infected WT mice. The adoptive transfer of Ly6Chigh monocytes into infected WT or Mif −/− mice demonstrated that MIF participates in the differentiation of Ly6Chigh monocytes into TipDCs. In addition, infected Mif −/− mice display a lower percentage of IFN-γ-producing natural killer (NK) cells compared to WT mice, which is associated with reducing numbers of TipDCs in Mif −/− mice. Furthermore, administration of recombinant MIF (rMIF) into T. gondii-infected Mif −/− mice restored the numbers of TipDCs and reversed the susceptible phenotype of Mif −/− mice. Collectively, these results demonstrate an important role for MIF inducing cell-mediated immunity to T. gondii infection. PMID:27057101

Brain-computer interface training combined with transcranial direct current stimulation in patients with chronic severe hemiparesis: Proof of concept study.

PubMed

Kasashima-Shindo, Yuko; Fujiwara, Toshiyuki; Ushiba, Junichi; Matsushika, Yayoi; Kamatani, Daiki; Oto, Misa; Ono, Takashi; Nishimoto, Atsuko; Shindo, Keiichiro; Kawakami, Michiyuki; Tsuji, Tetsuya; Liu, Meigen

2015-04-01

Brain-computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain-computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain-computer interface training in patients with severe hemiparesis. Eighteen patients with chronic stroke. A non-randomized controlled study. Subjects were divided between a brain-computer interface group and a tDCS- brain-computer interface group and participated in a 10-day brain-computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain-computer interface group received anodal tDCS before brain-computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention. Event-related desynchronization was significantly increased in the tDCS- brain-computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCS-brain-computer interface group. Anodal tDCS can be a conditioning tool for brain-computer interface training in patients with severe hemiparetic stroke.

Transcranial Direct Current Stimulation Modulates Neuronal Networks in Attention Deficit Hyperactivity Disorder.

PubMed

Sotnikova, Anna; Soff, Cornelia; Tagliazucchi, Enzo; Becker, Katja; Siniatchkin, Michael

2017-09-01

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been repeatedly shown to improve working memory (WM). Since patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in WM, the modulation of prefrontal activity with tDCS in ADHD patients may increase their WM performance as well as improve the activation and connectivity of the WM network. In the present study, this hypothesis was tested using a double-blind sham-controlled experimental design. After randomization, sixteen adolescents with ADHD underwent either anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC, 1 mA, 20 min) or sham stimulation with simultaneous fMRI during n-back WM task. Both in one-back and two-back conditions, tDCS led to a greater activation (compared with sham stimulation) of the left DLPFC (under the electrode), left premotor cortex, left supplementary motor cortex, and precuneus. The effects of tDCS were long-lasting and influenced resting state functional connectivity even 20 min after the stimulation, with patterns of strengthened DLPFC connectivity after tDCS outlining the WM network. In summary, anodal tDCS caused increased neuronal activation and connectivity, not only in the brain area under the stimulating electrode (i.e. left DLPFC) but also in other, more remote brain regions. Because of moderate behavioral effects of tDCS, the significance of this technique for ADHD treatment has to be investigated in further studies.

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

PubMed

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.

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

PubMed

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 < 0.05). tDCS also decreased total and preferred food intake by 11 and 17.5%, regardless of sex (p < 0.05), and reduced desire to binge eat in men on the day of real tDCS administration (p < 0.05). The reductions in craving and food intake were predicted by eating less frequently for reward motives, and greater intent to restrict calories, respectively. This proof of concept study is the first to find ameliorating effects of 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.

Evaluation of DCS III Transmission Alternatives. Phase 1A report. Appendix B. Regulatory Barriers.

DTIC Science & Technology

1980-05-26

greatest impact on transmission system design, and the Q- and V-series deal with switching and signaling, and with data transmission respectively. These...equipments or systems (such as receiver performance papameters). If appropriate technical data are not found in the NTIA Manual provisions of the ITU Radio...under control of the JCS and complying with applicable restrictions. 3. System alternatives should be consistent with projected data prepared for the

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

PubMed

Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

2017-11-01

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Immune phenotype in children with therapy-naïve remitted and relapsed Crohn’s disease

PubMed Central

Cseh, Aron; Vasarhelyi, Barna; Molnar, Kriszta; Szalay, Balazs; Svec, Peter; Treszl, Andras; Dezsofi, Antal; Lakatos, Peter Laszlo; Arato, Andras; Tulassay, Tivadar; Veres, Gabor

2010-01-01

AIM: To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy-naïve childhood Crohn’s disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease. METHODS: We enrolled 26 pediatric patients with CD. 14 therapy-naïve CD children; of those, 10 children remitted on conventional therapy and formed the remission group. We also tested another group of 12 children who relapsed with conventional therapy and were given infliximab; and 15 healthy children who served as controls. The prevalence of Th1 and Th2, naïve and memory, activated and regulatory T cells, along with the members of innate immunity such as natural killer (NK), NK-T, myeloid and plasmocytoid dendritic cells (DCs), monocytes and Toll-like receptor (TLR)-2 and TLR-4 expression were determined in peripheral blood samples. RESULTS: Children with therapy-naïve CD and those in relapse showed a decrease in Th1 cell prevalence. Simultaneously, an increased prevalence of memory and activated lymphocytes along with that of DCs and monocytes was observed. In addition, the ratio of myeloid /plasmocytoid DCs and the prevalence of TLR-2 or TLR-4 positive DCs and monocytes were also higher in therapy-naïve CD than in controls. The majority of alterations diminished in remitted CD irrespective of whether remission was obtained by conventional or biological therapy. CONCLUSION: The finding that immune phenotype is normalized in remission suggests a link between immune phenotype and disease activity in childhood CD. Our observations support the involvement of members of the adaptive and innate immune systems in childhood CD. PMID:21157977

The probability and severity of decompression sickness

PubMed Central

Hada, Ethan A.; Vann, Richard D.; Denoble, Petar J.

2017-01-01

Decompression sickness (DCS), which is caused by inert gas bubbles in tissues, is an injury of concern for scuba divers, compressed air workers, astronauts, and aviators. Case reports for 3322 air and N2-O2 dives, resulting in 190 DCS events, were retrospectively analyzed and the outcomes were scored as (1) serious neurological, (2) cardiopulmonary, (3) mild neurological, (4) pain, (5) lymphatic or skin, and (6) constitutional or nonspecific manifestations. Following standard U.S. Navy medical definitions, the data were grouped into mild—Type I (manifestations 4–6)–and serious–Type II (manifestations 1–3). Additionally, we considered an alternative grouping of mild–Type A (manifestations 3–6)–and serious–Type B (manifestations 1 and 2). The current U.S. Navy guidance allows for a 2% probability of mild DCS and a 0.1% probability of serious DCS. We developed a hierarchical trinomial (3-state) probabilistic DCS model that simultaneously predicts the probability of mild and serious DCS given a dive exposure. Both the Type I/II and Type A/B discriminations of mild and serious DCS resulted in a highly significant (p << 0.01) improvement in trinomial model fit over the binomial (2-state) model. With the Type I/II definition, we found that the predicted probability of ‘mild’ DCS resulted in a longer allowable bottom time for the same 2% limit. However, for the 0.1% serious DCS limit, we found a vastly decreased allowable bottom dive time for all dive depths. If the Type A/B scoring was assigned to outcome severity, the no decompression limits (NDL) for air dives were still controlled by the acceptable serious DCS risk limit rather than the acceptable mild DCS risk limit. However, in this case, longer NDL limits were allowed than with the Type I/II scoring. The trinomial model mild and serious probabilities agree reasonably well with the current air NDL only with the Type A/B scoring and when 0.2% risk of serious DCS is allowed. PMID:28296928

BDNF Val66Met but not transcranial direct current stimulation affects motor learning after stroke.

PubMed

van der Vliet, Rick; Ribbers, Gerard M; Vandermeeren, Yves; Frens, Maarten A; Selles, Ruud W

tDCS is a non-invasive neuromodulation technique that has been reported to improve motor skill learning after stroke. However, the contribution of tDCS to motor skill learning has only been investigated in a small number of studies. In addition, it is unclear if tDCS effects are mediated by activity-dependent BDNF release and dependent on timing of tDCS relative to training. Investigate the role of activity-dependent BDNF release and timing of tDCS relative to training in motor skill learning. Double-blind, between-subjects randomized controlled trial of circuit tracing task improvement (ΔMotor skill) in 80 chronic stroke patients who underwent tDCS and were genotyped for BDNF Val66Met. Patients received either short-lasting tDCS (20 min) during training (short-lasting online group), long-lasting tDCS (10 min-25 min break - 10 min) one day before training (long-lasting offline group), short-lasting tDCS one day before training (short-lasting offline group), or sham tDCS. ΔMotor skill was defined as the skill difference on the circuit tracing task between day one and day nine of the study. Having at least one BDNF Met allele was found to diminish ΔMotor skill (β BDNF,Met  = -0.217 95%HDI = [-0.431 -0.0116]), indicating activity-dependent BDNF release is important for motor skill learning after stroke. However, none of the tDCS protocols affected ΔMotor skill (β Short-lasting,online  = 0.0908 95%HDI = [-0.227 0.403]; β Long-lasting,offline  = 0.0242 95%HDI = [-0.292 0.349]; β Short-lasting,offline  = -0.108 95%HDI = [-0.433 0.210]). BDNF Val66Met is a determinant of motor skill learning after stroke and could be important for prognostic models. tDCS does not modulate motor skill learning in our study and might be less effective than previously assumed. Copyright © 2017 Elsevier Inc. All rights reserved.

Digital control for the condensate system in a combined cycle power plant

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

Sanchez Parra, M.; Fuentes Gutierrez, J.E.; Castelo Cuevas, L.

1994-12-31

This paper presents the highlights by means of which development, installation and start up of the digital control system (DCS)for the condenser and hotwell (condensate system) were performed. This system belongs to the distributed control system installed by the Instituto de Investigaciones Electricas (IIE) at the Combined Cycle Power Plant in Gomez Palacio (GP), Durango, Mexico, during the February-March period, in 1993. The main steps for development of the condenser and hotwell control system include: process modeling, definition of control strategies, algorithms, design and software development, PC simulation tests, laboratory tests with an equipment similar to the one installed atmore » the GP Power Plant, installation, and finally, start up, which was a joint effort with the GP Power Plant engineering staff.« less

Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production.

PubMed

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

2011-12-01

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 DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A-tDCS by employing the semantic interference (SI-)Effect - a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language-related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro-rehabilitation of frontal language functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deciphering the message broadcast by tumor-infiltrating dendritic cells.

PubMed

Karthaus, Nina; Torensma, Ruurd; Tel, Jurjen

2012-09-01

Human dendritic cells (DCs) infiltrate solid tumors, but this infiltration occurs in favorable and unfavorable disease prognoses. The statistical inference is that tumor-infiltrating DCs (TIDCs) play no conclusive role in predicting disease progression. This is remarkable because DCs are highly specialized antigen-presenting cells linking innate and adaptive immunity. DCs either boost the immune system (enhancing immunity) or dampen it (leading to tolerance). This dual effect explains the dual outcomes of cancer progression. The reverse functional characteristics of DCs depend on their maturation status. This review elaborates on the markers used to detect DCs in tumors. In many cases, the identification of DCs in human cancers relies on staining for S-100 and CD1a. These two markers are mainly expressed by Langerhans cells, which are one of several functionally different DC subsets. The activation status of DCs is based on the expression of CD83, DC-SIGN, and DC-LAMP, which are nonspecific markers of DC maturation. The detection of TIDCs has not kept pace with the increased knowledge about the identification of DC subsets and their maturation status. Therefore, it is difficult to draw a conclusion about the performance of DCs in tumors. We suggest a novel selection of markers to distinguish human DC subsets and maturation states. The use of these biomarkers will be of pivotal importance to scrutinize the prognostic significance of TIDCs. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Theoretical calculation on ICI reduction using digital coherent superposition of optical OFDM subcarrier pairs in the presence of laser phase noise.

PubMed

Yi, Xingwen; Xu, Bo; Zhang, Jing; Lin, Yun; Qiu, Kun

2014-12-15

Digital coherent superposition (DCS) of optical OFDM subcarrier pairs with Hermitian symmetry can reduce the inter-carrier-interference (ICI) noise resulted from phase noise. In this paper, we show two different implementations of DCS-OFDM that have the same performance in the presence of laser phase noise. We complete the theoretical calculation on ICI reduction by using the model of pure Wiener phase noise. By Taylor expansion of the ICI, we show that the ICI power is cancelled to the second order by DCS. The fourth order term is further derived out and only decided by the ratio of laser linewidth to OFDM subcarrier symbol rate, which can greatly simplify the system design. Finally, we verify our theoretical calculations in simulations and use the analytical results to predict the system performance. DCS-OFDM is expected to be beneficial to certain optical fiber transmissions.

Long-term administration of pDC-Stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice.

PubMed

Sugimura, Tetsu; Jounai, Kenta; Ohshio, Konomi; Suzuki, Hiroaki; Kirisako, Takayoshi; Sugihara, Yoshihiko; Fujiwara, Daisuke

2018-05-01

The decline in immune function caused by aging increases the risk of infectious diseases, tumorigeneses and chronic inflammation, resulting in accelerating senescence. We previously reported a lactic acid bacteria, Lactococcus lactis strain Plasma (synonym of Lactococcus lactis subsp. lactis JCM 5805, Lc-Plasma), that stimulates plasmacytoid dendritic cells (pDCs), which play a crucial role in phylaxis from viral infection. In this study, we investigated the anti-aging effects of long-term oral administration of Lc-Plasma in a senescence-accelerated mouse strain, SAMP6. Mice given Lc-Plasma showed a significant improvement in survival rate at 82 weeks and a decreased senescence score as compared with control mice throughout this study. Anatomic analysis at 82 weeks revealed that the frequency of altered hepatocellular foci was significantly lower, and the incidence of other pathological findings in the liver and lungs tended to be lower in Lc-Plasma mice than in control mice. Transcription level of the IL-1β gene in lungs also tended to be lower in Lc-Plasma mice. Furthermore, the thinning of skin and age-related decrease in muscle mass were also significantly suppressed in the Lc-Plasma group as compared with the control group. Consistent with these phenotypic features, pDCs activity was significantly higher in Lc-Plasma mice than in control mice. In conclusion, long-term administration of Lc-Plasma can decelerate senescence and prolong lifespan via maintenance of the immune system due to activation of pDCs. Copyright © 2018 Elsevier B.V. All rights reserved.

Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance

PubMed Central

Steinman, Ralph Marvin; Nussenzweig, Michel C.

2002-01-01

The immune system generally avoids horror autotoxicus or autoimmunity, an attack against the body's own constituents. This avoidance requires that self-reactive T cells be actively silenced or tolerized. We propose that dendritic cells (DCs) play a critical role in establishing tolerance, especially in the periphery, after functioning T cells have been produced in the thymus. In the steady state, meaning in the absence of acute infection and inflammation, DCs are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. Nevertheless, immature DCs continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature DCs silence T cells either by deleting them or by expanding regulatory T cells. This capacity of DCs to induce peripheral tolerance can work in two opposing ways in the context of infection. In acute infection, a beneficial effect should occur. The immune system would overcome the risk of developing autoimmunity and chronic inflammation if, before infection, tolerance were induced to innocuous environmental proteins as well as self antigens captured from dying infected cells. For chronic or persistent pathogens, a second but dire potential could take place. Continuous presentation of a pathogen by immature DCs, HIV-1 for example, may lead to tolerance and active evasion of protective immunity. The function of DCs in defining immunologic self provides a new focus for the study of autoimmunity and chronic immune-based diseases. PMID:11773639

Non-invasive Prefrontal/Frontal Brain Stimulation Is Not Effective in Modulating Food Reappraisal Abilities or Calorie Consumption in Obese Females

PubMed Central

Grundeis, Felicitas; Brand, Cristin; Kumar, Saurabh; Rullmann, Michael; Mehnert, Jan; Pleger, Burkhard

2017-01-01

Background/Objectives: Previous studies suggest that non-invasive transcranial direct current stimulation (tDCS) applied to the prefrontal cortex modulates food choices and calorie intake in obese humans. Participants/Methods: In the present fully randomized, placebo-controlled, within-subject and double-blinded study, we applied single sessions of anodal, cathodal, and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) and contralateral frontal operculum in 25 hungry obese women and investigated possible influences on food reappraisal abilities as well as calorie intake. We hypothesized that tDCS, (i) improves the ability to regulate the desire for visually presented foods and, (ii) reduces their consumption. Results: We could not confirm an effect of anodal or cathodal tDCS, neither on the ability to modulate the desire for visually presented foods, nor on calorie consumption. Conclusions: The present findings do not support the notion of prefrontal/frontal tDCS as a promising treatment option for obesity. PMID:28676735

Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4(+) T-cells in respiratory allergies.

PubMed

Karaki, S; Garcia, G; Tcherakian, C; Capel, F; Tran, T; Pallardy, M; Humbert, M; Emilie, D; Godot, V

2014-05-01

Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4(+) T-cells (IL-10-Tregs ) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs . We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs . We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-Tregs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs . This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs . We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Brucella discriminates between mouse dendritic cell subsets upon in vitro infection.

PubMed

Papadopoulos, Alexia; Gagnaire, Aurélie; Degos, Clara; de Chastellier, Chantal; Gorvel, Jean-Pierre

2016-01-01

Brucella is a Gram-negative bacterium responsible for brucellosis, a worldwide re-emerging zoonosis. Brucella has been shown to infect and replicate within Granulocyte macrophage colony-stimulating factor (GMCSF) in vitro grown bone marrow-derived dendritic cells (BMDC). In this cell model, Brucella can efficiently control BMDC maturation. However, it has been shown that Brucella infection in vivo induces spleen dendritic cells (DC) migration and maturation. As DCs form a complex network composed by several subpopulations, differences observed may be due to different interactions between Brucella and DC subsets. Here, we compare Brucella interaction with several in vitro BMDC models. The present study shows that Brucella is capable of replicating in all the BMDC models tested with a high infection rate at early time points in GMCSF-IL15 DCs and Flt3l DCs. GMCSF-IL15 DCs and Flt3l DCs are more activated than the other studied DC models and consequently intracellular bacteria are not efficiently targeted to the ER replicative niche. Interestingly, GMCSF-DC and GMCSF-Flt3l DC response to infection is comparable. However, the key difference between these 2 models concerns IL10 secretion by GMCSF DCs observed at 48 h post-infection. IL10 secretion can explain the weak secretion of IL12p70 and TNFα in the GMCSF-DC model and the low level of maturation observed when compared to GMCSF-IL15 DCs and Flt3l DCs. These models provide good tools to understand how Brucella induce DC maturation in vivo and may lead to new therapeutic design using DCs as cellular vaccines capable of enhancing immune response against pathogens.

Critical role for TNF in the induction of human antigen-specific regulatory T cells by tolerogenic dendritic cells.

