Is Motor Learning Mediated by tDCS Intensity?

OpenAIRE

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

2013-01-01

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

ATLAS DAQ/HLT rack DCS

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Science.gov (United States)

Fricova, Jitka; Englerova, Katerina; Rokyta, Richard

2016-10-01

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

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

Science.gov (United States)

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

2018-06-01

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

Project managing your simulator DCS upgrade

International Nuclear Information System (INIS)

Carr, S.

2006-01-01

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

Technical Support for the development of DCS

International Nuclear Information System (INIS)

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

2008-05-01

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

DCS emulator development for the ACR-1000 simulator

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Science.gov (United States)

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.

Technical Support for the development of DCS

Energy Technology Data Exchange (ETDEWEB)

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

2008-05-15

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

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-01-08

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

TileDCS web system

International Nuclear Information System (INIS)

Maidantchik, C; Ferreira, F; Grael, F

2010-01-01

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

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

Science.gov (United States)

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

2016-10-15

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

Westwood, Samuel J; Romani, Cristina

2017-09-01

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2017-09-01

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

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

Science.gov (United States)

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

2017-01-05

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

DCS Budget Tracking System

Data.gov (United States)

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

Hits and Misses: Leveraging tDCS to Advance Cognitive Research

Directory of Open Access Journals (Sweden)

Marian E Berryhill

2014-07-01

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

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

Directory of Open Access Journals (Sweden)

Doreen Krumbiegel

2005-01-01

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

TileCal TDAQ/DCS communication

CERN Document Server

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

2007-01-01

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

Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.

Directory of Open Access Journals (Sweden)

Qinghong Wang

Full Text Available IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg efficiently induces IL-23 secretion in a mannose receptor (MR-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4(+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.

Longitudinal tDCS: Consistency across Working Memory Training Studies

Directory of Open Access Journals (Sweden)

Marian E. Berryhill

2017-04-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Science.gov (United States)

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

2014-06-01

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

Communication between Trigger/DAQ and DCS in ATLAS

International Nuclear Information System (INIS)

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

2001-01-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

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

The ATLAS Tile Calorimeter DCS for Run 2

CERN Document Server

Pedro Martins, Filipe Manuel; The ATLAS collaboration

2016-01-01

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

The ATLAS Tile Calorimeter DCS for Run 2

CERN Document Server

Pedro Martins, Filipe Manuel; The ATLAS collaboration

2016-01-01

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

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

Science.gov (United States)

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

2017-01-01

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

ATLAS Muon DCS Upgrades and Optimizations

CERN Document Server

Bakalis, Christos; The ATLAS collaboration

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

Anirban eDutta

2015-08-01

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

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

Science.gov (United States)

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

2016-03-01

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

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

Science.gov (United States)

Jog, Mayank Anant

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

Evaluation for nuclear safety-critical software reliability of DCS

International Nuclear Information System (INIS)

Liu Ying

2015-01-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

Directory of Open Access Journals (Sweden)

Hui-Zhong Wen

2017-06-01

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

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

Science.gov (United States)

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

2016-10-01

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

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

Science.gov (United States)

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.

Fermented Citrus Lemon Reduces Liver Injury Induced by Carbon Tetrachloride in Rats

Directory of Open Access Journals (Sweden)

Yi Jinn Lillian Chen

2018-01-01

Full Text Available Fermented lemon juice displays a variety of important biological activities, including anti-inflammatory and antioxidant capabilities. The aim of the present study is to investigate hepatic-protective effects of no-sugar-added fermented lemon juice (FLJ for liver inflammation caused by carbon tetrachloride (CCl4 in rats. Rats are divided into six groups: H2O, CCl4 + H2O, CCl4 + silymarin, and CCl4 plus three different FLJ doses by oral administration, respectively. The results show that the contents of plasma ALT and AST, hepatic lipid peroxidation, splenomegaly, and liver water are reduced significantly in rats under FLJ treatment, and pathological examination of liver fibrosis is improved. The reduced hepatic injury by increasing liver soluble protein and glutathione and albumin is observed in FLJ treated groups, and FLJ has comparable efficacies to medicine silymarin in liver therapies. The no-sugar-added FLJ differs from traditional fermentation by adding lots of sugar and prevents any hidden sugar intake while taking it as a complimentary treatment for liver inflammation. The green color and the taste of sourness are both associated with treating and healing the liver based on the five-element theory in traditional Chinese medicine, and the green and sour FLJ may be applied to the ancient theory in preventing hepatic injury accordingly.

Induction and maintenance of protective CD8+ T cells against malaria liver stages: implications for vaccine development

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Sze-Wah Tse

2011-08-01

Full Text Available CD8+ T cells against malaria liver stages represent a major protective immune mechanism against infection. Following induction in the peripheral lymph nodes by dendritic cells (DCs, these CD8+ T cells migrate to the liver and eliminate parasite infected hepatocytes. The processing and presentation of sporozoite antigen requires TAP mediated transport of major histocompatibility complex class I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also dependent on endosome-mediated cross presentation while this mechanism is not required for epitope presentation on hepatocytes. Protective CD8+ T cell responses are strongly dependent on the presence of CD4+ T cells and the capacity of sporozoite antigen to persist for a prolonged period of time. While human trials with subunit vaccines capable of inducing antibodies and CD4+ T cell responses have yielded encouraging results, an effective anti-malaria vaccine will likely require vaccine constructs designed to induce protective CD8+ T cells against malaria liver stages.