PubMed

Kleijwegt, Fleur S; Laban, Sandra; Duinkerken, Gaby; Joosten, Antoinette M; Zaldumbide, Arnaud; Nikolic, Tatjana; Roep, Bart O

2010-08-01

TNF is a pleiotropic cytokine with differential effects on immune cells and diseases. Anti-TNF therapy was shown to be effective in rheumatoid arthritis but proved inefficient or even detrimental in other autoimmune diseases. We studied the role of TNF in the induction of Ag-specific regulatory T cells (Tregs) by tolerogenic vitamin D3-modulated human dendritic cells (VD3-DCs), which previously were shown to release high amounts of soluble TNF (sTNF) upon maturation with LPS. First, production of TNF by modulated VD3-DCs was analyzed upon maturation with LPS or CD40L with respect to both secreted (cleaved) TNF (sTNF) and expression of the membrane-bound (uncleaved) form of TNF (mTNF). Next, TNF antagonists were tested for their effect on induction of Ag-specific Tregs by modulated DCs and the subsequent functionality of these Tregs. VD3-DCs expressed greater amounts of mTNF than did control DCs (nontreated DCs), independent of the maturation protocol. Inhibition of TNF with anti-TNF Ab (blocking both sTNF and mTNF) during the priming of Tregs with VD3-DCs prevented generation of Tregs and their suppression of proliferation of CD4(+) T cells. In contrast, sTNF receptor II (sTNFRII), mainly blocking sTNF, did not change the suppressive capacity of Tregs. Blocking of TNFRII by anti-CD120b Ab during Treg induction similarly abrogated their subsequent suppressive function. These data point to a specific role for mTNF on VD3-DCs in the induction of Ag-specific Tregs. Interaction between mTNF and TNFRII instructs the induction of suppressive Tregs by VD3-DCs. Anti-TNF therapy may therefore act adversely in different patients or disease pathways.

Guidewire exchange vs new site placement for temporary dialysis catheter insertion in ICU patients: is there a greater risk of colonization or dysfunction?

PubMed

Coupez, Elisabeth; Timsit, Jean-François; Ruckly, Stéphane; Schwebel, Carole; Gruson, Didier; Canet, Emmanuel; Klouche, Kada; Argaud, Laurent; Bohe, Julien; Garrouste-Orgeas, Maïté; Mariat, Christophe; Vincent, François; Cayot, Sophie; Cointault, Olivier; Lepape, Alain; Darmon, Michael; Boyer, Alexandre; Azoulay, Elie; Bouadma, Lila; Lautrette, Alexandre; Souweine, Bertrand

2016-07-30

Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction. GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction. This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

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

PubMed

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.

Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.

PubMed

Kamboj, Sunjeev K; Massey-Chase, Rachel; Rodney, Lydia; Das, Ravi; Almahdi, Basil; Curran, H Valerie; Morgan, Celia J A

2011-09-01

The effects of D-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl D-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect. The objective of this study is to investigate the effect of DCS on exposure/response prevention in heavy drinkers. In a randomised, double-blind, placebo-controlled study, heavy social drinkers recruited from the community received either DCS (125 mg; n = 19) or placebo (n = 17) 1 h prior to each of two sessions of exposure/response prevention. Cue reactivity and attentional bias were assessed during these two sessions and at a third follow-up session. Between-session drinking behaviour was recorded. Robust cue reactivity and attentional bias to alcohol cues was evident, as expected of heavy drinkers. Within- and between-session habituation of cue reactivity, as well as a reduction in attentional bias to alcohol cues over time was found. However, there was no evidence of greater habituation in the DCS group. Subtle stimulant effects (increased subjective contentedness and euphoria) which were unrelated to exposure/response prevention were found following DCS. DCS does not appear to enhance habituation of alcohol cue reactivity in heavy non-dependent drinkers. Its utility in enhancing treatments based on exposure/response prevention in dependent drinkers or drug users remains open.

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

PubMed

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.

Effect of D-cycloserine in conjunction with fear extinction training on extracellular signal-regulated kinase activation in medial prefrontal cortex and amygdala in rat

PubMed Central

Gupta, Subhash C.; Hillman, Brandon G.; Prakash, Anand; Ugale, Rajesh R; Stairs, Dustin J.; Dravid, Shashank M.

2013-01-01

D-cycloserine (DCS) is currently under clinical trials for a number of neuropsychiatric conditions and has been found to augment fear extinction in rodents and exposure therapy in humans. However, the molecular mechanism of DCS action in these multiple modalities remains unclear. Here, we describe the effect of DCS administration, alone or in conjunction with extinction training, on neuronal activity (c-fos) and neuronal plasticity (phospho-extracellular signal-regulated kinase, pERK) markers using immunohistochemistry. We found that intraperitoneal administration of DCS in untrained young rats (24–28 days old) increased c-fos and pERK-stained neurons in both the prelimbic (PL) and infralimbic (IL) division of the medial prefrontal cortex (mPFC) and reduced pERK levels in the lateral nucleus (CeL) of the central amygdala (CeA). Moreover, DCS administration significantly increased GluA1, GluN1, GluN2A, and GluN2B expression in mPFC. In a separate set of animals, we found that DCS facilitated fear extinction and increased pERK levels in IL, PL, intercalated cells and CeL, compared to saline control. In synaptoneurosomal preparation, we found that extinction training increased iGluR protein expression in the mPFC, compared to context animals. No significant difference in protein expression was observed between extinction-saline and extinction-DCS groups in the mPFC. In contrast, in the amygdala DCS in conjunction with extinction training led to an increase in iGluR subunit expression, compared to extinction-saline group. Our data suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due to its ability to affect neuronal activity and signaling in the mPFC and amygdala subnuclei. PMID:23551217

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

PubMed

Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Effect of Transcranial Direct Current Stimulation on Severely Affected Arm-Hand Motor Function in Patients After an Acute Ischemic Stroke: A Pilot Randomized Control Trial.

PubMed

Rabadi, Meheroz H; Aston, Christopher E

2017-10-01

The aim of this article was to determine whether cathodal transcranial direct current stimulation (c-tDCS) to unaffected primary motor cortex (PMC) plus conventional occupational therapy (OT) improves functional motor recovery of the affected arm hand in patients after an acute ischemic stroke compared with sham transcranial direct current stimulation plus conventional OT. In this prospective, randomized, double-blinded, sham-controlled trial of 16 severe, acute ischemic stroke patients with severe arm-hand weakness were randomly assigned to either experimental (c-tDCS plus OT; n = 8) or control (sham transcranial direct current stimulation plus OT; n = 8) groups. All patients received a standard 3-hr in-patient rehabilitation therapy, plus an additional ten 30-min sessions of tDCS. During each session, 1 mA of cathodal stimulation to the unaffected PMC is performed followed by the patient's scheduled OT. The primary outcome measure was change in Action Research Arm Test (ARAT) total and subscores on discharge. Application of c-tDCS to unaffected PMC resulted in a clinically relevant 10-point improvement in the affected arm-hand function based on ARAT total score compared with a 2-point improvement in the control group. Application of 30-min of c-tDCS to the unaffected PMC showed a 10-point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistically significant, this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.

PubMed

Gorvel, Laurent; Textoris, Julien; Banchereau, Romain; Ben Amara, Amira; Tantibhedhyangkul, Wiwit; von Bargen, Kristin; Ka, Mignane B; Capo, Christian; Ghigo, Eric; Gorvel, Jean-Pierre; Mege, Jean-Louis

2014-01-01

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-β production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies.

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

PubMed

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

2016-06-21

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 cm(2)) 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 ([Formula: see text] · (σ [Formula: see text] V)  =  0) was solved for cortical electric field, which was interpreted using physiological assumptions to correlate with stimulation and modulation. Cortical field intensity was predicted to increase with increasing ring diameter at the cost of focality while uni-directionality decreased. Additional surrounding ring electrodes increased uni-directionality while lowering cortical field intensity and increasing focality; though, this effect saturated and more than 4 surround electrode would not be justified. Using a range of concentric HD-tDCS montages, we showed that cortical region of influence can be controlled while balancing other design factors such as intensity at the target and uni-directionality. Furthermore, the evaluated concentric HD-tDCS approaches can provide categorical improvements in targeting compared to conventional tDCS. Hypothesis driven clinical trials, based on specific target engagement, would benefit by this more precise method of stimulation that could avoid potentially confounding brain regions.

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

PubMed

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 in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The effect of D-cycloserine on subliminal cue exposure in spider fearful individuals.

PubMed

Gutner, Cassidy A; Weinberger, Joel; Hofmann, Stefan G

2012-01-01

Research on D-cycloserine (DCS) has demonstrated a significant effect on symptom reduction in human studies that utilized conventional exposure-based approaches. Recent studies have offered promising results for targeting fears through subliminal paradigms. In this double-blind, randomized placebo-controlled study, 45 spider fearful individuals received DCS or placebo pills prior to completing a subliminal cue exposure task to images of spiders. Participants completed self-report questionnaires and a behavioral approach task to a live caged tarantula. After repeated exposure to subliminal spider cues, participants in the DCS group reported a greater reduction in disgust than individuals in the placebo group. No difference was observed in fear ratings. These findings suggest that DCS augments the reduction in disgust in spider fearful subjects after subliminal exposure to spider cues.

Dendritic cell reprogramming by endogenously produced lactic acid.

PubMed

Nasi, Aikaterini; Fekete, Tünde; Krishnamurthy, Akilan; Snowden, Stuart; Rajnavölgyi, Eva; Catrina, Anca I; Wheelock, Craig E; Vivar, Nancy; Rethi, Bence

2013-09-15

The demand for controlling T cell responses via dendritic cell (DC) vaccines initiated a quest for reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce inflammatory or suppressor programs during differentiation, and we identified a powerful autocrine pathway that, in a cell concentration-dependent manner, strongly interferes with inflammatory DC differentiation. MoDCs developing at low cell culture density have superior ability to produce inflammatory cytokines, to induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no inflammatory cytokines upon activation. DCs from high-density cultures maintained more differentiation plasticity and can develop to osteoclasts. The cell concentration-dependent pathway was independent of peroxisome proliferator-activated receptor γ (PPARγ), a known endogenous regulator of MoDC differentiation. Instead, it acted through lactic acid, which accumulated in dense cultures and induced an early and long-lasting reprogramming of MoDC differentiation. Our results suggest that the lactic acid-mediated inhibitory pathway could be efficiently manipulated in developing MoDCs to influence the immunogenicity of DC vaccines.

Biotin deficiency enhances the inflammatory response of human dendritic cells.

PubMed

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.

Biotin deficiency enhances the inflammatory response of human dendritic cells

PubMed Central

Agrawal, Sudhanshu; Said, Hamid M.

2016-01-01

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. PMID:27413170

Occipital Nerve Field Transcranial Direct Current Stimulation Normalizes Imbalance Between Pain Detecting and Pain Inhibitory Pathways in Fibromyalgia.

PubMed

De Ridder, Dirk; Vanneste, Sven

2017-04-01

Occipital nerve field (OCF) stimulation with subcutaneously implanted electrodes is used to treat headaches, more generalized pain, and even failed back surgery syndrome via unknown mechanisms. Transcranial direct current stimulation (tDCS) can predict the efficacy of implanted electrodes. The purpose of this study is to unravel the neural mechanisms involved in global pain suppression, mediated by occipital nerve field stimulation, within the realm of fibromyalgia. Nineteen patients with fibromyalgia underwent a placebo-controlled OCF tDCS. Electroencephalograms were recorded at baseline after active and sham stimulation. In comparison with healthy controls, patients with fibromyalgia demonstrate increased dorsal anterior cingulate cortex, increased premotor/dorsolateral prefrontal cortex activity, and an imbalance between pain-detecting dorsal anterior cingulate cortex and pain-suppressing pregenual anterior cingulate cortex activity, which is normalized after active tDCS but not sham stimulation associated with increased pregenual anterior cingulate cortex activation. The imbalance improvement between the pregenual anterior cingulate cortex and the dorsal anterior cingulate cortex is related to clinical changes. An imbalance assumes these areas communicate and, indeed, abnormal functional connectivity between the dorsal anterior cingulate cortex and pregenual anterior cingulate cortex is noted to be caused by a dysfunctional effective connectivity from the pregenual anterior cingulate cortex to the dorsal anterior cingulate cortex, which improves and normalizes after real tDCS but not sham tDCS. In conclusion, OCF tDCS exerts its effect via activation of the descending pain inhibitory pathway and de-activation of the salience network, both of which are abnormal in fibromyalgia.

A rat model of chronic moderate alcohol consumption and risk of decompression sickness.

PubMed

Buzzacott, Peter; Mazur, Aleksandra; Wang, Qiong; Lambrechts, Kate; Theron, Michael; Guerrero, François

2015-06-01

This study aimed to establish if chronic, moderate, pre-dive alcohol consumption had any affect upon susceptibility to decompression sickness (DCS) in rats. A treatment group of 15 rats were given water containing 12 mL ·L ⁻¹ of ethanol for four weeks. Controls (n = 15) were given water. Both groups were compressed with air to 1,000 kPa, followed by staged decompression. An additional 30 control rats from a similar previous experiment were added, raising the control-treatment ratio to 3:1. Rats in the treatment group consumed the equivalent of an 80 kg man drinking 2 L of 5 % alcohol by volume beer per day, which is three times the recommended daily limit for men. Overall, comparing the treatment group with the combined control groups neither weight (P = 0.23) nor alcohol consumption (P = 0.69) were associated with DCS. We observed that chronic, moderate alcohol consumption prior to compression was neither prophylactic nor deleterious for DCS in young, male rats.

Enhancing social ability by stimulating right temporoparietal junction.

PubMed

Santiesteban, Idalmis; Banissy, Michael J; Catmur, Caroline; Bird, Geoffrey

2012-12-04

The temporoparietal junction (TPJ) is a key node within the "social brain". Several studies suggest that the TPJ controls representations of the self or another individual across a variety of low-level (agency discrimination, visual perspective taking, control of imitation) and high-level (mentalizing, empathy) sociocognitive processes. We explored whether sociocognitive abilities relying on on-line control of self and other representations could be modulated with transcranial direct current stimulation (tDCS) of TPJ. Participants received excitatory (anodal), inhibitory (cathodal), or sham stimulation before completing three sociocognitive tasks. Anodal stimulation improved the on-line control of self-other representations elicited by the imitation and perspective-taking tasks while not affecting attribution of mental states during a self-referential task devoid of such a requirement. Our findings demonstrate the efficacy of tDCS to improve social cognition and highlight the potential for tDCS to be used as a tool to aid self-other processing in clinical populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lactobacillus paracasei CNCM I-4034 and its culture supernatant modulate Salmonella-induced inflammation in a novel transwell co-culture of human intestinal-like dendritic and Caco-2 cells.

PubMed

Bermudez-Brito, Miriam; Muñoz-Quezada, Sergio; Gómez-Llorente, Carolina; Matencio, Esther; Romero, Fernando; Gil, Angel

2015-04-01

The action of probiotics has been studied in vitro in cells isolated from both mice and humans, particularly enterocytes (IECs), dendritic cells (DCs) and co-cultures of peripheral DCs and IECs. Peripheral DCs and murine DCs differ from human gut DCs, and to date there are no data on the action of any probiotic on co-cultured human IECs and human intestinal DCs. To address this issue, a novel transwell model was used. Human IECs (Caco-2 cells) grown in the upper chamber of transwell filters were co-cultured with intestinal-like human DCs grown in the basolateral compartment of the transwells. The system was apically exposed for 4 h to live probiotic L. paracasei CNCM I-4034 obtained from the faeces of breastfed infants or to its cell-free culture supernatant (CFS) and challenged with Salmonella typhi. The secretion of pro- and anti-inflammatory cytokines in the basolateral compartment was determined by immunoassay, and the DC expression pattern of 20 TLR signaling pathway genes was analysed by PCR array. The presence of the live probiotic alone significantly increased IL-1β, IL-6, IL-8, TGF-β2, RANTES and IP-10 levels and decreased IL-12p40, IL-10, TGF- β1 and MIP-1α levels. This release was correlated with a significant increase in the expression of almost all TLR signaling genes. By contrast, incubation of the co-culture with CFS increased IL-1β, IL-6, TGF-β2 and IP-10 production only when Salmonella was present. This induction was correlated with an overall decrease in the expression of all TLR genes except TLR9, which was strongly up-regulated. The data presented here clearly indicate that L. paracasei CNCM I-4034 significantly increases the release of pro-inflammatory cytokines, enhances TLR signaling pathway activation and stimulates rather than suppresses the innate immune system. Furthermore, our findings provide evidence that the effects of probiotics in the presence of IECs and DCs differ from the effects of probiotics on cultures of each cell type alone, as reported by us earlier. Thus, co-culture systems such as the one described here are needed to characterise the effects of probiotics in vitro, highlighting the potential utility of such co-cultures as a model system.

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

PubMed

Rueger, Maria Adele; Keuters, Meike Hedwig; Walberer, Maureen; Braun, Ramona; Klein, Rebecca; Sparing, Roland; Fink, Gereon Rudolf; Graf, Rudolf; Schroeter, Michael

2012-01-01

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.

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.

PubMed

Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

2016-09-15

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii.

PubMed

John, Beena; Harris, Tajie H; Tait, Elia D; Wilson, Emma H; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A

2009-07-01

To better understand the initiation of CD8(+) T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8(+) T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8(+) T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8(+) T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8(+) T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis.

Dynamic Imaging of CD8+ T Cells and Dendritic Cells during Infection with Toxoplasma gondii

PubMed Central

John, Beena; Harris, Tajie H.; Tait, Elia D.; Wilson, Emma H.; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S.; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A.

2009-01-01

To better understand the initiation of CD8+ T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8+ T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8+ T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8+ T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8+ T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis. PMID:19578440

Mission Control Center (MCC) System Specification for the Shuttle Orbital Flight Test (OFT) Timeframe

NASA Technical Reports Server (NTRS)

1976-01-01

System specifications to be used by the mission control center (MCC) for the shuttle orbital flight test (OFT) time frame were described. The three support systems discussed are the communication interface system (CIS), the data computation complex (DCC), and the display and control system (DCS), all of which may interfere with, and share processing facilities with other applications processing supporting current MCC programs. The MCC shall provide centralized control of the space shuttle OFT from launch through orbital flight, entry, and landing until the Orbiter comes to a stop on the runway. This control shall include the functions of vehicle management in the area of hardware configuration (verification), flight planning, communication and instrumentation configuration management, trajectory, software and consumables, payloads management, flight safety, and verification of test conditions/environment.

Transcranial direct current stimulation of the medial prefrontal cortex dampens mind-wandering in men.

PubMed

Bertossi, Elena; Peccenini, Ludovica; Solmi, Andrea; Avenanti, Alessio; Ciaramelli, Elisa

2017-12-05

Mind-wandering, the mind's capacity to stray from external events and generate task-unrelated thought, has been associated with activity in the brain default network. To date, little is understood about the contribution of individual nodes of this network to mind-wandering. Here, we investigated the role of medial prefrontal cortex (mPFC) in mind-wandering, by perturbing this region with transcranial direct current stimulation (tDCS). Young healthy participants performed a choice reaction time task both before and after receiving cathodal tDCS over mPFC, and had their thoughts periodically sampled. We found that tDCS over mPFC - but not occipital or sham tDCS - decreased the propensity to mind-wander. The tDCS-induced reduction in mind-wandering occurred in men, but not in women, and was accompanied by a change in the content of task-unrelated though, which became more related to other people (as opposed to the self) following tDCS. These findings indicate that mPFC is crucial for mind-wandering, possibly by helping construction of self-relevant scenarios capable to divert attention inward, away from perceptual reality. Gender-related differences in tDCS-induced changes suggest that mPFC controls mind-wandering differently in men and women, which may depend on differences in the structural and functional organization of distributed brain networks governing mind-wandering, including mPFC.