Understanding public (misunderstanding of tDCS for enhancement

Directory of Open Access Journals (Sweden)

Laura Yenisa Cabrera

2015-04-01

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

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

Directory of Open Access Journals (Sweden)

Anne eSauvaget

2015-10-01

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

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

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Alexa Riggs

2018-05-01

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

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

Science.gov (United States)

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

2018-01-01

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

Delayed plastic responses to anodal tDCS in older adults

Directory of Open Access Journals (Sweden)

Hakuei eFujiyama

2014-06-01

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

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

Science.gov (United States)

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

2017-01-08

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

Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines.

Science.gov (United States)

Zong, L; Yu, Q H; Du, Y X; Deng, X M

2014-02-01

Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

Energy Technology Data Exchange (ETDEWEB)

Zong, L. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China); No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Yu, Q. H. [Second Military Medical University, Changhai Hospital, Department of Gastroenterology, Shanghai, China, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai (China); Du, Y. X. [No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Deng, X. M. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China)

2014-03-03

Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

International Nuclear Information System (INIS)

Zong, L.; Yu, Q.H.; Du, Y.X.; Deng, X.M.

2014-01-01

Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis

Configuration-defined control algorithms with the ASDEX Upgrade DCS

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-15

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

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

Science.gov (United States)

Bennabi, Djamila; Haffen, Emmanuel

2018-01-01

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

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

Science.gov (United States)

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.

New cooling regulation technology of secondary cooling station in DCS

Energy Technology Data Exchange (ETDEWEB)

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

2008-07-01

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

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

Science.gov (United States)

Lefebvre, Stephanie; Liew, Sook-Lei

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-12-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

Directory of Open Access Journals (Sweden)

L. Zong

2014-03-01

Full Text Available Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN and lipopolysaccharide (LPS in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST and alanine aminotransferase (ALT. Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

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

Science.gov (United States)

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

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Kyrana Tsapkini

2015-05-01

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

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

Science.gov (United States)

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

2018-01-01

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

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

Science.gov (United States)

Pixa, Nils H; Pollok, Bettina

2018-01-01

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

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

Science.gov (United States)

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

2016-07-18

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.

Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

Science.gov (United States)

Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

2018-05-01

The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

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

Science.gov (United States)

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

2016-06-01

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

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

Science.gov (United States)

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

2018-02-01

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

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

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Anna-Katharine eBrem

2014-09-01

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

The Integration of DCS I/O to an Existing PLC

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Sadhukhan, Debashis; Mihevic, John

2013-01-01

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

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

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Miguel eAlonso-Alonso

2013-08-01

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

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

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

2016-08-02

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

Functional connectivity substrates for tDCS response in Minimally Conscious State patients

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Carlo Cavaliere

2016-11-01

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

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

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

2017-01-01

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

Anodal tDCS to V1 blocks visual perceptual learning consolidation.

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

2013-06-01

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

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

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

2017-01-01

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

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

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

2011-01-01

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

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

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

2017-09-01

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

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

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

2013-03-14

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

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

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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.

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

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

2015-08-15

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

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

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Justin Nelson

2016-11-01

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

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

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

2016-01-01

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

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

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Jamart Jacques

2010-03-01

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

DCS cabinet power loss analysis for CPR1000 nuclear power plant

International Nuclear Information System (INIS)

Zhou Liang; Zhao Yanfeng; Sun Yongbin

2014-01-01

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

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

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

2017-10-11

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

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

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

2016-01-01

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

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

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

2017-08-01

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

Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice.

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Sanches, Sheila Cristina; Ramalho, Leandra Naira Z; Mendes-Braz, Mariana; Terra, Vânia Aparecida; Cecchini, Rubens; Augusto, Marlei Josiele; Ramalho, Fernando Silva

2014-05-01

Riboflavin has been shown to exhibit anti-inflammatory and antioxidant properties in the settings of experimental sepsis and ischaemia/reperfusion (I/R) injury. We investigated the effect of riboflavin on normothermic liver I/R injury. Mice were submitted to 60 min of ischaemia plus saline or riboflavin treatment (30 μmoles/kg BW) followed by 6 h of reperfusion. Hepatocellular injury was evaluated by aminotransferase levels, reduced glutathione (GSH) content and the histological damage score. Hepatic neutrophil accumulation was assessed using the naphthol method and by measuring myeloperoxidase activity. Hepatic oxidative/nitrosative stress was estimated by immunohistochemistry. Liver endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) amounts were assessed by immunoblotting and a chemiluminescence assay. Riboflavin significantly reduced serum and histological parameters of hepatocellular damage, neutrophil infiltration and oxidative/nitrosative stress. Furthermore, riboflavin infusion partially recovered hepatic GSH reserves and decreased the liver contents of eNOS/iNOS and NO. These data indicate that riboflavin exerts antioxidant and anti-inflammatory effects in the ischaemic liver, protecting hepatocytes against I/R injury. The mechanism of these effects appears to be related to the intrinsic antioxidant potential of riboflavin/dihydroriboflavin and to reduced hepatic expression of eNOS/iNOS and reduced NO levels, culminating in attenuation of oxidative/nitrosative stress and the acute inflammatory response. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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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.

Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

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Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

2016-07-01

Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

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

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

2015-01-01

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

Reducing transfusion requirements in liver transplantation.

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Donohue, Ciara I; Mallett, Susan V

2015-12-24

Liver transplantation (LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusion-free transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical "piggyback" techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management (PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT.

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

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Brenton Hordacre

2018-06-01

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

Mangosteen peel extract reduces formalin-induced liver cell death in rats

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Afiana Rohmani

2014-08-01

Full Text Available Background Formalin is a xenobiotic that is now commonly used as a preservative in the food industry. The liver is an organ that has the highest metabolic capacity as compared to other organs. Mangosteen or Garcinia mangostana Linn (GML peel contains xanthones, which are a source of natural antioxidants. The purpose of this study was to evaluate the effect of mangosteen peel extract on formalin-induced liver cell mortality rate and p53 protein expression in Wistar rats. Methods Eighteen rats received formalin orally for 2 weeks, and were subsequently divided into 3 groups, consisting of the formalin-control group receiving a placebo and treatment groups 1 and 2, which were treated with mangosteen peel extract at doses of 200 and 400 mg/kgBW/day, respectively. The treatment was carried out for 1 week, and finally the rats were terminated. The differences in liver cell mortality rate and p53 protein expression were analyzed. Results One-way ANOVA analysis showed significant differences in liver cell mortality rate among the three groups (p=0.004. The liver cell mortality rate in the treatment group receiving 400 mg/kgBW/day extract was lower than that in the formalin-control group. There was no p53 expression in all groups. Conclusions Garcinia mangostana Linn peel extract reduced the mortality rate of liver cells in rats receiving oral formalin. Involvement of p53 expression in liver cell mortality in rats exposed to oral formalin is presumably negligible.

JACoW ADAPOS: An architecture for publishing ALICE DCS conditions data

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

2018-01-01

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

The Immunomodulatory Potential of tolDCs Loaded with Heat Shock Proteins

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Willem van Eden

2017-11-01

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

Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers

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van Rijn, Rianne; van Leeuwen, Otto B.; Matton, Alix P. M.; Burlage, Laura C.; Wiersema‐Buist, Janneke; van den Heuvel, Marius C.; de Kleine, Ruben H. J.; de Boer, Marieke T.; Gouw, Annette S. H.

2018-01-01

Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been advocated as a method to reduce ischemia/reperfusion injury (IRI). This study aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death (DCD) liver transplantation. In a recently performed phase 1 trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS; http://www.trialregister.nl NTR4493). Bile duct biopsies were obtained at the end of SCS (before DHOPE; baseline) and after graft reperfusion in the recipient. Histological severity of biliary injury was graded according to an established semiquantitative grading system. Twenty liver transplantations using DCD livers not preserved with DHOPE served as controls. Baseline characteristics and the degree of bile duct injury at baseline (end of SCS) were similar between both groups. In controls, the degree of stroma necrosis (P = 0.002) and injury of the deep peribiliary glands (PBG; P = 0.02) increased after reperfusion compared with baseline. In contrast, in DHOPE‐preserved livers, the degree of bile duct injury did not increase after reperfusion. Moreover, there was less injury of deep PBG (P = 0.04) after reperfusion in the DHOPE group compared with controls. In conclusion, this study suggests that DHOPE reduces IRI of bile ducts after DCD liver transplantation. Liver Transplantation 24 655–664 2018 AASLD. PMID:29369470

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

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Shaowei Zhan

2018-03-01

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

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS

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Natalie Dittert

2018-04-01

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

Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition

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

2015-01-01

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

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

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

2013-01-01

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

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

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Jonna eNilsson

2015-12-01

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

GSK-3β Inhibition Attenuates CLP-Induced Liver Injury by Reducing Inflammation and Hepatic Cell Apoptosis

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Hui Zhang

2014-01-01

Full Text Available Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK- 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP, and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB but enhanced the transcriptional activity of cAMP response element binding protein (CREB in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.

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

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Leigh E Charvet

2015-03-01

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

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

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

2013-01-01

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

Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis.

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Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana

2016-01-01

hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.

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

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Marie-Anne Vanderhasselt

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

tDCS stimulation segregates words in the brain: evidence from aphasia

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Valentina eFiori

2013-06-01

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

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

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

2016-01-01

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

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

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

2017-01-01

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

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

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

2017-03-01

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

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

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Xiaoming Zhang

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

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

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

2014-05-07

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

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

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

2016-01-30

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

Comprehensive evaluation method in application of nuclear DCS product design

International Nuclear Information System (INIS)

Wang Weixin; Zhao Zhemin; Shi Yingbin

2014-01-01

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

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

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

2017-01-01

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

Impaired liver regeneration is associated with reduced cyclin B1 in natural killer T cell-deficient mice.

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Ben Ya'acov, Ami; Meir, Hadar; Zolotaryova, Lydia; Ilan, Yaron; Shteyer, Eyal

2017-03-23

It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice. Ki-67 and proliferating cell nuclear antigen were used to measure hepatocytes proliferation. Expression of hepatic cyclin B1 and proliferating cell nuclear antigen were evaluated by Western Blot and liver injury was assessed by ALT and histology. Natural killer T cells- deficient or mice injected with anti CD1d antibodies exhibited reduced liver regeneration. These mice were considerably resistant to ConA-induced liver injury. In the absence of NKT cells hepatic proliferating cell nuclear antigen and cyclin B1 decreased in mice injected with Concanvalin A before partial hepatectomy. This was accompanied with reduced serum interleukin-6 levels. Natural killer T cells play an important role in liver regeneration, which is associated with cyclin B1 and interleukin-6.

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

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

2016-10-01

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

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

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Anna Lisa Mangia

2014-08-01

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

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

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Pergolizzi, Denise; Chua, Elizabeth F.

2016-01-01

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

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

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

2016-10-01

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

DCS-Neural-Network Program for Aircraft Control and Testing

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Jorgensen, Charles C.

2006-01-01

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

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

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Pripfl, Jürgen; Lamm, Claus

2015-02-01

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

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

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Hayley Thair

2017-11-01

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

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

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

2017-01-01

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

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

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

2017-02-01

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

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

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

2017-01-01

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

New Concept For Alarm Structure And Management In Dcs Systems

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Mohammed Hegazy

2015-08-01

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

A reliability evaluation method for NPP safety DCS application software

International Nuclear Information System (INIS)

Li Yunjian; Zhang Lei; Liu Yuan

2014-01-01

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

Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model.