NKG2D is Required for Regulation of Lung Pathology and Dendritic Cell Function Following RSV Infection.

PubMed

Liu, Huan; Osterburg, Andrew R; Flury, Jennifer; Huang, Shuo; McCormack, Francis X; Cormier, Stephania A; Borchers, Michael T

2018-03-15

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infection in vulnerable populations. Natural killer (NK) cells and dendritic cells (DC) are important for the effector functions of both cell types following infection. Wild type and NKG2D deficient mice were infected with RSV. Lung pathology, was assessed by histology. DC function and phenotype was evaluated by ELISA and flow cytometry. The expression of NKG2D ligands on lung and lymph node DCs was measured by immunostaining and flow cytometry. Adoptive transfer experiments were performed to assess the importance of NKG2D dependent DC function in RSV infection. NKG2D deficient mice exhibited greater lung pathology, marked by the accumulation of DCs following RSV infection.  DCs isolated from NKG2D deficient mice had impaired responses towards TLR ligands. DCs expressed NKG2D ligands on their surface, which was further increased in NKG2D deficient mice and during RSV infection. Adoptive transfer of DCs isolated from WT mice into the airways of NKG2D deficient mice ameliorated the enhanced inflammation in NKG2D deficient mice after RSV infection. NKG2D-dependent interactions with DCs control the phenotype and function of DCs and play a critical role in pulmonary host defenses against RSV infection.

Formation of cortical plasticity in older adults following tDCS and motor training

PubMed Central

Goodwill, Alicia M.; Reynolds, John; Daly, Robin M.; Kidgell, Dawson J.

2013-01-01

Neurodegeneration accompanies the process of natural aging, reducing the ability to perform functional daily activities. Transcranial direct current stimulation (tDCS) alters neuronal excitability and motor performance; however its beneficial effect on the induction of primary motor cortex (M1) plasticity in older adults is unclear. Moreover, little is known as to whether the tDCS electrode arrangement differentially affects M1 plasticity and motor performance in this population. In a double-blinded, cross-over trial, we compared unilateral, bilateral and sham tDCS combined with visuomotor tracking, on M1 plasticity and motor performance of the non-dominant upper limb, immediately post and 30 min following stimulation. We found (a) unilateral and bilateral tDCS decreased tracking error by 12–22% at both time points; with sham decreasing tracking error by 10% at 30 min only, (b) at both time points, motor evoked potentials (MEPs) were facilitated (38–54%) and short-interval intracortical inhibition was released (21–36%) for unilateral and bilateral conditions relative to sham, (c) there were no differences between unilateral and bilateral conditions for any measure. These findings suggest that tDCS modulated elements of M1 plasticity, which improved motor performance irrespective of the electrode arrangement. The results provide preliminary evidence indicating that tDCS is a safe non-invasive tool to preserve or improve neurological function and motor control in older adults. PMID:24367333

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis.

PubMed

Tedesco Triccas, L; Burridge, J H; Hughes, A M; Pickering, R M; Desikan, M; Rothwell, J C; Verheyden, G

2016-01-01

To systematically review the methodology in particular treatment options and outcomes and the effect of multiple sessions of transcranial direct current stimulation (tDCS) with rehabilitation programmes for upper extremity recovery post stroke. A search was conducted for randomised controlled trials involving tDCS and rehabilitation for the upper extremity in stroke. Quality of included studies was analysed using the Modified Downs and Black form. The extent of, and effect of variation in treatment parameters such as anodal, cathodal and bi-hemispheric tDCS on upper extremity outcome measures of impairment and activity were analysed using meta-analysis. Nine studies (371 participants with acute, sub-acute and chronic stroke) were included. Different methodologies of tDCS and upper extremity intervention, outcome measures and timing of assessments were identified. Real tDCS combined with rehabilitation had a small non-significant effect of +0.11 (p=0.44) and +0.24 (p=0.11) on upper extremity impairments and activities at post-intervention respectively. Various tDCS methods have been used in stroke rehabilitation. The evidence so far is not statistically significant, but is suggestive of, at best, a small beneficial effect on upper extremity impairment. Future research should focus on which patients and rehabilitation programmes are likely to respond to different tDCS regimes. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of transcranial direct current stimulation (tDCS) on MMN-indexed auditory discrimination: a pilot study.

PubMed

Impey, Danielle; Knott, Verner

2015-08-01

Membrane potentials and brain plasticity are basic modes of cerebral information processing. Both can be externally (non-invasively) modulated by weak transcranial direct current stimulation (tDCS). Polarity-dependent tDCS-induced reversible circumscribed increases and decreases in cortical excitability and functional changes have been observed following stimulation of motor and visual cortices but relatively little research has been conducted with respect to the auditory cortex. The aim of this pilot study was to examine the effects of tDCS on auditory sensory discrimination in healthy participants (N = 12) assessed with the mismatch negativity (MMN) brain event-related potential (ERP). In a randomized, double-blind, sham-controlled design, participants received anodal tDCS over the primary auditory cortex (2 mA for 20 min) in one session and 'sham' stimulation (i.e., no stimulation except initial ramp-up for 30 s) in the other session. MMN elicited by changes in auditory pitch was found to be enhanced after receiving anodal tDCS compared to 'sham' stimulation, with the effects being evidenced in individuals with relatively reduced (vs. increased) baseline amplitudes and with relatively small (vs. large) pitch deviants. Additional studies are needed to further explore relationships between tDCS-related parameters, auditory stimulus features and individual differences prior to assessing the utility of this tool for treating auditory processing deficits in psychiatric and/or neurological disorders.

HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation

NASA Astrophysics Data System (ADS)

Granelli-Piperno, Angela; Golebiowska, Angelika; Trumpfheller, Christine; Siegal, Frederick P.; Steinman, Ralph M.

2004-05-01

Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced.

Harnessing dendritic cells in inflammatory skin diseases

PubMed Central

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O.

2011-01-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. PMID:21295490

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

PubMed Central

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

2016-01-01

Objective Current chronic pain treatments target nociception rather than affective “suffering” and its associated functional and psychiatric comorbidities. 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 noninvasively modulate cortical activity. The present study tests if anodal tDCS targeting left DLPFC will increase tolerability of acute painful stimuli versus cathodal tDCS. Methods Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting 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. Results Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (all p > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal versus cathodal tDCS (p = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (p = 0.042) on CP threshold suggesting task sensitization. Conclusions Although our results do not suggest that polarity of tDCS targeting left DLPFC differentially modulates 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 left dorsal anterior cingulate cortex showed a trend towards higher mean CP tolerance with cathodal versus 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 DVPRS. Sham-controlled clinical studies are needed. PMID:26814276

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

PubMed

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 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transcranial direct current stimulation associated with gait training in Parkinson's disease: A pilot randomized clinical trial.

PubMed

Costa-Ribeiro, Adriana; Maux, Ariadne; Bosford, Thamyris; Aoki, Yumi; Castro, Rebeca; Baltar, Adriana; Shirahige, Lívia; Moura Filho, Alberto; Nitsche, Michael A; Monte-Silva, Kátia

2017-04-01

The aim of this study is to investigate the effects of transcranial direct current stimulation (tDCS) combined with cueing gait training (CGT) on functional mobility in patients with Parkinson´s disease (PD). A pilot double-blind controlled, randomized clinical trial was conducted with 22 patients with PD assigned to the experimental (anodal tDCS plus CGT) and control group (sham tDCS plus CGT). The primary outcome (functional mobility) was assessed by 10-m walk test, cadence, stride length, and Timed Up and Go test. Motor impairment, bradykinesia, balance, and quality of life were analyzed as secondary outcomes. Minimal clinically important differences (MCIDs) were observed when assessing outcome data. Both groups demonstrated similar gains in all outcome measures, except for the stride length. The number of participants who showed MCID was similar between groups. The CGT provided many benefits to functional mobility, motor impairment, bradykinesia, balance, and quality of life. However, these effect magnitudes were not influenced by stimulation, but tDCS seems to prolong the effects of cueing therapy on functional mobility.

Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion

NASA Astrophysics Data System (ADS)

Schmieg, John; Yang, Guangli; Franck, Richard W.; van Rooijen, Nico; Tsuji, Moriya

2005-01-01

It has been shown that dendritic cells (DCs) are able to present glycolipids to natural killer (NK) T cells in vivo. However, the essential role of DCs, as well as the role of other cells in glycolipid presentation, is unknown. Here, we show that DCs are the crucial antigen-presenting cells (APCs) for splenic NK T cells, whereas Kupffer cells are the key APCs for hepatic NK T cells. Both cell types stimulate cytokine production by NK T cells within 2 h of glycolipid administration, but only DCs are involved in the systemic, downstream responses to glycolipid administration. More specifically, CD8+ DCs produce IL-12 in response to glycolipid presentation, which stimulates secondary IFN- production by NK cells in different organs. Different APCs participate in glycolipid presentation to NK T cells in vivo but differ in their involvement in the overall glycolipid response. dendritic cell | Kupffer cell

A Feasibility Study on the Application of the ScriptGenE Framework as an Anomaly Detection System in Industrial Control Systems

DTIC Science & Technology

2015-09-17

network intrusion detection systems NIST National Institute of Standards and Technology p-tree protocol tree PI protocol informatics PLC programmable logic...electrical, water, oil , natural gas, manufacturing, and pharmaceutical industries, to name a few. The differences between SCADA and DCS systems are often... Oil Company, also known as Saudi Aramco, suffered huge data loss that resulted in the disruption of daily operations for nearly two weeks [BTR13]. As it

A generalized baleen whale call detection and classification system.

PubMed

Baumgartner, Mark F; Mussoline, Sarah E

2011-05-01

Passive acoustic monitoring allows the assessment of marine mammal occurrence and distribution at greater temporal and spatial scales than is now possible with traditional visual surveys. However, the large volume of acoustic data and the lengthy and laborious task of manually analyzing these data have hindered broad application of this technique. To overcome these limitations, a generalized automated detection and classification system (DCS) was developed to efficiently and accurately identify low-frequency baleen whale calls. The DCS (1) accounts for persistent narrowband and transient broadband noise, (2) characterizes temporal variation of dominant call frequencies via pitch-tracking, and (3) classifies calls based on attributes of the resulting pitch tracks using quadratic discriminant function analysis (QDFA). Automated detections of sei whale (Balaenoptera borealis) downsweep calls and North Atlantic right whale (Eubalaena glacialis) upcalls were evaluated using recordings collected in the southwestern Gulf of Maine during the spring seasons of 2006 and 2007. The accuracy of the DCS was similar to that of a human analyst: variability in differences between the DCS and an analyst was similar to that between independent analysts, and temporal variability in call rates was similar among the DCS and several analysts.

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

PubMed

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.

Improvement of Upper Extremity Deficit after Constraint-Induced Movement Therapy Combined with and without Preconditioning Stimulation Using Dual-hemisphere Transcranial Direct Current Stimulation and Peripheral Neuromuscular Stimulation in Chronic Stroke Patients: A Pilot Randomized Controlled Trial.

PubMed

Takebayashi, Takashi; Takahashi, Kayoko; Moriwaki, Misa; Sakamoto, Tomosaburo; Domen, Kazuhisa

2017-01-01

In this study, we investigated the effects of dual-hemisphere transcranial direct current stimulation (dual-tDCS) of both the affected (anodal tDCS) and non-affected (cathodal tDCS) primary motor cortex, combined with peripheral neuromuscular electrical stimulation (PNMES), on the effectiveness of constraint-induced movement therapy (CIMT) as a neurorehabilitation intervention in chronic stroke. We conducted a randomized controlled trial of feasibility, with a single blind assessor, with patients recruited from three outpatient clinics. Twenty chronic stroke patients were randomly allocated to the control group, receiving conventional CIMT, or the intervention group receiving dual-tDCS combined with PNMES before CIMT. Patients in the treatment group first underwent a 20-min period of dual-tDCS, followed immediately by PNMES, and subsequent CIMT for 2 h. Patients in the control group only received CIMT (with no pretreatment stimulation). All patients underwent two CIMT sessions, one in the morning and one in the afternoon, each lasting 2 h, for a total of 4 h of CIMT per day. Upper extremity function was assessed using the Fugl-Meyer Assessment (primary outcome), as well as the amount of use (AOU) and quality of movement (QOM) scores, obtained via the Motor Activity Log (secondary outcome). Nineteen patients completed the study, with one patient withdrawing after allocation. Compared to the control group, the treatment improvement in upper extremity function and AOU was significantly greater in the treatment than control group (change in upper extremity score, 9.20 ± 4.64 versus 4.56 ± 2.60, respectively, P  < 0.01, η 2  = 0.43; change in AOU score, 1.10 ± 0.65 versus 0.62 ± 0.85, respectively, P  = 0.02, η 2  = 0.52). There was no significant effect of the intervention on the QOM between the intervention and control groups (change in QOM score, 1.00 ± 0.62 versus 0.71 ± 0.72, respectively, P  = 0.07, η 2  = 0.43; treatment versus control). Our findings suggest a novel pretreatment stimulation strategy based on dual-tDCS and PNMES may enhance the therapeutic benefit of CIMT.

D.C.'s Braveheart

ERIC Educational Resources Information Center

Kronholz, June

2010-01-01

This article discusses Michelle Rhee's style of leadership--as steely as the sound of her peekaboo high heels on a linoleum-tile hallway--which has angered much of Washington, D.C., and baffled the rest since she arrived as schools chancellor in June 2007. But it is also helping her gain control of a school system that has defied management for…

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

PubMed

Santa Ana, Elizabeth J; Prisciandaro, James J; Saladin, Michael E; McRae-Clark, Aimee L; Shaftman, Stephanie R; Nietert, Paul J; Brady, Kathleen T

2015-04-01

Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity. © American Academy of Addiction Psychiatry.

Effects of transcranial direct current stimulation over the supplementary motor area body weight-supported treadmill gait training in hemiparetic patients after stroke.

PubMed

Manji, Atsushi; Amimoto, Kazu; Matsuda, Tadamitsu; Wada, Yoshiaki; Inaba, Akira; Ko, Sangkyun

2018-01-01

Transcranial direct current stimulation (tDCS) is used in a variety of disorders after stroke including upper limb motor dysfunctions, hemispatial neglect, aphasia, and apraxia, and its effectiveness has been demonstrated. Although gait ability is important for daily living, there were few reports of the use of tDCS to improve balance and gait ability. The supplementary motor area (SMA) was reported to play a potentially important role in balance recovery after stroke. We aimed to investigate the effect of combined therapy body weight-supported treadmill training (BWSTT) and tDCS on gait function recovery of stroke patients. Thirty stroke inpatients participated in this study. The two BWSTT periods of 1weeks each, with real tDCS (anode: front of Cz, cathode: inion, 1mA, 20min) on SMA and sham stimulation, were randomized in a double-blind crossover design. We measured the time required for the 10m Walk Test (10MWT) and Timed Up and Go (TUG) test before and after each period. We found that the real tDCS with BWSTT significantly improved gait speed (10MWT) and applicative walking ability (TUG), compared with BWSTT+sham stimulation periods (p<0.05). Our findings demonstrated the feasibility and efficacy of tDCS in gait training after stroke. The facilitative effects of tDCS on SMA possibly improved postural control during BWSTT. The results indicated the implications for the use of tDCS in balance and gait training rehabilitation after stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasmacytoid Dendritic Cells in the Tumor Microenvironment: Immune Targets for Glioma Therapeutics12

PubMed Central

Candolfi, Marianela; King, Gwendalyn D; Yagiz, Kader; Curtin, James F; Mineharu, Yohei; Muhammad, AKM Ghulam; Foulad, David; Kroeger, Kurt M; Barnett, Nick; Josien, Regis; Lowenstein, Pedro R; Castro, Maria G

2012-01-01

Adenovirus-mediated delivery of the immune-stimulatory cytokine Flt3L and the conditionally cytotoxic thymidine kinase (TK) induces tumor regression and long-term survival in preclinical glioma (glioblastoma multiforme [GBM]) models. Flt3L induces expansion and recruitment of plasmacytoid dendritic cells (pDCs) into the brain. Although pDCs can present antigen and produce powerful inflammatory cytokines, that is, interferon α (IFN-α), their role in tumor immunology remains debated. Thus, we studied the role of pDCs and IFN-α in Ad.TK/GCV+ Ad.Flt3L-mediated anti-GBM therapeutic efficacy. Our data indicate that the combined gene therapy induced recruitment of plasmacytoid DCs (pDCs) into the tumor mass; which were capable of in vivo phagocytosis, IFN-α release, and T-cell priming. Thus, we next used either pDCs or an Ad vector encoding IFN-α delivered within the tumor microenvironment. When rats were treated with Ad.TK/GCV in combination with pDCs or Ad-IFN-α, they exhibited 35% and 50% survival, respectively. However, whereas intracranial administration of Ad.TK/GCV + Ad.Flt3L exhibited a high safety profile, Ad-IFN-α led to severe local inflammation, with neurologic and systemic adverse effects. To elucidate whether the efficacy of the immunotherapy was dependent on IFN-α-secreting pDCs, we administered an Ad vector encoding B18R, an IFN-α antagonist, which abrogated the antitumoral effect of Ad.TK/GCV + Ad.Flt3L. Our data suggest that IFN-α release by activated pDCs plays a critical role in the antitumor effect mediated by Ad.TK/GCV + Ad.Flt3L. In summary, taken together, our results demonstrate that pDCs mediate anti-GBM therapeutic efficacy through the production of IFN-α, thus manipulation of pDCs constitutes an attractive new therapeutic target for the treatment of GBM. PMID:22952428

Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4+ Vα24 natural killer T cells expressing CD40L

PubMed Central

Nieda, M; Kikuchi, A; Nicol, A; Koezuka, Y; Ando, Y; Ishihara, S; Lapteva, N; Yabe, T; Tokunaga, K; Tadokoro, K; Juji, T

2001-01-01

Human Vα24 natural killer T (Vα24NKT) cells are activated by α-glycosylceramide-pulsed dendritic cells (DCs) in a CD1d-dependent and T-cell receptor-mediated manner. There are two major subpopulations of Vα24NKT cells, CD4– CD8– Vα24NKT and CD4+ Vα24NKT cells. We have recently shown that activated CD4– CD8– Vα24NKT cells have cytotoxic activity against DCs, but knowledge of the molecules responsible for cytotoxicity of Vα24NKT cells is currently limited. We aimed to investigate whether CD4+ Vα24NKT cells also have cytotoxic activity against DCs and to determine the mechanisms underlying any observed cytotoxic activity. We demonstrated that activated CD4+ Vα24NKT cells [CD40 ligand (CD40L) -positive] have cytotoxic activity against DCs (strongly CD40-positive), but not against monocytes (weakly CD40-positive) or phytohaemagglutinin blast T cells (CD40-negative), and that apoptosis of DCs significantly contributes to the observed cytotoxicity. The apoptosis of DCs following culture with activated CD4+ Vα24NKT cells, but not with resting CD4+ Vα24NKT cells (CD40L-negative), was partially inhibited by anti-CD40L mAb. Direct ligation of CD40 on the DCs by the anti-CD40 antibody also induced apoptosis of DCs. Our results suggest that CD40–CD40L interaction plays an important role in the induction of apoptosis of DCs following culture with activated CD4+ Vα24NKT cells. The apoptosis of DCs from normal donors, triggered by the CD40–CD40L interaction, may contribute to the homeostatic regulation of the normal human immune system, preventing the interminable activation of activated CD4+ Vα24NKT cells by virtue of apoptosis of DCs. PMID:11260318

DNA sensing via the Stimulator of Interferon Genes (STING) adaptor in myeloid dendritic cells induces potent tolerogenic responses1

PubMed Central

Huang, Lei; Li, Lingqian; Lemos, Henrique; Chandler, Phillip R.; Pacholczyk, Gabriela; Baban, Babak; Barber, Glen N.; Hayakawa, Yoshihiro; McGaha, Tracy L.; Ravishankar, Buvana; Munn, David H.; Mellor, Andrew L.

2013-01-01

Cytosolic DNA sensing via the STING adaptor incites autoimmunity by inducing type I IFN (IFNαβ). Here we show that DNA is also sensed via STING to suppress immunity by inducing indoleamine 2,3 dioxygenase (IDO). STING gene ablation abolished IFNαβ and IDO induction by dendritic cells (DCs) after DNA nanoparticle (DNP) treatment. Marginal zone macrophages, some DCs and myeloid cells ingested DNPs but CD11b+ DCs were the only cells to express IFNβ, while CD11b+ non-DCs were major IL-1β producers. STING ablation also abolished DNP-induced regulatory responses by DCs and regulatory T cells (Tregs), and hallmark regulatory responses to apoptotic cells were also abrogated. Moreover, systemic cyclic diguanylate monophosphate (c-diGMP) treatment to activate STING induced selective IFNβ expression by CD11b+ DCs and suppressed Th1 responses to immunization. Thus, previously unrecognized functional diversity amongst physiologic innate immune cells regarding DNA sensing via STING is pivotal in driving immune responses to DNA. PMID:23986532

Linking innate to adaptive immunity through dendritic cells.

PubMed

Steinman, Ralph M

2006-01-01

The function of dendritic cells (DCs) in linking innate to adaptive immunity is often summarized with two terms. DCs are sentinels, able to capture, process and present antigens and to migrate to lymphoid tissues to select rare, antigen-reactive T cell clones. DCs are also sensors, responding to a spectrum of environmental cues by extensive differentiation or maturation. The type of DC and the type of maturation induced by different stimuli influences the immunological outcome, such as the differentiation of Thl vs. Th2 T cells. Here we summarize the contributions of DCs to innate defences, particularly the production of immune enhancing cytokines and the activation of innate lymphocytes. Then we outline three innate features of DCs that influence peripheral tolerance and lead to adaptive immunity: a specialized endocytic system for antigen capture and processing, location and movements in vivo, and maturation in response to an array of stimuli. A new approach to the analysis of DC biology is to target antigens selectively to maturing DCs in vivo. This leads to stronger, more prolonged and broader (many immunogenic peptides) immunity by both T cells and B cells.

BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells.

PubMed

Combes, Alexis; Camosseto, Voahirana; N'Guessan, Prudence; Argüello, Rafael J; Mussard, Julie; Caux, Christophe; Bendriss-Vermare, Nathalie; Pierre, Philippe; Gatti, Evelina

2017-10-13

Toll-like receptors (TLR) are essential components of the innate immune system. Several accessory proteins, such as UNC93B1, are required for transport and activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1 + late endosomes in human plasmacytoid dendritic cells (pDC), leading to NF-κB activation and TNF production upon DNA detection. An inducible VAMP3 +/ LAMP2 +/ LAMP1 - endolysosome compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and consequent downstream signalling events. Conversely, sustained BAD-LAMP expression in pDCs contributes to their lack of type I interferon production after exposure to a TGF-β-positive microenvironment or isolation from human breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly, by promoting TLR9 sorting to late endosome compartments at steady state and in response to immunomodulatory cues.TLR9 is highly expressed by plasmacytoid dendritic cells and detects nucleic acids, but to discriminate between host and microbial nucleic acids TLR9 is sorted into different endosomal compartments. Here the authors show that BAD-LAMP limits type 1 interferon responses by sorting TLR9 to late endosomal compartments.

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

PubMed

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 difference (MD) -7.10 %, 95% confidence interval (CI -19.18 to 4.97; P = 0.25, I² = 21%, random-effects model). However, there was evidence of an effect on UPDRS part III motor subsection score at the end of the intervention phase (MD -14.43%, 95% CI -24.68 to -4.18; P = 0.006, I² = 2%, random-effects model; very low quality evidence). One study with 25 participants measured the reduction in off and on time with dyskinesia, but there was no evidence of an effect (MD 0.10 hours, 95% CI -0.14 to 0.34; P = 0.41, I² = 0%, random-effects model; and MD 0.00 hours, 95% CI -0.12 to 0.12; P = 1, I² = 0%, random- effects model, respectively; very low quality evidence).Two trials with a total of 41 participants measured gait speed using measures of timed gait at the end of the intervention phase, revealing no evidence of an effect ( standardised mean difference (SMD) 0.50, 95% CI -0.17 to 1.18; P = 0.14, I² = 11%, random-effects model; very low quality evidence). Another secondary outcome was health-related quality of life and we found one study with 25 participants reporting on the physical health and mental health aspects of health-related quality of life (MD 1.00 SF-12 score, 95% CI -5.20 to 7.20; I² = 0%, inverse variance method with random-effects model; very low quality evidence; and MD 1.60 SF-12 score, 95% CI -5.08 to 8.28; I² = 0%, inverse variance method with random-effects model; very low quality evidence, respectively). We found no study examining the effects of tDCS for improving activities of daily living. In two of six studies, dropouts , adverse events, or deaths occurring during the intervention phase were reported. There was insufficient evidence that dropouts , adverse effects, or deaths were higher with intervention (risk difference (RD) 0.04, 95% CI -0.05 to 0.12; P = 0.40, I² = 0%, random-effects model; very low quality evidence).We found one trial with a total of 16 participants examining the effects of tDCS plus movement therapy compared to control (sham tDCS) plus movement therapy on our secondary outcome, gait speed at the end of the intervention phase, revealing no evidence of an effect (MD 0.05 m/s, 95% CI -0.15 to 0.25; inverse variance method with random-effects model; very low quality evidence). We found no evidence of an effect regarding differences in dropouts and adverse effects between intervention and control groups (RD 0.00, 95% CI -0.21 to 0.21; Mantel-Haenszel method with random-effects model; very low quality evidence). There is insufficient evidence to determine the effects of tDCS for reducing off time ( when the symptoms are not controlled by the medication) and on time with dyskinesia ( time that symptoms are controlled but the person still experiences involuntary muscle movements ) , and for improving health- related quality of life, disability, and impairment in patients with IPD. Evidence of very low quality indicates no difference in dropouts and adverse events between tDCS and control groups.

Transcranial direct current stimulation improves neurorehabilitation of task-specific dystonia: a pilot study.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Alvaro

2014-03-01

Sensory-motor returning (SMR) can help the symptoms of task-specific focal hand dystonia. However, effects vary across patients and take many sessions. Here, we present proof of principle evidence that transcranial direct current stimulation (tDCS) can enhance these effects. We compared the effects of a combined tDCS-SMR protocol (n=4 patients) with the efficacy of SMR alone (n=30 patients). All 4 patients treated with the combined protocol showed greater improvement than those undergoing SMR alone. Results encourage a larger, parallel-group clinical trial with sham tDCS control.

A Proposed Study Program for the Enhancement of Performance of Clocks in the DCS Timing system.

DTIC Science & Technology

1982-08-31

INTRODUCTION This technical note presents a proposed program of test and analysis with 𔃾 a goal of using prediction techniques to enhance the...future digital DCS and methods of satisfying them so that the reader will understand: (1) what is needed from this program to enhance the performance...over a number of years, using both simulation and analysis , have recommended that all major nodes of the DCS be referenced to Coordinated Universal Time

Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

PubMed Central

Ilic, Nataša; Gruden-Movsesijan, Alisa; Cvetkovic, Jelena; Tomic, Sergej; Vucevic, Dragana Bozidar; Aranzamendi, Carmen; Colic, Miodrag; Pinelli, Elena; Sofronic-Milosavljevic, Ljiljana

2018-01-01

Trichinella spiralis, as well as its muscle larvae excretory–secretory products (ES L1), given either alone or via dendritic cells (DCs), induce a tolerogenic immune microenvironment in inbred rodents and successfully ameliorate experimental autoimmune encephalomyelitis. ES L1 directs the immunological balance away from T helper (Th)1, toward Th2 and regulatory responses by modulating DCs phenotype. The ultimate goal of our work is to find out if it is possible to translate knowledge obtained in animal model to humans and to generate human tolerogenic DCs suitable for therapy of autoimmune diseases through stimulation with ES L1. Here, the impact of ES L1 on the activation of human monocyte-derived DCs is explored for the first time. Under the influence of ES L1, DCs acquired tolerogenic (semi-matured) phenotype, characterized by low expression of HLA-DR, CD83, and CD86 as well as moderate expression of CD40, along with the unchanged production of interleukin (IL)-12 and elevated production of IL-10 and transforming growth factor (TGF)-β, compared to controls. The interaction with DCs involved toll-like receptors (TLR) 2 and 4, and this interaction was mainly responsible for the phenotypic and functional properties of ES L1-treated DCs. Importantly, ES L1 potentiated Th2 polarizing capacity of DCs, and impaired their allo-stimulatory and Th1/Th17 polarizing properties. Moreover, ES L1-treated DCs promoted the expansion of IL-10- and TGF-β- producing CD4+CD25hiFoxp3hi T cells in indolamine 2, 3 dioxygenase (IDO)-1-dependent manner and increased the suppressive potential of the primed T cell population. ES L1-treated DCs retained the tolerogenic properties, even after the challenge with different pro-inflammatory stimuli, including those acting via TLR3 and, especially TLR4. These results suggest that the induction of tolerogenic properties of DCs through stimulation with ES L1 could represent an innovative approach for the preparation of tolerogenic DC for treatment of inflammatory and autoimmune disorders. PMID:29416536

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

PubMed Central

Hung, Jinyi; Bauer, Ashley; Grossman, Murray; Hamilton, Roy H.; Coslett, H. B.; Reilly, Jamie

2017-01-01

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. PMID:28559805

Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS

PubMed Central

Prehn, Kristin; Flöel, Agnes

2015-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is increasingly used in research and clinical settings to enhance the effects of cognitive training. In our present review, we will first summarize studies using tDCS alone and in combination with cognitive training in older adults and patients with Alzheimer’s dementia (AD). We will also review one study (Meinzer et al., 2014c) that showed an improvement in cognitive performance during anodal tDCS over the left inferior frontal cortex in patients with mild cognitive impairment (MCI) which is regarded as a prodromal stage of AD. Although promising short-term results have been reported, evidence from randomized controlled trials (RCTs) with sufficient sample sizes is scarce. In addition, stimulation protocols (in terms of intensity, duration, and repetition of stimulation) that lead to sustained improvements in outcome measures relevant for daily life still remain to be established. Following, we will discuss modulating factors such as technical parameters as well as the question whether there are specific cognitive functions (e.g., learning, memory consolidation, executive control) which are more amenable to tDCS enhancement than others. Finally, we will highlight future directions and limitations in this field and emphasize the need to conduct RCTs to establish efficacy of interventions for activities of daily life for a given patient population. PMID:26441526

Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS.

PubMed

Prehn, Kristin; Flöel, Agnes

2015-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is increasingly used in research and clinical settings to enhance the effects of cognitive training. In our present review, we will first summarize studies using tDCS alone and in combination with cognitive training in older adults and patients with Alzheimer's dementia (AD). We will also review one study (Meinzer et al., 2014c) that showed an improvement in cognitive performance during anodal tDCS over the left inferior frontal cortex in patients with mild cognitive impairment (MCI) which is regarded as a prodromal stage of AD. Although promising short-term results have been reported, evidence from randomized controlled trials (RCTs) with sufficient sample sizes is scarce. In addition, stimulation protocols (in terms of intensity, duration, and repetition of stimulation) that lead to sustained improvements in outcome measures relevant for daily life still remain to be established. Following, we will discuss modulating factors such as technical parameters as well as the question whether there are specific cognitive functions (e.g., learning, memory consolidation, executive control) which are more amenable to tDCS enhancement than others. Finally, we will highlight future directions and limitations in this field and emphasize the need to conduct RCTs to establish efficacy of interventions for activities of daily life for a given patient population.

Positive effects of transcranial direct current stimulation in adult patients with attention-deficit/hyperactivity disorder - A pilot randomized controlled study.

PubMed

Cachoeira, Carolina Tosetto; Leffa, Douglas Teixeira; Mittelstadt, Suzana Doneda; Mendes, Lorenna Sena Teixeira; Brunoni, Andre R; Pinto, Jairo Vinicius; Blazius, Vtor; Machado, Vitoria; Bau, Claiton Henrique Dotto; Rohde, Luis Augusto; Grevet, Eugenio Horacio; Schestatsky, Pedro

2017-01-01

Almost 30% of adult patients with attention-deficit/hyperactivity disorder (ADHD) do not respond or tolerate standard pharmacological interventions. Few clinical investigations addressed the efficacy and tolerability of transcranial direct current stimulation (tDCS), a non-invasive neuromodulatory technique, in the disorder. We performed a double-blind, sham-controlled randomized clinical trial in 17 patients with ADHD. The set up for tDCS was the following: 2mA/20min/day for 5 days with the anode over the right dorsolateral prefrontal cortex and cathode over the left dorsolateral prefrontal cortex. ADHD symptoms were measured by the Adult ADHD Self-Report Scale (ASRS) and impairment with the Sheehan Disability Scale (SDS) in four different time points after stimulation. Participants achieved significant lower ASRS inattention and SDS scores after active tDCS in comparison with sham stimulation group. In addition, we detected a trend for a lower ASRS total score in the active tDCS group. Follow up data analysis revealed a positive interaction between time and treatment in both ASRS inattention, SDS and ASRS total scores. Short-term application of tDCS in adult patients with ADHD improved their symptoms, and this improvement persisted after the end of the stimulation. Future studies with larger sample sizes are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Failure To Recruit Anti-Inflammatory CD103+ Dendritic Cells and a Diminished CD4+ Foxp3+ Regulatory T Cell Pool in Mice That Display Excessive Lung Inflammation and Increased Susceptibility to Mycobacterium tuberculosis

PubMed Central

Leepiyasakulchai, Chaniya; Ignatowicz, Lech; Pawlowski, Andrzej; Källenius, Gunilla

2012-01-01

Susceptibility to Mycobacterium tuberculosis is characterized by excessive lung inflammation, tissue damage, and failure to control bacterial growth. To increase our understanding of mechanisms that may regulate the host immune response in the lungs, we characterized dendritic cells expressing CD103 (αE integrin) (αE-DCs) and CD4+ Foxp3+ regulatory T (Treg) cells during M. tuberculosis infection. In resistant C57BL/6 and BALB/c mice, the number of lung αE-DCs increased dramatically during M. tuberculosis infection. In contrast, highly susceptible DBA/2 mice failed to recruit αE-DCs even during chronic infection. Even though tumor necrosis factor alpha (TNF-α) is produced by multiple DCs and macrophage subsets and is required for control of bacterial growth, αE-DCs remained TNF-α negative. Instead, αE-DCs contained a high number of transforming growth factor beta-producing cells in infected mice. Further, we show that Treg cells in C57BL/6 and DBA/2 mice induce gamma interferon during pulmonary tuberculosis. In contrast to resistant mice, the Treg cell population was diminished in the lungs, but not in the draining pulmonary lymph nodes (PLN), of highly susceptible mice during chronic infection. Treg cells have been reported to inhibit M. tuberculosis-specific T cell immunity, leading to increased bacterial growth. Still, despite the reduced number of lung Treg cells in DBA/2 mice, the bacterial load in the lungs was increased compared to resistant animals. Our results show that αE-DCs and Treg cells that may regulate the host immune response are increased in M. tuberculosis-infected lungs of resistant mice but diminished in infected lungs of susceptible mice. PMID:22215739

Spreading Effect of tDCS in Individuals with Attention-Deficit/Hyperactivity Disorder as Shown by Functional Cortical Networks: A Randomized, Double-Blind, Sham-Controlled Trial.

PubMed

Cosmo, Camila; Ferreira, Cândida; Miranda, José Garcia Vivas; do Rosário, Raphael Silva; Baptista, Abrahão Fontes; Montoya, Pedro; de Sena, Eduardo Pondé

2015-01-01

Transcranial direct current stimulation (tDCS) is known to modulate spontaneous neural network excitability. The cognitive improvement observed in previous trials raises the potential of this technique as a possible therapeutic tool for use in attention-deficit/hyperactivity disorder (ADHD) population. However, to explore the potential of this technique as a treatment approach, the functional parameters of brain connectivity and the extent of its effects need to be more fully investigated. The aim of this study was to investigate a functional cortical network (FCN) model based on electroencephalographic activity for studying the dynamic patterns of brain connectivity modulated by tDCS and the distribution of its effects in individuals with ADHD. Sixty ADHD patients participated in a parallel, randomized, double-blind, sham-controlled trial. Individuals underwent a single session of sham or anodal tDCS at 1 mA of current intensity over the left dorsolateral prefrontal cortex for 20 min. The acute effects of stimulation on brain connectivity were assessed using the FCN model based on electroencephalography activity. Comparing the weighted node degree within groups prior to and following the intervention, a statistically significant difference was found in the electrodes located on the target and correlated areas in the active group (p < 0.05), while no statistically significant results were found in the sham group (p ≥ 0.05; paired-sample Wilcoxon signed-rank test). Anodal tDCS increased functional brain connectivity in individuals with ADHD compared to data recorded in the baseline resting state. In addition, although some studies have suggested that the effects of tDCS are selective, the present findings show that its modulatory activity spreads. Further studies need to be performed to investigate the dynamic patterns and physiological mechanisms underlying the modulatory effects of tDCS. ClinicalTrials.gov NCT01968512.