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López-Soldado, Iliana; Zafra, Delia; Duran, Jordi; Adrover, Anna; Calbó, Joaquim; Guinovart, Joan J

2015-03-01

We generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTG(OE)), which results in an increase in liver glycogen. When fed a high-fat diet (HFD), these animals reduced their food intake. The resulting effect was a lower body weight, decreased fat mass, and reduced leptin levels. Furthermore, PTG overexpression reversed the glucose intolerance and hyperinsulinemia caused by the HFD and protected against HFD-induced hepatic steatosis. Of note, when fed an HFD, PTG(OE) mice did not show the decrease in hepatic ATP content observed in control animals and had lower expression of neuropeptide Y and higher expression of proopiomelanocortin in the hypothalamus. Additionally, after an overnight fast, PTG(OE) animals presented high liver glycogen content, lower liver triacylglycerol content, and lower serum concentrations of fatty acids and β-hydroxybutyrate than control mice, regardless of whether they were fed an HFD or a standard diet. In conclusion, liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of an HFD, and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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

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Imburgio, Michael J; Orr, Joseph M

2018-05-01

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

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

International Nuclear Information System (INIS)

Gou Guokai; Li Guomin; Wang Qunfeng

2011-01-01

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

The use of ice-cream to reduce inferior and liver uptake of 99mTc Sestamibi

International Nuclear Information System (INIS)

Williams, R.C.; Jost, G.M.

2002-01-01

Aim: To determine if ice-cream has any role in reducing the main drawback of sestamibi imaging namely inferior and liver uptake of sestamibi in myocardial imaging. This inferior uptake from, Stomach, Loops of Bowel and Left Lobe of liver can make interpretation difficult Can obscure a defect in the inferior margin of the heart and Hot inferior uptake can produce false adjacent cold defect when using a Fourier kernel. Material and Methods: To remove the confounding factor of various 'stress' regimes adenosine exercise and Dobutamine, only resting Sestamibi scans were examined. Patients where Given ice cream on a stick (ice covered) just prior to injection Imaged at 90 mins post injection of 500 Mbq Tc99m Sestamibi with > 90% purity, using eccentric non-elliptical non circular orbit to maximise resolution, for 18 mins with 2 heads. Processing: Reconstruct (for this purpose) with a butterworth filter of 0.4 and a power factor of 2. Sum all coronal views: Make a rectangular ROI covering the inferior 1/2 or the myocardium. Duplicate this ROI and place at same vertical position over highest activity region of liver. Duplicate region and place immediately underneath cardiac region. Create a BGD region of interest between heart and liver. Data: Ratios of heart to liver and inferior to heart are created with and without background correction. Results: Summary: Ice cream reduces the inferior uptake of Sestamibi by 30%. Ice cream reduces the liver uptake by 14%. Conclusion: Given: The low risk of an ice cream intervention. The high acceptance by patients. The low cost. The effect on inferior uptake. The possible effect on liver uptake. I would recommend the use of Ice Cream for all Myocardial Sestamibi Imaging

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

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Marcos F DosSantos

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

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

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Maria Adele Rueger

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

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

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

2012-10-01

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

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

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

2013-09-01

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

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

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

2016-01-29

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

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

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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.

The Effects of Compensatory Auditory Stimulation and High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Tinnitus Perception - A Randomized Pilot Study.

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Henin, Simon; Fein, Dovid; Smouha, Eric; Parra, Lucas C

2016-01-01

Tinnitus correlates with elevated hearing thresholds and reduced cochlear compression. We hypothesized that reduced peripheral input leads to elevated neuronal gain resulting in the perception of a phantom sound. The purpose of this pilot study was to test whether compensating for this peripheral deficit could reduce the tinnitus percept acutely using customized auditory stimulation. To further enhance the effects of auditory stimulation, this intervention was paired with high-definition transcranial direct current stimulation (HD-tDCS). A randomized sham-controlled, single blind study was conducted in a clinical setting on adult participants with chronic tinnitus (n = 14). Compensatory auditory stimulation (CAS) and HD-tDCS were administered either individually or in combination in order to access the effects of both interventions on tinnitus perception. CAS consisted of sound exposure typical to daily living (20-minute sound-track of a TV show), which was adapted with compressive gain to compensate for deficits in each subject's individual audiograms. Minimum masking levels and the visual analog scale were used to assess the strength of the tinnitus percept immediately before and after the treatment intervention. CAS reduced minimum masking levels, and visual analog scale trended towards improvement. Effects of HD-tDCS could not be resolved with the current sample size. The results of this pilot study suggest that providing tailored auditory stimulation with frequency-specific gain and compression may alleviate tinnitus in a clinical population. Further experimentation with longer interventions is warranted in order to optimize effect sizes.

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

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Irma N. Angulo-Sherman

2017-07-01

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

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

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

2016-06-01

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

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

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

2012-09-15

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

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

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

2015-01-01

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

Subnormothermic ex vivo liver perfusion reduces endothelial cell and bile duct injury after donation after cardiac death pig liver transplantation.

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Knaak, Jan M; Spetzler, Vinzent N; Goldaracena, Nicolas; Boehnert, Markus U; Bazerbachi, Fateh; Louis, Kristine S; Adeyi, Oyedele A; Minkovich, Leonid; Yip, Paul M; Keshavjee, Shaf; Levy, Gary A; Grant, David R; Selzner, Nazia; Selzner, Markus

2014-11-01

An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 × 10(-4) ± 2.6 × 10(-4) cells/μm(2)) but not in CS-treated livers (3.7 × 10(-4) ± 1.3 × 10(-4) cells/μm(2) , P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 ± 10 versus 60 ± 18 μmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation. © 2014 American Association for the Study of Liver Diseases.

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

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

2012-01-01

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

Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

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Daniel P Spiegel

Full Text Available 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.

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

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Orjon Rroji

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

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

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

2011-01-01

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

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

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Constantine Frangakis

2014-04-01

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

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

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Tobias U. Hauser

2013-06-01

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

Two New Chroman Derivations from the Endophytic Penicillium sp. DCS523

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

2011-01-01

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

Reduced size liver transplantation from a donor supported by a Berlin Heart.

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Misra, M V; Smithers, C J; Krawczuk, L E; Jenkins, R L; Linden, B C; Weldon, C B; Kim, H B

2009-11-01

Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

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

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Petteri Hyvärinen

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

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

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

2016-01-15

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

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

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Sung, Kyongje; Gordon, Barry

2018-01-01

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

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

Science.gov (United States)

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

2011-01-18

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

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

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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

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

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

2008-10-01

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

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

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

2014-02-01

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

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

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Andrea eAntal

2014-06-01

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

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

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Toralf eNeuling

2012-09-01

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

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

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Voarino, Nathalie; Dubljević, Veljko; Racine, Eric

2016-01-01

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

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

Science.gov (United States)

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

2016-09-01

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

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

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2010-09-28

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

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

Science.gov (United States)

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

2016-10-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Matzen, Laura E.; Trumbo, Michael Christopher Stefan

2014-10-01

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

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

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Sperling Rhoda

2011-08-01

Full Text Available Abstract Background During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. Methods We compare culture-generated monocyte derived DCs (MDDCs with directly isolated myeloid dendritic cells (mDCs and plasmacytoid dendritic cells (pDCs and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy. Results We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients. Conclusions Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.

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

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

2014-01-01

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

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

Science.gov (United States)

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

2014-01-01

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

Two New Chroman Derivations from the Endophytic Penicillium sp. DCS523

Directory of Open Access Journals (Sweden)

Qi Wang

2011-01-01

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

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

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

2017-01-01

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

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

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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.

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

Science.gov (United States)

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

2017-11-27

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

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

OpenAIRE

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

2010-01-01

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

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

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Xue Zhang

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

Chocolate intake may reduce liver count in 99m-Tc-tetrofosmin myocardial SPECT

International Nuclear Information System (INIS)

Tsunekawa, Akikazu; Yasuda, Eisuke; Okuda, Seiji

2005-01-01

The accumulation of 99m-Tc-Tetrofosmin (TF) in the liver and intestine may often interfere the image quality of myocardial TF SPECT. Although milk intake before acquisition is recommended to reduce its accumulation by enhancing biliary excretion of TF, some patients cannot accept milk. To elucidate the efficacy of chocolate intake as a substitute for milk, we investigated 72 patients with coronary heart disease who underwent TF SPECT (stress imaging; n=36, rest imaging; n=36). Following injection of TF, the patients were randomly treated either with milk (n=24), or chocolate (n=24). The images were acquired before treatment, at 15 min, at 30 min, and 45 min after treatment. The ratio of liver to heart count (LHR) was calculated and was compared between the two groups. LHR in the stress imaging was not significantly different between the milk-treated and chocolate-treated groups: 1.86 vs 1.87 before treatment, 1.39 vs 1.39 at 30 min, and 1.02 vs 1.03 at 45 min. LHR in the rest imaging was also the same between the two groups: 1.43 vs 1.42 before treatment, 1.22 vs 1.21 at 15 min, and 0.95 vs. 0.95 at 30 min. Chocolate intake may be equally effective to milk intake in reducing the liver accumulation of TF. (author)

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

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Karolina M. Lukasik

2018-01-01

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

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

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Ryan eMcKendrick

2015-03-01

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

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

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

2017-08-14

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

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

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

2011-08-01

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

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

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

2014-01-01

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

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

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

2011-01-01

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

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

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Franziska Dambacher

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

Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.

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Gao, Xing; Nan, Yang; Zhao, Yuanlin; Yuan, Yuan; Ren, Bincheng; Sun, Chao; Cao, Kaiyu; Yu, Ming; Feng, Xuyang; Ye, Jing

2017-12-01

Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD). Intriguingly, atorvastatin stimulated the PKA-mediated phosphorylation of Plin5 and reduced the triglyceride (TG) accumulation in hepatocytes with overexpression of wide type (Plin5-WT) compared to serine-155 mutant Plin5 (Plin5-S155A). Moreover, PKA-stimulated FA release of purified LDs carrying Plin5-WT but not Plin5-S155A. Glucagon, a PKA activator, stimulated the phosphorylation of Plin5-WT and inhibited its interaction with CGI-58. The results indicated that atorvastatin promoted lipolysis and reduced TG accumulation in the liver by increasing PKA-mediated phosphorylation of Plin5. This new mechanism of lipid-lowering effects of atorvastatin might provide a new strategy for NAFLD treatment. Copyright © 2017. Published by Elsevier B.V.

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

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Conkin, J; Van Liew, H D

1992-11-01

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

A Randomized Controlled Trial of Lorazepam to Reduce Liver Motion in Patients Receiving Upper Abdominal Radiation Therapy

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Tsang, Derek S.; Voncken, Francine E.M.; Tse, Regina V. [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada); Sykes, Jenna [Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto (Canada); Wong, Rebecca K.S.; Dinniwell, Rob E.; Kim, John; Ringash, Jolie; Brierley, James D.; Cummings, Bernard J.; Brade, Anthony [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada); Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada)

2013-12-01

Purpose: Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion. Methods and Materials: Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy. Results: Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant. Conclusions: Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm.

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

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Demboski, John T.; Pilmanis, Andrew A.