Engaging the CD40-CD40L pathway augments T-helper cell responses and improves control of Mycobacterium tuberculosis infection

PubMed Central

Bizzell, Erica; Madan-Lala, Ranjna

2017-01-01

Mycobacterium tuberculosis (Mtb) impairs dendritic cell (DC) functions and induces suboptimal antigen-specific CD4 T cell immune responses that are poorly protective. Mucosal T-helper cells producing IFN-γ (Th1) and IL-17 (Th17) are important for protecting against tuberculosis (TB), but the mechanisms by which DCs generate antigen-specific T-helper responses during Mtb infection are not well defined. We previously reported that Mtb impairs CD40 expression on DCs and restricts Th1 and Th17 responses. We now demonstrate that CD40-dependent costimulation is required to generate IL-17 responses to Mtb. CD40-deficient DCs were unable to induce antigen-specific IL-17 responses after Mtb infection despite the production of Th17-polarizing innate cytokines. Disrupting the interaction between CD40 on DCs and its ligand CD40L on antigen-specific CD4 T cells, genetically or via antibody blockade, significantly reduced antigen-specific IL-17 responses. Importantly, engaging CD40 on DCs with a multimeric CD40 agonist (CD40LT) enhanced antigen-specific IL-17 generation in ex vivo DC-T cell co-culture assays. Further, intratracheal instillation of Mtb-infected DCs treated with CD40LT significantly augmented antigen-specific Th17 responses in vivo in the lungs and lung-draining lymph nodes of mice. Finally, we show that boosting CD40-CD40L interactions promoted balanced Th1/Th17 responses in a setting of mucosal DC transfer, and conferred enhanced control of lung bacterial burdens following aerosol challenge with Mtb. Our results demonstrate that CD40 costimulation by DCs plays an important role in generating antigen-specific Th17 cells and targeting the CD40-CD40L pathway represents a novel strategy to improve adaptive immunity to TB. PMID:28767735

Joint Optimization of Distribution Network Design and Two-Echelon Inventory Control with Stochastic Demand and CO2 Emission Tax Charges

PubMed Central

Li, Shuangyan; Li, Xialian; Zhang, Dezhi; Zhou, Lingyun

2017-01-01

This study develops an optimization model to integrate facility location and inventory control for a three-level distribution network consisting of a supplier, multiple distribution centers (DCs), and multiple retailers. The integrated model addressed in this study simultaneously determines three types of decisions: (1) facility location (optimal number, location, and size of DCs); (2) allocation (assignment of suppliers to located DCs and retailers to located DCs, and corresponding optimal transport mode choices); and (3) inventory control decisions on order quantities, reorder points, and amount of safety stock at each retailer and opened DC. A mixed-integer programming model is presented, which considers the carbon emission taxes, multiple transport modes, stochastic demand, and replenishment lead time. The goal is to minimize the total cost, which covers the fixed costs of logistics facilities, inventory, transportation, and CO2 emission tax charges. The aforementioned optimal model was solved using commercial software LINGO 11. A numerical example is provided to illustrate the applications of the proposed model. The findings show that carbon emission taxes can significantly affect the supply chain structure, inventory level, and carbon emission reduction levels. The delay rate directly affects the replenishment decision of a retailer. PMID:28103246

The relative risk of decompression sickness during and after air travel following diving.

PubMed

Freiberger, J J; Denoble, P J; Pieper, C F; Uguccioni, D M; Pollock, N W; Vann, R D

2002-10-01

Decompression sickness (DCS) can be provoked by post-dive flying but few data exist to quantify the risk of different post-dive, preflight surface intervals (PFSI). We conducted a case-control study using field data from the Divers Alert Network to evaluate the relative risk of DCS from flying after diving. The PFSI and the maximum depths on the last day of diving (MDLD) were analyzed from 627 recreational dive profiles. The data were divided into quartiles based on surface interval and depth. Injured divers (cases) and uninjured divers (controls) were compared using logistic regression to determine the association of DCS with time and depth while controlling for diver and dive profiles characteristics. These included PFSI, MDLD, gender, height, weight, age, and days of diving. The means (+/-SD) for cases and controls were as follows: PFSI, 20.7 +/- 9.6 h vs. 27.1 +/- 6.7 h; MDLD, 22.5 +/- 14 meters sea water (msw) vs. 19 +/- 11.3 msw; male gender, 60% vs. 70%; weight, 75.8 +/- 18 kg vs. 77.6 +/- 16 kg; height, 173 +/- 16 cm vs. 177 +/- 9 cm; age, 36.8 +/- 10 yr vs. 42.9 +/- 11 yr; diving > or = 3 d, 58% vs. 97%. Relative to flying > 28 h after diving, the odds of DCS (95% CI) were: 1.02 (0.61, 1.7) 24-28 h; 1.84 (1.0, 3.3) 20-24 h; and 8.5 (3.85, 18.9) < 20 h. Relative to a depth of < 14.7 msw, the odds of DCS (95% CI) were: 1.2 (0.6, 1.7) 14.7-18.5 msw; 2.9 (1.65, 5.3) 18.5-26 msw; and 5.5 (2.96, 1 0.0) > 26 msw. Odds ratios approximate relative risk in rare diseases such as DCS. This study demonstrated an increase in relative risk from flying after diving following shorter PFSIs and/or greater dive depths on the last day. The relative risk increases geometrically as the PFSI becomes smaller.

[Dopamine receptor signaling regulates human osteoclastogenesis].

PubMed

Hanami, Kentaro; Nakano, Kazuhisa; Tanaka, Yoshiya

2013-01-01

Although the central nervous system and the neurotransmitters are known to control not only the immune system but also the homeostasis of bone mass, their pathological relevance to bone disorders remains unclear. Osteoclasts in the synovium of rheumatoid arthritis (RA) play an important role in bone destruction. It is known that increased sympathetic nervous activity increases both differentiation and function of osteoclasts, which leads to bone loss. Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. We previously reported that dopamine plays an important role in IL-6-IL-17 axis and subsequent joint destruction in RA. The major source of dopamine in the synovial tissue of RA was dendritic cells (DCs) that stored and secreted dopamine. Dopamine released by DCs bounded to D1-like dopamine receptors on T cells and induced activation of cAMP and differentiation to Th17 cells via IL-6 production We here overview the interplay among the immune system, bone metabolism and neurologic system shedding light upon dopaminergic signals upon osteoclastogenesis.

Recent trends in workload, input costs, and expenditures in the Air Force Medical Service Direct Care System.

PubMed

Robbins, Anthony S; Moilanen, Dale A; Fonseca, Vincent P; Chao, Susan Y

2002-04-01

A study was conducted to examine the relationship between two types of trends in the Air Force Medical Service Direct Care System (AFMS/DCS): trends in expenditures, total and by categories; and trends in medical workload, defined as the sum of inpatient admissions and outpatient clinic visits. Expenditure and medical workload data were extracted from the Medical Expense and Performance Reporting System Executive Query System. Medical inflation data were obtained from the Bureau of Labor Statistics Producer Price Index series. Between fiscal years 1995 and 1999, the AFMS/DCS experienced a 21.2% decrease in medical workload, but total (nominal) expenditures declined only 3.6%. Of all expenditure categories, only inpatient medical care, outpatient medical care, and military-funded private sector care for active duty personnel (supplemental care) have any direct relationship with AFMS/DCS medical workload. Real expenditures for the three categories above decreased by 20.3% during the 5-year period. Accounting for inflation and considering only expenditures related to medical workload, these results suggest that the AFMS/DCS is spending approximately 20% less money to do approximately 20% less work.

Central nervous system decompression sickness and venous gas emboli in hypobaric conditions.

PubMed

Balldin, Ulf I; Pilmanis, Andrew A; Webb, James T

2004-11-01

Altitude decompression sickness (DCS) that involves the central nervous system (CNS) is a rare but potentially serious condition. Identification of early symptoms and signs of this condition might improve treatment. We studied data from 26 protocols carried out in our laboratory over the period 1983-2003; all were designed to provoke DCS in a substantial proportion of subjects. The data set included 2843 cases. We classified subject-exposures that resulted in DCS as: 1) neurological DCS of peripheral and/or central origin (NEURO); 2) a subset of those that involved only the CNS (CNS); and 3) all other cases, i.e., DCS cases that did not have a neurological component (OTHER). For each case, echo imaging data were used to document whether venous gas emboli (VGE) were present, and their level was classified as: 1) any level, i.e., Grade 1 or higher (VGE-1); and 2) high level, Grade 4 (VGE-4). There were 1108 cases of altitude DCS in the database; 218 were classified as NEURO and 49 of those as CNS. VGE-1 were recorded in 83.8% of OTHER compared with 58.7% of NEURO and 55.1% of CNS (both p < 0.001 compared with OTHER). The corresponding values for VGE-4 were 48.8%, 37.0%, and 34.7% (p < 0.001, compared to OTHER). Hyperbaric oxygen (HBO) was used to treat about half of the CNS cases, while all other cases were treated with 2 h breathing 100% oxygen at ground level. Since only about half of the rare cases of hypobaric CNS DCS cases were accompanied by any level of VGE, echo imaging for bubbles may have limited application for use as a predictor of such cases.

The Effect of D-cycloserine on Subliminal Cue Exposure in Spider Fearful Individuals

PubMed Central

Gutner, Cassidy A.; Weinberger, Joel; Hofmann, Stefan G.

2012-01-01

Research on d-cycloserine (DCS) has demonstrated a significant effect on symptom reduction in human studies that utilized conventional exposure-based approaches. Recent studies have offered promising results for targeting fears through subliminal paradigms. In this double-blind, randomized placebo controlled study, 45 spider fearful individuals received DCS or placebo pills prior to completing a subliminal cue exposure task to images of spiders. Participants completed self-report questionnaires and a behavioral approach task to a live caged tarantula. After repeated exposure to subliminal spider cues, participants in the DCS group reported a greater reduction in disgust than individuals in the placebo group. No difference was observed in fear ratings. These findings suggest that DCS augments the reduction in disgust in spider fearful subjects after subliminal exposure to spider cues. PMID:22992160

Neuromodulation directed at the prefrontal cortex of subjects with obesity reduces snack food intake and hunger in a randomized trial.

PubMed

Heinitz, Sascha; Reinhardt, Martin; Piaggi, Paolo; Weise, Christopher M; Diaz, Enrique; Stinson, Emma J; Venti, Colleen; Votruba, Susanne B; Wassermann, Eric M; Alonso-Alonso, Miguel; Krakoff, Jonathan; Gluck, Marci E

2017-12-01

Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity. Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake-related appetite ratings in individuals with obesity. Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m 2 ): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables. Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more ( P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals ( P = 0.01), after long-term tDCS. Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. This trial was registered at clinicaltrials.gov as NCT00739362. © 2017 American Society for Nutrition.

OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury.

PubMed

Fazal, Nadeem

2013-01-01

Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury.

OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury☆

PubMed Central

Fazal, Nadeem

2013-01-01

Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury. PMID:24600560

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

PubMed

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.

Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization

PubMed Central

Nakamoto, Y; Mizukoshi, E; Kitahara, M; Arihara, F; Sakai, Y; Kakinoki, K; Fujita, Y; Marukawa, Y; Arai, K; Yamashita, T; Mukaida, N; Matsushima, K; Matsui, O; Kaneko, S

2011-01-01

Despite curative locoregional treatments for hepatocellular carcinoma (HCC), tumour recurrence rates remain high. The current study was designed to assess the safety and bioactivity of infusion of dendritic cells (DCs) stimulated with OK432, a streptococcus-derived anti-cancer immunotherapeutic agent, into tumour tissues following transcatheter hepatic arterial embolization (TAE) treatment in patients with HCC. DCs were derived from peripheral blood monocytes of patients with hepatitis C virus-related cirrhosis and HCC in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor and stimulated with 0·1 KE/ml OK432 for 2 days. Thirteen patients were administered with 5 × 106 of DCs through arterial catheter during the procedures of TAE treatment on day 7. The immunomodulatory effects and clinical responses were evaluated in comparison with a group of 22 historical controls treated with TAE but without DC transfer. OK432 stimulation of immature DCs promoted their maturation towards cells with activated phenotypes, high expression of a homing receptor, fairly well-preserved phagocytic capacity, greatly enhanced cytokine production and effective tumoricidal activity. Administration of OK432-stimulated DCs to patients was found to be feasible and safe. Kaplan–Meier analysis revealed prolonged recurrence-free survival of patients treated in this manner compared with the historical controls (P = 0·046, log-rank test). The bioactivity of the transferred DCs was reflected in higher serum concentrations of the cytokines IL-9, IL-15 and tumour necrosis factor-α and the chemokines CCL4 and CCL11. Collectively, this study suggests that a DC-based, active immunotherapeutic strategy in combination with locoregional treatments exerts beneficial anti-tumour effects against liver cancer. PMID:21087443

Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

PubMed

Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

2016-06-01

No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

[The influence of mycophenolate mofetil upon the maturation and allostimulatory activity of cultured dendritic cell progenitors and the effects of tolerance induction in allograft recipients].

PubMed

Han, Cong-hui; Li, Huai-fu; Wang, Yu-xin; Zhang, Ming; Wang, Yin; Yin, Ming; Min, Zhi-lian; Zheng, Ke-li

2005-05-25

To investigate the influence of mycophenolate mofetil (MMF) on the maturation and allostimulatory activity of cultured dendritic cell progenitors (DCPs) and to evaluate the efficacy of pretreatment of donor dendritic cells (DCs) with MMF in tolerance induction in allograft recipients and its possible mechanism. DCPs of Balb/c mice were cultured in culture fluid containing recombinant mouse granulocyte-macrophage colony stimulating factor (GM-CSF), and then divided into 4 groups: control group, MMF group, lipopolysaccharide (LPS) group, and MMF + LPS group. Seven days later, flow cytometry was used to analyze the phenotypes of the DCs. ELISA was used to examine the level of IL-12 in the supernatant. T cells from the spleens of C57/BL6 mice were cultured together with inactivated DCs from Balb/c mice, and added with [(3)H]-TdR. Mixed lymphocyte reaction (MLR) was analyzed. The DCs and MMF-DCs cultured for 5 days were co-cultured with T hybridoma cells of the line MF2.2D9 in culture fluid containing ovalbumin (OVA). Twenty-four hours later, the supernatant was collected and ELISA was used to measure the level of interleukin (IL)-12 so as to reflect the antigen-presenting ability of the DCs. OVA immunized C57/BL6 mice for 4 times. 21 days after T cells were collected from the spleens and co-incubated with DCs and MMF-DCs, [(3)H]-TdR was added and the values of counts per minute (cpm) were calculated so as to analyze the antigen-specific proliferation. Twenty-four Balb/c mice were randomly divided into 3 groups: group A (without treatment), group B (treatment with intravenous injection of untreated DCs of Balb/c mice), and group C (treatment with intravenous injection of DCs of Balb/c mice treated with MMF), and then transplanted with the hearts of C57/BL6 mice. The functions of the transplanted hearts were evaluated by touching the arterial pulse and histological examination. ELISA was used to detect the levels of Th1 cytokines, such as IL-12, IL-4, IL-10, IL-2, and IFN-gamma, in the cultured DCs and in the sera of the recipients 7 and 14 days after culture or transplantation. The immunophenotypic analysis showed that in comparison with those in the control group and the LPS group the expressions of the costimulatory molecules, Ia(d), CD80, and CD86, of the DCPs were significantly weaker in the MMF-group and MMP + LPS group. The IL-12 levels in the supernatant of the MMF and MMF + LPS groups of DCPs were significantly lower than those in the other groups (P < 0.01). The IL-12 level of the MF2.2D9 cells treated with MMF-treated DCs was significantly lower than control group (P < 0.01). The ability to stimulate proliferation of T cells of the same genotype in the MMF-DC group was significantly inhibited (P < 0.01). The survival time of the transplanted heart was 30.50 +/- 3.25 days in the C57/BL6 mice injected with untreated DCPs of Balb/c mice (21.25 +/- 2.12, P < 0.01) and that in the control C57/BL6 mice (8.63 +/- 1.06 days, P < 0.01) and with a significant difference between the latter 2 groups too (P < 0.01). The levels of, such as IL-2 and IFN-gamma, 7 and 14 days after heart transplantation of the group B were all significantly lower than those of the group A (both P < 0.05). The IL-2 and IFN-gamma levels 7 days after the heart transplantation were similar to those in the group B (both P > 0.05) and even lower than those of the group C (both P < 0.05). The IL-10 level in the groups B and C were all higher than those in the group A (all P < 0.05) with a significant difference between the group B and group C. The level of IL-4 was not significantly different among the 3 groups. MMF has a significant suppressive effect on the maturation and function of DCs, which leads to a donor-specific tolerance in transplant recipients.

Harnessing dendritic cells in inflammatory skin diseases.

PubMed

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

2011-02-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Three-dimensional culture and interaction of cancer cells and dendritic cells in an electrospun nano-submicron hybrid fibrous scaffold

PubMed Central

Kim, Tae-Eon; Kim, Chang Gun; Kim, Jin Soo; Jin, Songwan; Yoon, Sik; Bae, Hae-Rahn; Kim, Jeong-Hwa; Jeong, Young Hun; Kwak, Jong-Young

2016-01-01

An artificial three-dimensional (3D) culture system that mimics the tumor microenvironment in vitro is an essential tool for investigating the cross-talk between immune and cancer cells in tumors. In this study, we developed a 3D culture system using an electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffold (NFS). A hybrid NFS containing an uninterrupted network of nano- and submicron-scale fibers (400 nm to 2 µm) was generated by deposition onto a stainless steel mesh instead of an aluminum plate. The hybrid NFS contained multiplanar pores in a 3D structure. Surface-seeded mouse CT26 colon cancer cells and bone marrow-derived dendritic cells (BM-DCs) were able to infiltrate the hybrid NFS within several hours. BM-DCs cultured on PCL nanofibers showed a baseline inactive form, and lipopolysaccharide (LPS)-activated BM-DCs showed increased expression of CD86 and major histocompatibility complex Class II. Actin and phosphorylated FAK were enriched where unstimulated and LPS-stimulated BM-DCs contacted the fibers in the 3D hybrid NFS. When BM-DCs were cocultured with mitoxantrone-treated CT26 cells in a 3D hybrid NFS, BM-DCs sprouted cytoplasm to, migrated to, synapsed with, and engulfed mitoxantrone-treated CT26 cancer cells, which were similar to the naturally occurring cross-talk between these two types of cells. The 3D hybrid NFS developed here provides a 3D structure for coculture of cancer and immune cells. PMID:27042051

Three-dimensional culture and interaction of cancer cells and dendritic cells in an electrospun nano-submicron hybrid fibrous scaffold.

PubMed

Kim, Tae-Eon; Kim, Chang Gun; Kim, Jin Soo; Jin, Songwan; Yoon, Sik; Bae, Hae-Rahn; Kim, Jeong-Hwa; Jeong, Young Hun; Kwak, Jong-Young

2016-01-01

An artificial three-dimensional (3D) culture system that mimics the tumor microenvironment in vitro is an essential tool for investigating the cross-talk between immune and cancer cells in tumors. In this study, we developed a 3D culture system using an electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffold (NFS). A hybrid NFS containing an uninterrupted network of nano- and submicron-scale fibers (400 nm to 2 µm) was generated by deposition onto a stainless steel mesh instead of an aluminum plate. The hybrid NFS contained multiplanar pores in a 3D structure. Surface-seeded mouse CT26 colon cancer cells and bone marrow-derived dendritic cells (BM-DCs) were able to infiltrate the hybrid NFS within several hours. BM-DCs cultured on PCL nanofibers showed a baseline inactive form, and lipopolysaccharide (LPS)-activated BM-DCs showed increased expression of CD86 and major histocompatibility complex Class II. Actin and phosphorylated FAK were enriched where unstimulated and LPS-stimulated BM-DCs contacted the fibers in the 3D hybrid NFS. When BM-DCs were cocultured with mitoxantrone-treated CT26 cells in a 3D hybrid NFS, BM-DCs sprouted cytoplasm to, migrated to, synapsed with, and engulfed mitoxantrone-treated CT26 cancer cells, which were similar to the naturally occurring cross-talk between these two types of cells. The 3D hybrid NFS developed here provides a 3D structure for coculture of cancer and immune cells.

The use of the LANDSAT data collection system and imagery in reservoir management and operation. [Maine, Vermont, New Hamphire, Canada, St. John River, Beech Ridge, Merrimack River, and Franklin Falls

NASA Technical Reports Server (NTRS)

Cooper, S. (Principal Investigator); Buckelew, T. D.; Mckim, H. L.; Merry, C. J.

1977-01-01

The author has identified the following significant results. An increase in the data collection system's (DCS) ability to function in the flood control mission with no additional manpower was demonstrated during the storms which struck New England during April and May of 1975 and August 1976. It was found that for this watershed, creditable flood hydrographs could be generated from DCS data. It was concluded that an ideal DCS for reservoir regulation would draw features from LANDSAT and GOES. MSS grayscale computer printout and a USGS topographic map were compared, yielding an optimum computer classification map of the wetland areas of the Merrimack River estuary. A classification accuracy of 75% was obtained for the wetlands unit, taking into account the misclassified and the unclassified pixels. The MSS band 7 grayscale printouts of the Franklin Falls reservoir showed good agreement to USGS topographic maps in total area of water depicted at the low water reservoir stage and at the maximum inundation level. Preliminary analysis of the LANDSAT digital data using the GISS computer algorithms showed that the radiance of snow cover/vegetation varied from approximately 20 mW/sq cm sr in nonvegetated areas to less than 4 mW/sq cm sr for densely covered forested area.

TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns

PubMed Central

Cardoso, Elaine Cristina; Pereira, Nátalli Zanete; Mitsunari, Gabrielle Eimi; Oliveira, Luanda Mara da Silva; Ruocco, Rosa Maria S. A.; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo; da Silva Duarte, Alberto José; Sato, Maria Notomi

2013-01-01

Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity. PMID:23826189

TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.

PubMed

Cardoso, Elaine Cristina; Pereira, Nátalli Zanete; Mitsunari, Gabrielle Eimi; Oliveira, Luanda Mara da Silva; Ruocco, Rosa Maria S A; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo; da Silva Duarte, Alberto José; Sato, Maria Notomi

2013-01-01

Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity.

Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

PubMed

Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

2013-04-01

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.

Sphingosine 1-Phosphate- and C-C Chemokine Receptor 2-Dependent Activation of CD4+ Plasmacytoid Dendritic Cells in the Bone Marrow Contributes to Signs of Sepsis-Induced Immunosuppression

PubMed Central

Smirnov, Anna; Pohlmann, Stephanie; Nehring, Melanie; Ali, Shafaqat; Mann-Nüttel, Ritu; Scheu, Stefanie; Antoni, Anne-Charlotte; Hansen, Wiebke; Büettner, Manuela; Gardiasch, Miriam J.; Westendorf, Astrid M.; Wirsdörfer, Florian; Pastille, Eva; Dudda, Marcel; Flohé, Stefanie B.

2017-01-01

Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis. Bone marrow cells (BMC) were isolated after sham or CLP operation, the cellular composition was analyzed, and bone marrow-derived DCs (BMDCs) were generated in vitro. From 24 h on after CLP, BMC gave rise to BMDC that released enhanced levels of IL-10. In parallel, a population of CD11chiMHCII+CD4+ DCs expanded in the bone marrow in a MyD88-dependent manner. Prior depletion of the CD11chiMHCII+CD4+ DCs from BMC in vitro reversed the increased IL-10 secretion of subsequently differentiating BMDC. The expansion of the CD11chiMHCII+CD4+ DC population in the bone marrow after CLP required the function of sphingosine 1-phosphate receptors and C-C chemokine receptor (CCR) 2, the receptor for C-C chemokine ligand (CCL) 2, but was not associated with monocyte mobilization. CD11chiMHCII+CD4+ DCs were identified as plasmacytoid DCs (pDCs) that had acquired an activated phenotype according to their increased expression of MHC class II and CD86. A redistribution of CD4+ pDCs from MHC class II− to MHC class II+ cells concomitant with enhanced expression of CD11c finally led to the rise in the number of CD11chiMHCII+CD4+ DCs. Enhanced levels of CCL2 were found in the bone marrow of septic mice and the inhibition of CCR2 dampened the expression of CD86 on CD4+ pDCs after CLP in vitro. Depletion of pDCs reversed the bias of splenic DCs toward increased IL-10 synthesis after CLP in vivo. Thus, during polymicrobial sepsis, CD4+ pDCs are activated in the bone marrow and induce functional reprogramming of differentiating BMDC toward an immunosuppressive phenotype. PMID:29218051

Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

PubMed Central

Spiegel, Daniel P.; Hansen, Bruce C.; Byblow, Winston D.; Thompson, Benjamin

2012-01-01

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex. PMID:22563485

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

PubMed

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

PubMed Central

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P.; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M.; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders. PMID:28861085

Anodal tDCS to V1 blocks visual perceptual learning consolidation.

PubMed

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.

Sex Mediates the Effects of High-Definition Transcranial Direct Current Stimulation on "Mind-Reading".

PubMed

Martin, A K; Huang, J; Hunold, A; Meinzer, M

2017-12-16

Sex differences in social cognitive ability are well established, including measures of Theory of Mind (ToM). The aim of this study was to investigate if sex mediates the effects of high-definition transcranial direct current stimulation (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty healthy young adults (18-35 years) were randomly allocated to receive either anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. In each of the two sessions, subjects completed the RMET. Anodal stimulation to the dmPFC increased accuracy on the RMET in females only. To assure regional specificity we performed a follow-up study stimulating the right temporoparietal junction and found no effect in either sex. The current study is the first to show improved performance on the RMET after tDCS to the dmPFC in females only. The polarity-specific effects and use of focal HD-tDCS provide evidence for sex-dependent differences in dmPFC function in relation to the RMET. Future studies using tDCS to study or improve ToM, need to consider sex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of pore size of three-dimensionally ordered macroporous chitosan-silica matrix on solubility, drug release, and oral bioavailability of loaded-nimodipine.

PubMed

Gao, Yikun; Xie, Yuling; Sun, Hongrui; Zhao, Qinfu; Zheng, Xin; Wang, Siling; Jiang, Tongying

2016-01-01

To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan-silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug. 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated. With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively. Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.

Modulating behavioral inhibition by tDCS combined with cognitive training.

PubMed

Ditye, Thomas; Jacobson, Liron; Walsh, Vincent; Lavidor, Michal

2012-06-01

Cognitive training is an effective tool to improve a variety of cognitive functions, and a small number of studies have now shown that brain stimulation accompanying these training protocols can enhance their effects. In the domain of behavioral inhibition, little is known about how training can affect this skill. As for transcranial direct current stimulation (tDCS), it was previously found that stimulation over the right inferior frontal gyrus (rIFG) facilitates behavioral inhibition performance and modulates its electrophysiological correlates. This study aimed to investigate this behavioral facilitation in the context of a learning paradigm by giving tDCS over rIFG repetitively over four consecutive days of training on a behavioral inhibition task (stop signal task (SST)). Twenty-two participants took part; ten participants were assigned to receive anodal tDCS (1.5 mA, 15 min), 12 were assigned to receive training but not active stimulation. There was a significant effect of training on learning and performance in the SST, and the integration of the training and rIFG-tDCS produced a more linear learning slope. Better performance was also found in the active stimulation group. Our findings show that tDCS-combined cognitive training is an effective tool for improving the ability to inhibit responses. The current study could constitute a step toward the use of tDCS and cognitive training as a therapeutic tool for cognitive control impairments in conditions such as attention-deficit hyperactivity disorder (ADHD) or schizophrenia.

Transcranial direct current stimulation improves clinical symptoms in adolescents with attention deficit hyperactivity disorder.

PubMed

Soff, Cornelia; Sotnikova, Anna; Christiansen, Hanna; Becker, Katja; Siniatchkin, Michael

2017-01-01

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has repeatedly been shown to improve working memory. As patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in working memory that correlate with clinical symptoms, it is hypothesized that the modulation of prefrontal activity with tDCS in patients with ADHD increases performance in working memory and reduces symptoms of ADHD. To test this hypothesis, fifteen adolescents with ADHD (12-16 years old, three girls and 12 boys) were treated according to the randomized, double-blinded, sham-controlled, crossover design with either 1 mA anodal tDCS over the left dorsolateral prefrontal cortex or with the sham protocol 5 days each with a 2 weeks pause between these conditions. Anodal tDCS caused a significant reduction in clinical symptoms of inattention and impulsivity in adolescents with ADHD compared to sham stimulation. The clinical effects were supported by a significant reduction in inattention and hyperactivity in a standardized working memory test (QbTest). The described effects were more pronounced 7 days after the end of stimulation, a fact which emphasizes the long-lasting clinical and neuropsychological changes after tDCS. This study provides the first evidence that tDCS may reduce symptoms of ADHD and improve neuropsychological functioning in adolescents and points on the potential of tDCS as a form of treatment for ADHD.

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

PubMed

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.

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

PubMed

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.

Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia.

PubMed

Benussi, Alberto; Dell'Era, Valentina; Cotelli, Maria Sofia; Turla, Marinella; Casali, Carlo; Padovani, Alessandro; Borroni, Barbara

Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present study investigated whether a two-weeks' treatment with cerebellar anodal tDCS could improve symptoms in patients with neurodegenerative cerebellar ataxia and could modulate cerebello-motor connectivity, at short and long term. We performed a double-blind, randomized, sham controlled trial with cerebellar tDCS (5 days/week for 2 weeks) in twenty patients with ataxia. Each patient underwent a clinical evaluation pre- and post-anodal tDCS or sham stimulation. A follow-up evaluation was performed at one and three months. Cerebello-motor connectivity was evaluated using transcranial magnetic stimulation (TMS) at baseline and at follow-up. Patients who underwent anodal tDCS showed a significant improvement in all performance scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale, 9-hole peg test, 8-m walking time) and in cerebellar brain inhibition compared to patients who underwent sham stimulation. A two-weeks' treatment with anodal cerebellar tDCS improves symptoms in patients with ataxia and restores physiological cerebellar brain inhibition pathways. Cerebellar tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia. Copyright © 2016 Elsevier Inc. All rights reserved.

A correlation of measles specific antibodies and the number of plasmacytoid dendritic cells is observed after measles vaccination in 9 month old infants

PubMed Central

García-León, Miguel L; Bonifaz, Laura C; Espinosa-Torres, Bogart; Hernández-Pérez, Brenda; Cardiel-Marmolejo, Lino; Santos-Preciado, José I; Wong-Chew, Rosa M

2015-01-01

Measles virus (MeV) represents one of the main causes of death among young children, particularly in developing countries. Upon infection, MeV controls both interferon induction (IFN) and the interferon signaling pathway which results in a severe host immunosuppression that can persists for up to 6 mo after infection. Despite the global biology of MeV infection is well studied, the role of the plasmacytoid dendritic cells (pDCs) during the host innate immune response after measles vaccination remains largely uncharacterized. Here we investigated the role of pDCs, the major producers of interferon in response to viral infections, in the development of adaptive immune response against MeV vaccine. We report that there is a strong correlation between pDCs population and the humoral immune response to Edmonston Zagreb (EZ) measles vaccination in 9-month-old mexican infants. Five infants were further evaluated after vaccination, showing a clear increase in pDCs at baseline, one week and 3 months after immunization. Three months postvaccination they showed increase in memory T-cells and pDCs populations, high induction of adaptive immunity and also observed a correlation between pDCs number and the humoral immune response. These findings suggest that the development and magnitude of the adaptive immune response following measles immunization is directly dependent on the number of pDCs of the innate immune response. PMID:26075901

Does d-Cycloserine Augmentation of CBT Improve Therapeutic Homework Compliance for Pediatric Obsessive-Compulsive Disorder?

PubMed

Park, Jennifer M; Small, Brent J; Geller, Daniel A; Murphy, Tanya K; Lewin, Adam B; Storch, Eric A

2014-07-01

Clinical studies in adults and children with obsessive-compulsive disorder (OCD) have shown that d-cycloserine (DCS) can improve treatment response by enhancing fear extinction learning during exposure-based psychotherapy. Some have hypothesized that improved treatment response is a function of increased compliance and engagement in therapeutic homework tasks, a core component of behavioral treatment. The present study examined the relationship between DCS augmented cognitive-behavioral therapy (CBT) and homework compliance in a double-blind, placebo controlled trial with 30 youth with OCD. All children received 10 CBT sessions, the last seven of which included exposure and response prevention paired with DCS or placebo dosed 1 h before the session started. Results suggested that DCS augmented CBT did not predict improved homework compliance over the course of treatment, relative to the placebo augmented CBT group. However, when groups were collapsed, homework compliance was directly associated with treatment outcome. These findings suggest that while DCS may not increase homework compliance over time, more generally, homework compliance is an integral part of pediatric OCD treatment outcome.

Does d-Cycloserine Augmentation of CBT Improve Therapeutic Homework Compliance for Pediatric Obsessive–Compulsive Disorder?

PubMed Central

Park, Jennifer M.; Small, Brent J.; Geller, Daniel A.; Murphy, Tanya K.; Lewin, Adam B.; Storch, Eric A.

2014-01-01

Clinical studies in adults and children with obsessive–compulsive disorder (OCD) have shown that d-cycloserine (DCS) can improve treatment response by enhancing fear extinction learning during exposure-based psychotherapy. Some have hypothesized that improved treatment response is a function of increased compliance and engagement in therapeutic homework tasks, a core component of behavioral treatment. The present study examined the relationship between DCS augmented cognitive-behavioral therapy (CBT) and homework compliance in a double-blind, placebo controlled trial with 30 youth with OCD. All children received 10 CBT sessions, the last seven of which included exposure and response prevention paired with DCS or placebo dosed 1 h before the session started. Results suggested that DCS augmented CBT did not predict improved homework compliance over the course of treatment, relative to the placebo augmented CBT group. However, when groups were collapsed, homework compliance was directly associated with treatment outcome. These findings suggest that while DCS may not increase homework compliance over time, more generally, homework compliance is an integral part of pediatric OCD treatment outcome. PMID:24999301

Zoledronic acid modulates maturation of human monocyte-derived dendritic cells.

PubMed

Orsini, Giulia; Failli, Alessandra; Legitimo, Annalisa; Adinolfi, Barbara; Romanini, Antonella; Consolini, Rita

2011-12-01

Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. Besides its main bone antiresorptive activity, ZA displays antitumor properties, by triggering the expansion and activation of γδ T-cells, which exert an antitumor effect through dendritic cells (DCs). Several studies have reported the interaction between ZA and γδ T-cells, but the potential immunoregulatory activity of this drug on DCs has scarcely been investigated. Therefore, in this paper, we evaluated the effects of a therapeutic dose of ZA on the in vitro generation and maturation of DCs derived from peripheral blood monocytes of healthy adult donors. We demonstrate that ZA treatment did not affect DC differentiation, but inhibited DC maturation on lipopolysaccharide activation, as shown by the impaired expression of maturation surface markers and reduced ability to induce allogeneic T-cell proliferation. Interestingly, IL-10 secretion by mature DCs was significantly lower in ZA-treated cells than in controls. We conclude that ZA exerts its immunological in vitro activity also by modulating the maturation of DCs.

microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis.

PubMed

Busch, Martin; Zernecke, Alma

2012-08-01

Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T cell responses with a complex picture emerging, in which miRNAs cooperate or antagonize DC behavior, thereby promoting or counterbalancing inflammatory responses. As miRNAs regulate key functions of DCs known to control atherosclerotic vascular disease, their potential as a therapeutic target holds promise and should be attended to in future research.

Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells.

PubMed

Mascarell, Laurent; Lombardi, Vincent; Louise, Anne; Saint-Lu, Nathalie; Chabre, Henri; Moussu, Hélène; Betbeder, Didier; Balazuc, Anne-Marie; Van Overtvelt, Laurence; Moingeon, Philippe

2008-09-01

A detailed characterization of oral antigen-presenting cells is critical to improve second-generation sublingual allergy vaccines. To characterize oral dendritic cells (DCs) within lingual and buccal tissues from BALB/c mice with respect to their surface phenotype, distribution, and capacity to polarize CD4(+) T-cell responses. In situ analysis of oral DCs was performed by immunohistology. Purified DCs were tested in vitro for their capacity to capture, process, and present the ovalbumin antigen to naive CD4(+) T cells. In vivo priming of ovalbumin-specific T cells adoptively transferred to BALB/c mice was analyzed by cytofluorometry in cervical lymph nodes after sublingual administration of mucoadhesive ovalbumin. Three subsets of oral DCs with a distinct tissue distribution were identified: (1) a minor subset of CD207(+) Langerhans cells located in the mucosa itself, (2) a major subpopulation of CD11b(+)CD11c(-) and CD11b(+)CD11c(+) myeloid DCs at the mucosal/submucosal interface, and (3) B220(+)120G8(+) plasmacytoid DCs found in submucosal tissues. Purified myeloid and plasmacytoid oral DCs capture and process the antigen efficiently and are programmed to elicit IFN-gamma and/or IL-10 production together with a suppressive function in naive CD4(+) T cells. Targeting the ovalbumin antigen to oral DCs in vivo by using mucoadhesive particles establishes tolerance in the absence of cell depletion through the stimulation of IFN-gamma and IL-10-producing CD4(+) regulatory T cells in cervical lymph nodes. The oral immune system is composed of various subsets of tolerogenic DCs organized in a compartmentalized manner and programmed to induce T(H)1/regulatory T-cell responses.

WE-D-17A-01: A Dynamic Collimation System for Spot Scanned Proton Therapy: Conceptual Overview

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

Hyer, D; Hill, P; Wang, D

2014-06-15

Purpose: In the absence of a collimation system, the lateral penumbra in pencil beam scanning (PBS) proton therapy delivered at low energies is highly dependent on the spot size. This dependence, coupled with the fact that spot sizes increase with decreasing energy, reduces the benefit of the PBS technique for treating shallow tumors such as those found in the head and neck region. In order to overcome this limitation, a dynamic collimation system (DCS) was developed for sharpening the lateral penumbra of low energy proton therapy dose distributions delivered by PBS. Methods: The proposed DCS consists of two pairs ofmore » orthogonal trimmer blades which intercept the edges of the proton beam near the target edge in the beam's eye view. Each trimmer blade is capable of rapid motion in the direction perpendicular to the central beam axis by means of a linear motor, with maximum velocity and acceleration of 2.5 m/s and 19.6 m/s{sup 2}, respectively. Two-dimensional treatment plans were created both with and without the DCS for in-air spot sizes (σ-air) of 3, 5, 7, and 9 mm, representing a wide array of clinically available equipment. Results: In its current configuration, the snout of the DCS has outer dimensions of 22.6 × 22.6 cm{sup 2} and is capable of delivering a minimum treatment field size of 15 × 15 cm{sup 2}. Using off the shelf components, the constructed system would weigh less than 20 kg. The treatment plans created with the DCS yielded a reduction in the mean dose to normal tissue surrounding the target of 26.2–40.6% for spot sizes of 3–9 mm, respectively. Conclusion: The DCS can be integrated with current or future proton therapy equipment and we believe it will serve as a useful tool to further improve the next generation of proton therapy delivery.« less

Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state.