1994-01-01

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

Reduced discomfort during High-Definition transcutaneous stimulation using 6% benzocaine

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Berkan eGuleyupoglu

2014-07-01

Full Text Available AbstractBackground High-Definition transcranial Direct Current Stimulation (HD-tDCS allows for non-invasive neuromodulation using an array of compact (approximately 1 cm2 contact area High-Definition (HD electrodes, as compared to conventional tDCS (which uses two large pads that are approximately 35cm2. In a previous transcutaneous study, we developed and validated designs for HD electrodes that reduce discomfort over >20 min session with 2 mA electrode current.ObjectiveThe purpose of this study was to investigate the use of a chemical pretreatment with 6% benzocaine (topical numbing agent to further reduce subjective discomfort during transcutaneous stimulation and to allow for better sham controlled studies.MethodsPre-treatment with 6% benzocaine was compared with control (no pretreatment for 22 minutes 2 mA of stimulation, with either CCNY-4 or Lectron II electroconductive gel, for both cathodal and anodal transcutaneous (forearm stimulation (8 different combinations.Results Results show that for all conditions and polarities tested, stimulation with HD electrodes is safe and well tolerated and that pretreatment further reduced subjective discomfort. ConclusionPretreatment with a mild analgesic reduces discomfort during HD-tDCS.

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

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

2015-01-01

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

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

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

2016-04-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

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

2008-06-07

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

d-Cycloserine reduces context specificity of sexual extinction learning.

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Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Trimbos, Baptist; Both, Stephanie

2015-11-01

d-Cycloserine (DCS) enhances extinction processes in animals. Although classical conditioning is hypothesized to play a pivotal role in the aetiology of appetitive motivation problems, no research has been conducted on the effect of DCS on the reduction of context specificity of extinction in human appetitive learning, while facilitation hereof is relevant in the context of treatment of problematic reward-seeking behaviors. Female participants were presented with two conditioned stimuli (CSs) that either predicted (CS+) or did not predict (CS-) a potential sexual reward (unconditioned stimulus (US); genital vibrostimulation). Conditioning took place in context A and extinction in context B. Subjects received DCS (125mg) or placebo directly after the experiment on day 1 in a randomized, double-blind, between-subject fashion (Placebo n=31; DCS n=31). Subsequent testing for CS-evoked conditioned responses (CRs) in both the conditioning (A) and the extinction context (B) took place 24h later on day 2. Drug effects on consolidation were then assessed by comparing the recall of sexual extinction memories between the DCS and the placebo groups. Post learning administration of DCS facilitates sexual extinction memory consolidation and affects extinction's fundamental context specificity, evidenced by reduced conditioned genital and subjective sexual responses, relative to placebo, for presentations of the reward predicting cue 24h later outside the extinction context. DCS makes appetitive extinction memories context-independent and prevents the return of conditioned response. NMDA receptor glycine site agonists may be potential pharmacotherapies for the prevention of relapse of appetitive motivation disorders with a learned component. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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Christian Plewnia

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

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

Science.gov (United States)

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

2015-01-01

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

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

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Roy, Abhrajeet; Baxter, Bryan

2014-01-01

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

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

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Guhathakurta, Debarpan; Dutta, Anirban

2016-01-01

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

The antifibrinolytic drug tranexamic acid reduces liver injury and fibrosis in a mouse model of chronic bile duct injury.

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Joshi, Nikita; Kopec, Anna K; Towery, Keara; Williams, Kurt J; Luyendyk, James P

2014-06-01

Hepatic fibrin deposition has been shown to inhibit hepatocellular injury in mice exposed to the bile duct toxicant α-naphthylisothiocyanate (ANIT). Degradation of fibrin clots by fibrinolysis controls the duration and extent of tissue fibrin deposition. Thus, we sought to determine the effect of treatment with the antifibrinolytic drug tranexamic acid (TA) and plasminogen activator inhibitor-1 (PAI-1) deficiency on ANIT-induced liver injury and fibrosis in mice. Plasmin-dependent lysis of fibrin clots was impaired in plasma from mice treated with TA (1200 mg/kg i.p., administered twice daily). Prophylactic TA administration reduced hepatic inflammation and hepatocellular necrosis in mice fed a diet containing 0.025% ANIT for 2 weeks. Hepatic type 1 collagen mRNA expression and deposition increased markedly in livers of mice fed ANIT diet for 4 weeks. To determine whether TA treatment could inhibit this progression of liver fibrosis, mice were fed ANIT diet for 4 weeks and treated with TA for the last 2 weeks. Interestingly, TA treatment largely prevented increased deposition of type 1 collagen in livers of mice fed ANIT diet for 4 weeks. In contrast, biliary hyperplasia/inflammation and liver fibrosis were significantly increased in PAI-1(-/-) mice fed ANIT diet for 4 weeks. Overall, the results indicate that fibrinolytic activity contributes to ANIT diet-induced liver injury and fibrosis in mice. In addition, these proof-of-principle studies suggest the possibility that therapeutic intervention with an antifibrinolytic drug could form a novel strategy to prevent or reduce liver injury and fibrosis in patients with liver disease.

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease.

NARCIS (Netherlands)

Gevers, T.J.G.; Chrispijn, M.; Wetzels, J.F.M.; Drenth, J.P.H.

2012-01-01

BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease.

Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

Science.gov (United States)

Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

2013-01-01

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (PBCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice.

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Henning, Justin R; Graffeo, Christopher S; Rehman, Adeel; Fallon, Nina C; Zambirinis, Constantinos P; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Bin-Saeed, Usama; Rao, Raghavendra S; Badar, Sana; Quesada, Juan P; Acehan, Devrim; Miller, George

2013-08-01

Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen-presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8(+) T-cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. Copyright © 2013 American Association for the Study of Liver Diseases.