PubMed

Martens, Géraldine; Lejeune, Nicolas; O'Brien, Anthony Terrence; Fregni, Felipe; Martial, Charlotte; Wannez, Sarah; Laureys, Steven; Thibaut, Aurore

2018-05-02

Patients with chronic disorders of consciousness face a significant lack of treatment options. We aimed at investigating the feasibility and the behavioral effects of home-based transcranial direct current stimulation (tDCS), applied by relatives or caregivers, in chronic patients in minimally conscious state (MCS). Each participant received, in a randomized order, 20 sessions of active and 20 sessions of sham tDCS applied over the prefrontal cortex for 4 weeks; separated by 8 weeks of washout. Level of consciousness was assessed using the Coma Recovery Scale-Revised before the first stimulation (baseline), at the end of the 20 tDCS sessions (direct effects) and 8 weeks after the end of each stimulation period (long-term effects). Reported adverse events and data relative to the adherence (i.e., amount of sessions effectively received) were collected as well. Twenty-seven patients completed the study and 22 patients received at least 80% of the stimulation sessions. All patients tolerated tDCS well, no severe adverse events were noticed after real stimulation and the overall adherence (i.e., total duration of stimulation) was good. A moderate effect size (0.47 and 0.53, for modified intention to treat and per protocol analysis, respectively) was observed at the end of the 4 weeks of tDCS in favor of the active treatment. We demonstrated that home-based tDCS can be used adequately outside a research facility or hospital by patients' relatives or caregivers. In addition, 4 weeks of tDCS moderately improved the recovery of signs of consciousness in chronic MCS patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Enhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8(+) T cell-mediated cell death.

PubMed

Kim, Jin Hee; Kang, Tae Heung; Noh, Kyung Hee; Bae, Hyun Cheol; Kim, Seok-Ho; Yoo, Young Do; Seong, Seung-Yong; Kim, Tae Woo

2009-01-29

Dendritic cells (DCs) have become an important measure for the treatment of malignancies. Current DC preparations, however, generate short-lived DCs because they are subject to cell death from various apoptotic pressures. Antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) is one of the main obstacles to limit the DC-mediated immune priming since CTLs can recognize the target antigen expressing DCs as target cells and kill the DCs. CTLs secret perforin and serine protease granzymes during CTL killing. Perforin and serine protease granzymes induce the release of a number of mitochondrial pro-apoptotic factors, which are controlled by members of the BCL-2 family, such as BAK, BAX and BIM. FasL linking to Fas on DCs triggers the activation of caspase-8, which eventually leads to mitochondria-mediated apoptosis via truncation of BID. In this study, we tried to enhance the DC priming capacity by prolonging DC survival using anti-apoptotic siRNA targeting these key pro-apoptotic molecules in CTL killing. Human papillomavirus (HPV)-16 E7 antigen presenting DCs that were transfected with these anti-apoptotic siRNAs showed increased resistance to T cell-mediated death, leading to enhanced E7-specific CD8(+) T cell activation in vitro and in vivo. Among them, siRNA targeting BIM (siBIM) generated strongest E7-specific E7-specific CD8(+) T cell immunity. More importantly, vaccination with E7 presenting DCs transfected with siBIM was capable of generating a marked therapeutic effect in vaccinated mice. Our data indicate that ex vivo manipulation of DCs with siBIM may represent a plausible strategy for enhancing dendritic cell-based vaccine potency.

Dendritic cells infected by Ad-sh-SOCS1 enhance cytokine-induced killer (CIK) cell immunotherapeutic efficacy in cervical cancer models.

PubMed

Zheng, Yi; Hu, Bicheng; Xie, Shenggao; Chen, Xiaofan; Hu, Yuqian; Chen, Wanping; Li, Shanshan; Hu, Bo

2017-05-01

Cervical cancer constitutes a major problem in women's health worldwide, but the efficacy of the standard therapy is unsatisfactory. Cytokine-induced killer (CIK) cells exhibit antitumor activity against a variety of malignancies in preclinical models and have proven safe and effective in clinical trials. However, current CIK therapy has limitations and needs to be improved to meet the clinical requirements. The aim of this study was to investigate whether suppressing the expression of cytokine signaling 1 (SOCS1) in dendritic cells (DCs) can shorten in vitro CIK culture time and improve its antitumor efficacy. DCs were pre-cultured for 3 days before infected with adenovirus-mediated-SOCS1 short hairpin RNA (Ad-sh-SOCS1) and pulsed with CTL epitope peptides E7. The DCs infected by Ad-sh-SOCS1 (gmDCs) and CIKs were then co-cultured for 5 or 9 days, and CIK proliferation and antitumor activity were evaluated both in vitro and in vivo. Our data show that gmDCs significantly stimulated the expansion of co-cultured CIKs and increased the secretion of interferon-γ and interleukin-12. Moreover, gmDCs-activated CIKs showed higher cytotoxic activity against TC-1 cells expressing HPV16E6 and E7. Our in vivo study showed that the mice infused with gmDCs-activated CIKs on day 10 had an increased survival rate and prolonged survival time compared with the controls. Taken together, these results indicate that DCs modified by adenovirus-mediated SOCS1 silencing can promote CIKs expansion and enhance the efficacy of antitumor immunotherapy both in vitro and in vivo, which represents an effective therapeutic approach for cervical cancer and other tumors. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Anodal transcranial direct current stimulation enhances the effects of motor imagery training in a finger tapping task.

PubMed

Saimpont, Arnaud; Mercier, Catherine; Malouin, Francine; Guillot, Aymeric; Collet, Christian; Doyon, Julien; Jackson, Philip L

2016-01-01

Motor imagery (MI) training and anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex can independently improve hand motor function. The main objective of this double-blind, sham-controlled study was to examine whether anodal tDCS over the primary motor cortex could enhance the effects of MI training on the learning of a finger tapping sequence. Thirty-six right-handed young human adults were assigned to one of three groups: (i) who performed MI training combined with anodal tDCS applied over the primary motor cortex; (ii) who performed MI training combined with sham tDCS; and (iii) who received tDCS while reading a book. The MI training consisted of mentally rehearsing an eight-item complex finger sequence for 13 min. Before (Pre-test), immediately after (Post-test 1), and at 90 min after (Post-test 2) MI training, the participants physically repeated the sequence as fast and as accurately as possible. An anova showed that the number of sequences correctly performed significantly increased between Pre-test and Post-test 1 and remained stable at Post-test 2 in the three groups (P < 0.001). Furthermore, the percentage increase in performance between Pre-test and Post-test 1 and Post-test 2 was significantly greater in the group that performed MI training combined with anodal tDCS compared with the other two groups (P < 0.05). As a potential physiological explanation, the synaptic strength within the primary motor cortex could have been reinforced by the association of MI training and tDCS compared with MI training alone and tDCS alone. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Nrf2 suppresses the function of dendritic cells to facilitate the immune escape of glioma cells.

PubMed

Wang, Jialiang; Liu, Peng; Xin, Shaoyan; Wang, Zongbao; Li, Jun

2017-11-15

Nrf2 is presented in dendritic cells (DCs) and contributes to the maintenance of redox homeostasis. However, the expression pattern and function of Nrf2 in the maturation of DCs in the glioma-infiltrated microenvironment remain unrevealed. Our study aims to investigate the roles of Nrf2 in glioma cell-tamed DCs and their impact on the downstream T cell proliferation and cytotoxicity to glioma cells. It was showed that the inducible maturation of DCs was significantly suppressed after stimulation with tumor-conditioned medium (TCM) prepared from glioma cells (LN-18 and U118MG), as suggested by the decreased CD80, CD86 and IL-12 p70 expression and higher levels of IL-10 than the normal astrocyte medium treated DCs. Moreover, the TCM-exposed DCs had significantly increased expression and transcriptional activity of Nrf2 compared to the negative control. Nrf2 inhibition in DC cells substantially antagonized the inhibitory effects of TCM on the maturation and activation of DC cells, reflected by the elevated maturation markers and IL-12 p70. We further confirmed that Nrf2 inhibition in TCM-exposed DC cells promoted the proliferation of T cells as evaluated by the CFSE-labeled assay and Th1 response shown by the elevated production of IFN-γ. The cytotoxic T lymphocyte assay revealed that Nrf2 genetic suppression in DC cells greatly enhanced the capacity of T cells in the cytotoxicity to glioma cells dependent on the E:T ratio. Collectively, our study demonstrated that Nrf2 inhibition in DCs in glioma-exposed microenvironment could enhance the maturation of DCs and the subsequent activation of T cells and their cytotoxicity on glioma cells. Copyright © 2017. Published by Elsevier Inc.

ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) INCREASES ISOMETRIC STRENGTH OF SHOULDER ROTATORS MUSCLES IN HANDBALL PLAYERS.

PubMed

Hazime, Fuad Ahmad; da Cunha, Ronaldo Alves; Soliaman, Renato Rozenblit; Romancini, Ana Clara Bezerra; Pochini, Alberto de Castro; Ejnisman, Benno; Baptista, Abrahão Fontes

2017-06-01

Weakness of the rotator cuff muscles can lead to imbalances in the strength of shoulder external and internal rotators, change the biomechanics of the glenohumeral joint and predispose an athlete to injury. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has demonstrated promising results in a variety of health conditions. However few studies addressed its potential approach in the realm of athletics. The purpose of this study was to investigate if transcranial direct current stimulation (tDCS) technique increases the isometric muscle strength of shoulder external and internal rotators in handball athletes. Randomized, double-blind, placebo-controlled, crossover study. Eight female handball players aged between 17 and 21 years (Mean=19.65; SD=2.55) with 7.1 ± 4.8 years of experience in training, participating in regional and national competitions were recruited. Maximal voluntary isometric contraction (MVIC) of shoulder external and internal rotator muscles was evaluated during and after 30 and 60 minutes post one session of anodal and sham current (2mA; 0.057mA/cm 2 ) with a one-week interval between stimulations. Compared to baseline, MVIC of shoulder external and internal rotators significantly increased after real but not sham tDCS. Between-group differences were observed for external and internal rotator muscles. Maximal voluntary isometric contraction of external rotation increased significantly during tDCS, and 30 and 60 minutes post-tDCS for real tDCS compared to that for sham tDCS. For internal rotation MVIC increased significantly during and 60 minutes post-tDCS. The results indicate that transcranial direct current stimulation temporarily increases maximal isometric contractions of the internal and external rotators of the shoulder in handball players. 2.

Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age

PubMed Central

Heise, Kirstin-Friederike; Niehoff, Martina; Feldheim, J.-F.; Liuzzi, Gianpiero; Gerloff, Christian; Hummel, Friedhelm C.

2014-01-01

Changes in γ-aminobutyric acid (GABA) mediated synaptic transmission have been associated with age-related motor and cognitive functional decline. Since anodal transcranial direct current stimulation (atDCS) has been suggested to target cortical GABAergic inhibitory interneurons, its potential for the treatment of deficient inhibitory activity and functional decline is being increasingly discussed. Therefore, after-effects of a single session of atDCS on resting-state and event-related short-interval intracortical inhibition (SICI) as evaluated with double-pulse TMS and dexterous manual performance were examined using a sham-controlled cross-over design in a sample of older and younger participants. The atDCS effect on resting-state inhibition differed in direction, magnitude, and timing, i.e., late relative release of inhibition in the younger and early relative increase in inhibition in the older. More pronounced release of event-related inhibition after atDCS was exclusively seen in the older. Event-related modulation of inhibition prior to stimulation predicted the magnitude of atDCS-induced effects on resting-state inhibition. Specifically, older participants with high modulatory capacity showed a disinhibitory effect comparable to the younger. Beneficial effects on behavior were mainly seen in the older and in tasks requiring higher dexterity, no clear association with physiological changes was found. Differential effects of atDCS on SICI, discussed to reflect GABAergic inhibition at the level of the primary motor cortex, might be distinct in older and younger participants depending on the functional integrity of the underlying neural network. Older participants with preserved modulatory capacity, i.e., a physiologically “young” motor network, were more likely to show a disinhibitory effect of atDCS. These results favor individually tailored application of tDCS with respect to specific target groups. PMID:25071555

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials.

PubMed

Aparício, Luana V M; Guarienti, Fabiana; Razza, Lais Boralli; Carvalho, André F; Fregni, Felipe; Brunoni, André Russowsky

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies. To investigate the tolerability (rate of AEs) and acceptability (rate of dropouts) of tDCS. Systematic review and meta-analysis of tDCS randomized, sham-controlled trials in healthy or neuropsychiatric adult samples from the first date available to March 9, 2016. We only included parallel studies performing at least 5 tDCS sessions. An adapted version of CONSORT guidelines for reporting harms outcomes was used to evaluate AE reporting. Sixty-four studies (2262 participants) were included. They had a low risk of publication bias and methodological bias for the items assessed. Dropout rates in active and sham tDCS groups were, respectively, 6% and 7.2% (OR = 0.82 [0.59-1.14]). However, almost half of studies reported no dropouts and only 23.4% reported its reasons; when reported, the most frequent reasons were AEs and protocol violation. A tolerability meta-analysis was not performed, as most studies did not report AEs. The quality of AEs reporting was also limited, particularly in smaller studies and stroke studies. Although overall dropout rate was low and similar in active and sham groups, studies did not adequately describe AEs. An updated questionnaire and guidelines for assessment of AEs in tDCS trials are proposed in order to standardize the reporting of AE in the field. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcranial direct current stimulation improves isometric time to exhaustion of the knee extensors.

PubMed

Angius, L; Pageaux, B; Hopker, J; Marcora, S M; Mauger, A R

2016-12-17

Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. Nine subjects underwent a control (CON), placebo (SHAM) and two different tDCS montage sessions in a randomized design. In one tDCS session, the anodal electrode was placed over the left motor cortex and the cathodal on contralateral forehead (HEAD), while for the other montage the anodal electrode was placed over the left motor cortex and cathodal electrode above the shoulder (SHOULDER). tDCS was delivered for 10min at 2.0mA, after which participants performed an isometric time to exhaustion (TTE) test of the right knee extensors. Peripheral and central neuromuscular parameters were assessed at baseline, after tDCS application and after TTE. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle exercise-induced muscle pain (PAIN) were monitored during the TTE. TTE was longer and RPE lower in the SHOULDER condition (P<0.05). Central and peripheral parameters, and HR and PAIN did not present any differences between conditions after tDCS stimulation (P>0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A Distributed Control System Prototyping Environment to Support Control Room Modernization

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

Lew, Roger Thomas; Boring, Ronald Laurids; Ulrich, Thomas Anthony

Operators of critical processes, such as nuclear power production, must contend with highly complex systems, procedures, and regulations. Developing human-machine interfaces (HMIs) that better support operators is a high priority for ensuring the safe and reliable operation of critical processes. Human factors engineering (HFE) provides a rich and mature set of tools for evaluating the performance of HMIs, however the set of tools for developing and designing HMIs is still in its infancy. Here we propose a rapid prototyping approach for integrating proposed HMIs into their native environments before a design is finalized. This approach allows researchers and developers tomore » test design ideas and eliminate design flaws prior to fully developing the new system. We illustrate this approach with four prototype designs developed using Microsoft’s Windows Presentation Foundation (WPF). One example is integrated into a microworld environment to test the functionality of the design and identify the optimal level of automation for a new system in a nuclear power plant. The other three examples are integrated into a full-scale, glasstop digital simulator of a nuclear power plant. One example demonstrates the capabilities of next generation control concepts; another aims to expand the current state of the art; lastly, an HMI prototype was developed as a test platform for a new control system currently in development at U.S. nuclear power plants. WPF possesses several characteristics that make it well suited to HMI design. It provides a tremendous amount of flexibility, agility, robustness, and extensibility. Distributed control system (DCS) specific environments tend to focus on the safety and reliability requirements for real-world interfaces and consequently have less emphasis on providing functionality to support novel interaction paradigms. Because of WPF’s large user-base, Microsoft can provide an extremely mature tool. Within process control applications,WPF is platform independent and can communicate with popular full-scope process control simulator vendor plant models and DCS platforms.« less

The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

PubMed Central

Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

2015-01-01

Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

Effect of D-cycloserine in conjunction with fear extinction training on extracellular signal-regulated kinase activation in the medial prefrontal cortex and amygdala in rat.

PubMed

Gupta, Subhash C; Hillman, Brandon G; Prakash, Anand; Ugale, Rajesh R; Stairs, Dustin J; Dravid, Shashank M

2013-06-01

D-cycloserine (DCS) is currently under clinical trials for a number of neuropsychiatric conditions and has been found to augment fear extinction in rodents and exposure therapy in humans. However, the molecular mechanism of DCS action in these multiple modalities remains unclear. Here, we describe the effect of DCS administration, alone or in conjunction with extinction training, on neuronal activity (c-fos) and neuronal plasticity [phospho-extracellular signal-regulated kinase (pERK)] markers using immunohistochemistry. We found that intraperitoneal administration of DCS in untrained young rats (24-28 days old) increased c-fos- and pERK-stained neurons in both the prelimbic and infralimbic division of the medial prefrontal cortex (mPFC) and reduced pERK levels in the lateral nucleus of the central amygdala. Moreover, DCS administration significantly increased GluA1, GluN1, GluN2A, and GluN2B expression in the mPFC. In a separate set of animals, we found that DCS facilitated fear extinction and increased pERK levels in the infralimbic prefrontal cortex, prelimbic prefrontal cortex intercalated cells and lateral nucleus of the central amygdala, compared with saline control. In the synaptoneurosomal preparation, we found that extinction training increased iGluR protein expression in the mPFC, compared with context animals. No significant difference in protein expression was observed between extinction-saline and extinction-DCS groups in the mPFC. In contrast, in the amygdala DCS, the conjunction with extinction training led to an increase in iGluR subunit expression, compared with the extinction-saline group. Our data suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due to its ability to affect neuronal activity and signaling in the mPFC and amygdala subnuclei. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived Dendritic Cells and Increases Stimulation of T Cells.