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

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Manuel C Olma

2013-06-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

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

2018-02-01

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

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

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

2016-10-28

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

Design of a DCS Based Model for Continuous Leakage Monitoring System of Rotary Air Preheater of a Thermal Power Plant

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Madan BHOWMICK

2011-01-01

Full Text Available The leakage in rotary air preheater makes a considerable contribution to the reduced overall efficiency of fossil-fuel-fired thermal power plants and increase the effect on environment. Since it is normal phenomenon, continuous monitoring of leakage is generally omitted in most power plants. But for accurate analysis of the operation of the thermal power plant, this leakage monitoring plays a vital role. In the present paper, design of a DCS based model for continuous leakages monitoring of rotary air preheater has been described. In the proposed model, the existing DCS based instrumentation system has been modified and online leakage monitoring system has been developed. This model has been installed in a captive power plant with high capacity boilers and very much satisfactory operation of this system has been observed. The observed online data along with their analysis results are presented in this paper.

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

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

2016-03-01

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

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

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Stumbrys, Tadas; Erlacher, Daniel; Schredl, Michael

2013-12-01

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

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

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

2017-09-13

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

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

International Nuclear Information System (INIS)

Shi Weihua; Lu Zhenguo; Xie Qi

2012-01-01

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

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

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

2016-01-04

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

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

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Medina, Jared; Cason, Samuel

2017-09-01

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

Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF on Mouse Liver and Kidney

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Berna Tezcan

2017-12-01

Full Text Available Objective: Brainderived neurotrophic factor (BDNF promotes the development and differentiation of neurons and synapses, as well as neuronal survival, by acting on specific neuronal groups in the central and peripheral nervous systems. However, the direct effect of BDNF on apoptosis in peripheral tissues is not known. The aim of this study was to investigate the relationship between BDNF and apoptosis, and the density and distribution of BDNF receptors in liver and kidney tissues by histological and immunehistochemical methods. Methods: Seven wild-type and 7 BDNF heterozygous (reduced BDNF levels male mice were used in the study. Caspase-3 and TUNEL immunehistochemical stainings were performed in order to investigate the presence of apoptosis in the liver and kidney tissues of the studied groups. Apoptosis-entering cells were counted and the groups were compared. Concentration and distribution of BDNF receptors, tropomyosin-related kinase B (TrkB and nerve growth factor receptor p75 (NGFR p75, in liver and kidney tissues were also examined by immunehistochemical analyzes. Results: As a result of Caspase-3 and TUNEL immune histochemical staining, more cells were counted to enter the apoptotic process in sections of BDNF heterozygous group compared to control group (p<0.0001. In both groups TrkB and NGFR p75 receptors in liver and kidney tissues were determined in trace amounts, but there was no difference in intensity and distribution between the studied groups. Conclusion: According to our histological and immune histochemical stainings and statistical analysis of cell count between groups, it was found that BDNF is protect ive against apoptosis in liver and kidney. The lack of difference between the studied groups in terms of intensity and distribution of BDNF receptors, suggests that BDNF receptor distribution in the liver and kidney tissues may be different from the nervous system or that BDNF may differ in affinity for these receptors.

Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

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Motoh Iwasa

Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

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

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Hyang-Mi Lee

2015-02-01

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

Single-session tDCS over the dominant hemisphere affects contralateral spectral EEG power, but does not enhance neurofeedback-guided event-related desynchronization of the non-dominant hemisphere's sensorimotor rhythm.

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Mondini, Valeria; Mangia, Anna Lisa; Cappello, Angelo

2018-01-01

Transcranial direct current stimulation (tDCS) and neurofeedback-guided motor imagery (MI) have attracted considerable interest in neurorehabilitation, given their ability to influence neuroplasticity. As tDCS has been shown to modulate event-related desynchronization (ERD), the neural signature of motor imagery detected for neurofeedback, a combination of the techniques was recently proposed. One limitation of this approach is that the area targeted for stimulation is the same from which the signal for neurofeedback is acquired. As tDCS may interfere with proximal electroencephalographic (EEG) electrodes, in this study our aim was to test whether contralateral tDCS could have interhemispheric effects on the spectral power of the unstimulated hemisphere, possibly mediated by transcallosal connection, and whether such effects could be used to enhance ERD magnitudes. A contralateral stimulation approach would indeed facilitate co-registration, as the stimulation electrode would be far from the recording sites. Twenty right-handed healthy volunteers (aged 21 to 32) participated in the study: ten assigned to cathodal, ten to anodal versus sham stimulation. We applied stimulation over the dominant (left) hemisphere, and assessed ERD and spectral power over the non-dominant (right) hemisphere. The effect of tDCS was evaluated over time. Spectral power was assessed in theta, alpha and beta bands, under both rest and MI conditions, while ERD was evaluated in alpha and beta bands. Two main findings emerged: (1) contralateral alpha-ERD was reduced after anodal (p = 0.0147), but not enhanced after cathodal tDCS; (2) both stimulations had remote effects on the spectral power of the contralateral hemisphere, particularly in theta and alpha (significant differences in the topographical t-value maps). The absence of contralateral cathodal ERD enhancement suggests that the protocol is not applicable in the context of MI training. Nevertheless, ERD results of anodal and spectral

Diagnostic performance of reduced-dose CT with a hybrid iterative reconstruction algorithm for the detection of hypervascular liver lesions: a phantom study

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Nakamoto, Atsushi; Tanaka, Yoshikazu; Juri, Hiroshi; Nakai, Go; Narumi, Yoshifumi [Osaka Medical College, Department of Radiology, Takatsuki, Osaka (Japan); Yoshikawa, Shushi [Osaka Medical College Hospital, Central Radiology Department, Takatsuki, Osaka (Japan)