PubMed

Silva-Cardoso, Sandra C; Affandi, Alsya J; Spel, Lotte; Cossu, Marta; van Roon, Joel A G; Boes, Marianne; Radstake, Timothy R D J

2017-07-01

Chemokines have been shown to play immune-modulatory functions unrelated to steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating CXCL4 are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role of dendritic cells (DCs) in immune activation, in this article we addressed the effect of CXCL4 on the phenotype and function of monocyte-derived DCs (moDCs). To this end, we compared innate and adaptive immune responses of moDCs with those that were differentiated in the presence of CXCL4. Already prior to TLR- or Ag-specific stimulation, CXCL4-moDCs displayed a more matured phenotype. We found that CXCL4 exposure can sensitize moDCs for TLR-ligand responsiveness, as illustrated by a dramatic upregulation of CD83, CD86, and MHC class I in response to TLR3 and TLR7/8-agonists. Also, we observed a markedly increased secretion of IL-12 and TNF-α by CXCL4-moDCs exclusively upon stimulation with polyinosinic-polycytidylic acid, R848, and CL075 ligands. Next, we analyzed the effect of CXCL4 in modulating DC-mediated T cell activation. CXCL4-moDCs strongly potentiated proliferation of autologous CD4 + T cells and CD8 + T cells and production of IFN-γ and IL-4, in an Ag-independent manner. Although the internalization of Ag was comparable to that of moDCs, Ag processing by CXCL4-moDCs was impaired. Yet, these cells were more potent at stimulating Ag-specific CD8 + T cell responses. Together our data support that increased levels of circulating CXCL4 may contribute to immune dysregulation through the modulation of DC differentiation. Copyright © 2017 by The American Association of Immunologists, Inc.

Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

PubMed

Kyriakareli, Artemis; Cousins, Sian; Pettorossi, Vito E; Bronstein, Adolfo M

2013-10-02

Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

Effects of vestibular rehabilitation combined with transcranial cerebellar direct current stimulation in patients with chronic dizziness: An exploratory study.

PubMed

Koganemaru, Satoko; Goto, Fumiyuki; Arai, Miki; Toshikuni, Keitaro; Hosoya, Makoto; Wakabayashi, Takeshi; Yamamoto, Nobuko; Minami, Shujiro; Ikeda, Satoshi; Ikoma, Katsunori; Mima, Tatsuya

Vestibular rehabilitation is useful to alleviate chronic dizziness in patients with vestibular dysfunction. It aims to induce neuronal plasticity in the central nervous system (especially in the cerebellum) to promote vestibular compensation. Transcranial cerebellar direct current stimulation (tcDCS) reportedly enhances cerebellar function. We investigated whether vestibular rehabilitation partially combined with tcDCS is superior to the use of rehabilitation alone for the alleviation of dizziness. Patients with chronic dizziness due to vestibular dysfunction received rehabilitation concurrently with either 20-min tcDCS or sham stimulation for 5 days. Pre- and post-intervention (at 1 month) dizziness handicap inventory (DHI) scores and psychometric and motor parameters were compared. Sixteen patients completed the study. DHI scores in the tcDCS group showed significant improvement over those in the sham group (Mann-Whitney U test, p = 0.033). Vestibular rehabilitation partially combined with tcDCS appears to be a promising approach. Copyright © 2017 Elsevier Inc. All rights reserved.

Prefrontal tDCS Decreases Pain in Patients with Multiple Sclerosis

PubMed Central

Ayache, Samar S.; Palm, Ulrich; Chalah, Moussa A.; Al-Ani, Tarik; Brignol, Arnaud; Abdellaoui, Mohamed; Dimitri, Dalia; Sorel, Marc; Créange, Alain; Lefaucheur, Jean-Pascal

2016-01-01

Background: In the last few years, transcranial direct current stimulation (tDCS) has emerged as an appealing therapeutic option to improve brain functions. Promising data support the role of prefrontal tDCS in augmenting cognitive performance and ameliorating several neuropsychiatric symptoms, namely pain, fatigue, mood disturbances, and attentional impairment. Such symptoms are commonly encountered in patients with multiple sclerosis (MS). Objective: The main objective of the current work was to evaluate the tDCS effects over the left dorsolateral prefrontal cortex (DLPFC) on pain in MS patients.Our secondary outcomes were to study its influence on attention, fatigue, and mood. Materials and Methods: Sixteen MS patients with chronic neuropathic pain were enrolled in a randomized, sham-controlled, and cross-over study.Patients randomly received two anodal tDCS blocks (active or sham), each consisting of three consecutive daily tDCS sessions, and held apart by 3 weeks. Evaluations took place before and after each block. To evaluate pain, we used the Brief Pain Inventory (BPI) and the Visual Analog Scale (VAS). Attention was assessed using neurophysiological parameters and the Attention Network Test (ANT). Changes in mood and fatigue were measured using various scales. Results: Compared to sham, active tDCS yielded significant analgesic effects according to VAS and BPI global scales.There were no effects of any block on mood, fatigue, or attention. Conclusion: Based on our results, anodal tDCS over the left DLPFC appears to act in a selective manner and would ameliorate specific symptoms, particularly neuropathic pain. Analgesia might have occurred through the modulation of the emotional pain network. Attention, mood, and fatigue were not improved in this work. This could be partly attributed to the short protocol duration, the small sample size, and the heterogeneity of our MS cohort. Future large-scale studies can benefit from comparing the tDCS effects over different cortical sites, changing the stimulation montage, prolonging the duration of protocol, and coupling tDCS with neuroimaging techniques for a better understanding of its possible mechanism of action. PMID:27092048

Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T cell – Th17 Balance

PubMed Central

George, Mariam Mathew; Vignesh, Kavitha Subramanian; Landero Figueroa, Julio A.; Caruso, Joseph A.; Deepe, George S.

2016-01-01

Zn is an essential metal for development and maintenance of both the innate and adaptive compartments of the immune system. Zn homeostasis impacts maturation of dendritic cells (DCs) that are important in shaping T cell responses. The mechanism by which Zn regulates the tolerogenic phenotype of DCs remains largely unknown. In this study, we investigated the effect of Zn on DC phenotype and the generation of forkhead box P3 (FoxP3+) regulatory T cells (Tregs) using a model of Histoplasma capsulatum fungal infection. Exposure of bone marrow derived DCs to Zn in vitro induced a tolerogenic phenotype by diminishing surface major histocompatibility complex (MHC)II and promoting the tolerogenic markers, programmed death-ligand (PD-L)1, PD-L2 and the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO). Zn triggered tryptophan degradation by IDO and kynurenine production by DCs and strongly suppressed the proinflammatory response to stimulation by toll like receptor (TLR) ligands. In vivo, Zn supplementation and subsequent H. capsulatum infection supressed MHCII on DCs, enhanced PD-L1 and PD-L2 expression on MHCIIlo DCs and skewed the Treg - Th17 balance in favour of FoxP3+ Tregs while decreasing Th17 cells. Thus, Zn shapes the tolerogenic potential of DCs in vitro and in vivo and promotes Tregs during fungal infection. PMID:27465530

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

PubMed

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.

HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells

PubMed Central

Gougeon, M-L; Melki, M-T; Saïdi, H

2012-01-01

Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense. It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells. The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK–DC synapse. HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells. This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis. PMID:22033335

Effective Targeted Gene Delivery to Dendritic Cells via Synergetic Interaction of Mannosylated Lipid with DOPE and BCAT

PubMed Central

Kim, Hee-Kwon; Wei, Huiling; Kulkarni, Aditya; Pogranichniy, Roman M.; Thompson, David H.

2012-01-01

The efficient delivery of plasmids encoding antigenic determinants into dendritic cells (DCs) that control immune response is a promising strategy for rapid development of new vaccines. In this study, we prepared a series of targeted cationic lipoplex based on two synthetic lipid components, mannose-poly(ethylene glycol, MW3000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (Mannose-PEG3000-DSPE) and O-(2R-1,2-di-O-(1'Z,9'Z-octadecadienyl)-glycerol)-3-N-(bis-2-aminoethyl)-carbamate (BCAT), that were formulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for evaluation as non-viral vectors for transgene expression in DCs. First, we optimized the N:P ratio for maximum transfection and then screened the effects of mannose targeting for further enhancement of transfection levels. Our results indicate that efficient delivery of gWIZ GFP plasmid into DCs was observed for mannose compositions of ~10%, whereas low transfection efficiencies were observed with non-targeted formulations. Mannose-targeted lipofectamine complexes also showed high GFP expression levels in DCs relative to non-targeted lipofectamine controls. The best transfection performance was observed using 10 mol % Mannose-PEG3000-DSPE, 60 mol% BCAT, and 30 mol % DOPE, indicating that the most efficient delivery into DCs occurs via synergistic interaction between mannose targeting and acid-labile, fusogenic BCAT:DOPE formulations. Our data suggest that mannose-PEG3000-DSPE:BCAT:DOPE formulations may be effective gene delivery vehicles for the development of DC-based vaccines. PMID:22229467

D-cycloserine enhances generalization of fear extinction in children.

PubMed

Byrne, Simon P; Rapee, Ronald M; Richardson, Rick; Malhi, Gin S; Jones, Michael; Hudson, Jennifer L

2015-06-01

For exposure therapy to be successful, it is essential that fear extinction learning extends beyond the treatment setting. D-cycloserine (DCS) may facilitate treatment gains by increasing generalization of extinction learning, however, its effects have not been tested in children. We examined whether DCS enhanced generalization of fear extinction learning across different stimuli and contexts among children with specific phobias. The study was a double-blind placebo-controlled randomized controlled trial among dog or spider phobic children aged 6-14. Participants ingested either 50 mg of DCS (n = 18) or placebo (n = 17) before receiving a single prolonged exposure session to their feared stimulus. Return of fear was examined 1 week later to a different stimulus (a different dog or spider), presented in both the original treatment context and an alternate context. Avoidance and fear were measured with Behavior Approach Tests (BATs), where the child was asked to increase proximity to the stimulus while reporting their fear level. There were no differences in BAT performance between groups during the exposure session or when a new stimulus was later presented in the treatment context. However, when the new stimulus was presented in a different context, relative to placebo, the DCS group showed less avoidance (P = .03) and less increase in fear (P = .04) with moderate effect sizes. DCS enabled children to better retain their fear extinction learning. This new learning generalized to different stimuli and contexts. © 2015 Wiley Periodicals, Inc.

Sensorimotor Rhythm BCI with Simultaneous High Definition-Transcranial Direct Current Stimulation Alters Task Performance.

PubMed

Baxter, Bryan S; Edelman, Bradley J; Nesbitt, Nicholas; He, Bin

Transcranial direct current stimulation (tDCS) has been used to alter the excitability of neurons within the cerebral cortex. Improvements in motor learning have been found in multiple studies when tDCS was applied to the motor cortex before or during task learning. The motor cortex is also active during the performance of motor imagination, a cognitive task during which a person imagines, but does not execute, a movement. Motor imagery can be used with noninvasive brain computer interfaces (BCIs) to control virtual objects in up to three dimensions, but to master control of such devices requires long training times. To evaluate the effect of high-definition tDCS on the performance and underlying electrophysiology of motor imagery based BCI. We utilize high-definition tDCS to investigate the effect of stimulation on motor imagery-based BCI performance across and within sessions over multiple training days. We report a decreased time-to-hit with anodal stimulation both within and across sessions. We also found differing electrophysiological changes of the stimulated sensorimotor cortex during online BCI task performance for left vs. right trials. Cathodal stimulation led to a decrease in alpha and beta band power during task performance compared to sham stimulation for right hand imagination trials. These results suggest that unilateral tDCS over the sensorimotor motor cortex differentially affects cortical areas based on task specific neural activation. Copyright © 2016 Elsevier Inc. All rights reserved.

Realization of BP neural network modeling based on NOXof CFB boiler in DCS

NASA Astrophysics Data System (ADS)

Bai, Jianyun; Zhu, Zhujun; Wang, Qi; Ying, Jiang

2018-02-01

In the CFB boiler installed with SNCR denitrification system, the mass concentration of NO X is difficult to be predicted by the conventional mathematical model, and the step response mathematical model, obtained by using the step disturbance test of ammonia injection,is inaccurate. this paper presents two kinds of BP neural network model, according to the relationship between the generated mass concentration of NO X and the load, the ratio of air to coal without using the SNCR system, as well as the relationship between the tested mass concentration of NO X and the load, the ratio of air to coal and the amount of ammonia using the SNCR system. then itrealized the on-line prediction of the mass concentration of NO X and the remaining mass concentration of NO X after reductionreaction in DCS system. the practical results show that the average error per hour between generation and the prediction of the amount of NO X mass concentration is within 10 mg/Nm3,the reducing reaction of measured and predicted hourly average error is within 2 mg/Nm3, all in error range, which provides a more accurate model for solvingthe problem on NO X automatic control of SNCR system.

Preliminary study of efficacy of dynamic compression system in the correction of typical pectus carinatum.

PubMed

Lopez, Manuel; Patoir, Arnaud; Varlet, François; Perez-Etchepare, Eduardo; Tiffet, Théophile; Villard, Aurelien; Tiffet, Olivier

2013-11-01

This preliminary study evaluates, by qualitative score, the efficacy of the dynamic compression system (DCS) with a pressure-measuring device in the treatment of pectus carinatum (PC) as an alternative to surgery. A total of 68 patients (infants, adolescents and young adults) presenting with typical PC (64 males and 4 females) were evaluated in our Chest Wall Deformities Unit, between October 2011 and February 2013. The criteria for including subjects were: patients with typical condrogladiolar PC and pressure for initial correction (PIC) ≤ 9 PSI (pound square inch). Seven patients were excluded in this study: three typical PC were treated by minimal invasive surgery (Abramson technique) due to highly elevated PIC and four atypical PC, hybrids forms (PE and PC) were treated by cup suction for pectus excavatum and by the DCS for the PC. The management protocol included: adjustment of the DCS, strengthening exercises and monthly clinical follow-up. The partial and final results were evaluated by the patients, by their parents or by both, using a qualitative scoring scale that was measured in a three-step grading system, where C is a low or very low result, B is acceptable and A is a very good or excellent result. A total of 61 patients (59 males and 2 females) presenting with typical PC were treated by the DCS and included: symmetric PC in 43 cases and asymmetric PC in 18 cases. The mean age was 13.5 years (5-25). The mean PIC was 6.3 PSI (3-9 PSI). The mean utilization time was 19 h daily. The patients were divided into three groups. In Group I, consisting of 35 cases, all the patients have already completed the treatment with excellent aesthetic results (A). In 12 cases, Group II, the normal shape of the thorax has been obtained; all the patients in this group rated their results as excellent (A); however, these patients are still wearing the brace as a retainer for 3 additional months. Fourteen patients, Group III, are progressing and improving under active treatment, and surgeons and patients are very satisfied with the initial results. None of the 61 patients in this study abandoned the treatment and no complications were found. This preliminary study demonstrated that the DCS with a pressure-measuring device is a minimal invasive system effective for treatment of PC in patients where the anterior chest wall is still compliant. The control of different pressure measurements could be used as the inclusion criterion as well as a predictive factor for aesthetic results and treatment duration.

TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets

PubMed Central

Han, Sun Murray; Na, Hye Young; Ham, Onju; Choi, Wanho; Sohn, Moah; Ryu, Seul Hye; In, Hyunju; Hwang, Ki-Chul

2016-01-01

Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s). PMID:26937233

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

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

Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation ofmore » recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.« less

Motor cortex guides selection of predictable movement targets

PubMed Central

Woodgate, Philip J.W.; Strauss, Soeren; Sami, Saber A.; Heinke, Dietmar

2016-01-01

The present paper asks whether the motor cortex contributes to prediction-based guidance of target selection. This question was inspired by recent evidence that suggests (i) recurrent connections from the motor system into the attentional system may extract movement-relevant perceptual information and (ii) that the motor cortex cannot only generate predictions of the sensory consequences of movements but may also operate as predictor of perceptual events in general. To test this idea we employed a choice reaching task requiring participants to rapidly reach and touch a predictable or unpredictable colour target. Motor cortex activity was modulated via transcranial direct current stimulation (tDCS). In Experiment 1 target colour repetitions were predictable. Under such conditions anodal tDCS facilitated selection versus sham and cathodal tDCS. This improvement was apparent for trajectory curvature but not movement initiation. Conversely, where no predictability of colour was embedded reach performance was unaffected by tDCS. Finally, the results of a key-press experiment suggested that motor cortex involvement is restricted to tasks where the predictable target colour is movement-relevant. The outcomes are interpreted as evidence that the motor system contributes to the top-down guidance of selective attention to movement targets. PMID:25835319

Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus.

PubMed

Cole, Suzanne; Walsh, Alice; Yin, Xuefeng; Wechalekar, Mihir D; Smith, Malcolm D; Proudman, Susanna M; Veale, Douglas J; Fearon, Ursula; Pitzalis, Costantino; Humby, Frances; Bombardieri, Michele; Axel, Amy; Adams, Homer; Chiu, Christopher; Sharp, Michael; Alvarez, John; Anderson, Ian; Madakamutil, Loui; Nagpal, Sunil; Guo, Yanxia

2018-05-02

Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target. We demonstrated that the plasma cell/plasmablast-related genes CD38, XBP1, IRF4, PRDM1, IGJ and TNFSF13B are significantly up-regulated in synovial biopsies from patients with arthralgia, undifferentiated arthritis (UA), early RA and established RA as compared to healthy controls and control patients with osteoarthritis. In addition, the highest CD38 expression was observed on plasma cells and plasmablasts compared to natural killer (NK) cells, classical dendritic cells (DCs), plasmacytoid DCs (pDCs) and T cells, in blood from healthy controls and patients with SLE and RA. Furthermore, IHC showed CD38 staining in the same region as CD3 and CD138 staining in synovial tissue biopsies from patients with early RA. Most importantly, our data show for the first time that daratumumab effectively depletes plasma cells/plasmablasts in PBMC from patients with SLE and RA in a dose-dependent manner ex vivo. These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinically for the treatment of both RA and SLE.

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data.

PubMed

Mataix-Cols, David; Fernández de la Cruz, Lorena; Monzani, Benedetta; Rosenfield, David; Andersson, Erik; Pérez-Vigil, Ana; Frumento, Paolo; de Kleine, Rianne A; Difede, JoAnn; Dunlop, Boadie W; Farrell, Lara J; Geller, Daniel; Gerardi, Maryrose; Guastella, Adam J; Hofmann, Stefan G; Hendriks, Gert-Jan; Kushner, Matt G; Lee, Francis S; Lenze, Eric J; Levinson, Cheri A; McConnell, Harry; Otto, Michael W; Plag, Jens; Pollack, Mark H; Ressler, Kerry J; Rodebaugh, Thomas L; Rothbaum, Barbara O; Scheeringa, Michael S; Siewert-Siegmund, Anja; Smits, Jasper A J; Storch, Eric A; Ströhle, Andreas; Tart, Candyce D; Tolin, David F; van Minnen, Agnes; Waters, Allison M; Weems, Carl F; Wilhelm, Sabine; Wyka, Katarzyna; Davis, Michael; Rück, Christian; Altemus, Margaret; Anderson, Page; Cukor, Judith; Finck, Claudia; Geffken, Gary R; Golfels, Fabian; Goodman, Wayne K; Gutner, Cassidy; Heyman, Isobel; Jovanovic, Tanja; Lewin, Adam B; McNamara, Joseph P; Murphy, Tanya K; Norrholm, Seth; Thuras, Paul

2017-05-01

Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.