2017-07-15

To investigate the diagnostic performance of reduced-dose CT with a hybrid iterative reconstruction (IR) algorithm for the detection of hypervascular liver lesions. Thirty liver phantoms with or without simulated hypervascular lesions were scanned with a 320-slice CT scanner with control-dose (40 mAs) and reduced-dose (30 and 20 mAs) settings. Control-dose images were reconstructed with filtered back projection (FBP), and reduced-dose images were reconstructed with FBP and a hybrid IR algorithm. Objective image noise and the lesion to liver contrast-to-noise ratio (CNR) were evaluated quantitatively. Images were interpreted independently by 2 blinded radiologists, and jackknife alternative free-response receiver-operating characteristic (JAFROC) analysis was performed. Hybrid IR images with reduced-dose settings (both 30 and 20 mAs) yielded significantly lower objective image noise and higher CNR than control-dose FBP images (P <.05). However, hybrid IR images with reduced-dose settings had lower JAFROC1 figure of merit than control-dose FBP images, although only the difference between 20 mAs images and control-dose FBP images was significant for both readers (P <.01). An aggressive reduction of the radiation dose would impair the detectability of hypervascular liver lesions, although objective image noise and CNR would be preserved by a hybrid IR algorithm. (orig.)

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

Science.gov (United States)

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

2016-01-01

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

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

OpenAIRE

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

2014-01-01

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

A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease.

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Trasino, Steven E; Tang, Xiao-Han; Jessurun, Jose; Gudas, Lorraine J

2016-10-01

Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat nonalcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor β2 (RARβ2) and RARγ can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARβ2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of α-smooth muscle actin (α-SMA), in mice with HFD-induced NAFLD. Livers of HFD-fed mice treated with AC261066 exhibited reduced steatosis, oxidative stress, and expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and monocyte chemotactic protein-1 (MCP-1). Kupffer cell (macrophage) expression of transforming growth factor-β1 (TGF-β1), which plays a critical role in early HSC activation, was markedly reduced in AC261066-treated, HFD-fed mice. In contrast, HFD-fed mice treated with an RARγ agonist (CD1530) showed no decreases in steatosis, HSC activation, or Kupffer cell TGF-β1 levels. In conclusion, our data demonstrate that RARβ2 is an attractive target for development of NAFLD therapies. • Hepatic stellate cells (HSCs) are an important pharmacological target for the prevention of nonalcoholic fatty liver diseases (NAFLD). • Retinoids and retinoic acid receptors (RARs) possess favorable metabolic modulating properties. • We show that an agonist for retinoic acid receptor-β2 (RARβ2), but not RARγ, mitigates HSC activation and NAFLD.

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

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

2017-01-15

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

Heat Killed Lactobacillus reuteri GMNL-263 Reduces Fibrosis Effects on the Liver and Heart in High Fat Diet-Hamsters via TGF-β Suppression

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Wei-Jen Ting

2015-10-01

Full Text Available Obesity is one of the major risk factors for nonalcoholic fatty liver disease (NAFLD, and NAFLD is highly associated with an increased risk of cardiovascular disease (CVD. Scholars have suggested that certain probiotics may significantly impact cardiovascular health, particularly certain Lactobacillus species, such as Lactobacillus reuteri GMNL-263 (Lr263 probiotics, which have been shown to reduce obesity and arteriosclerosis in vivo. In the present study, we examined the potential of heat-killed bacteria to attenuate high fat diet (HFD-induced hepatic and cardiac damages and the possible underlying mechanism of the positive effects of heat-killed Lr263 oral supplements. Heat-killed Lr263 treatments (625 and 3125 mg/kg-hamster/day were provided as a daily supplement by oral gavage to HFD-fed hamsters for eight weeks. The results show that heat-killed Lr263 treatments reduce fatty liver syndrome. Moreover, heat-killed Lactobacillus reuteri GMNL-263 supplementation in HFD hamsters also reduced fibrosis in the liver and heart by reducing transforming growth factor β (TGF-β expression levels. In conclusion, heat-killed Lr263 can reduce lipid metabolic stress in HFD hamsters and decrease the risk of fatty liver and cardiovascular disease.

Cooperation Not Competition: Bihemispheric tDCS and fMRI Show Role for Ipsilateral Hemisphere in Motor Learning.

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Waters, Sheena; Wiestler, Tobias; Diedrichsen, Jörn

2017-08-02

What is the role of ipsilateral motor and premotor areas in motor learning? One view is that ipsilateral activity suppresses contralateral motor cortex and, accordingly, that inhibiting ipsilateral regions can improve motor learning. Alternatively, the ipsilateral motor cortex may play an active role in the control and/or learning of unilateral hand movements. We approached this question by applying double-blind bihemispheric transcranial direct current stimulation (tDCS) over both contralateral and ipsilateral motor cortex in a between-group design during 4 d of unimanual explicit sequence training in human participants. Independently of whether the anode was placed over contralateral or ipsilateral motor cortex, bihemispheric stimulation yielded substantial performance gains relative to unihemispheric or sham stimulation. This performance advantage appeared to be supported by plastic changes in both hemispheres. First, we found that behavioral advantages generalized strongly to the untrained hand, suggesting that tDCS strengthened effector-independent representations. Second, functional imaging during speed-matched execution of trained sequences conducted 48 h after training revealed sustained, polarity-independent increases in activity in both motor cortices relative to the sham group. These results suggest a cooperative rather than competitive interaction of the two motor cortices during skill learning and suggest that bihemispheric brain stimulation during unimanual skill learning may be beneficial because it harnesses plasticity in the ipsilateral hemisphere. SIGNIFICANCE STATEMENT Many neurorehabilitation approaches are based on the idea that is beneficial to boost excitability in the contralateral hemisphere while attenuating that of the ipsilateral cortex to reduce interhemispheric inhibition. We observed that bihemispheric transcranial direct current stimulation (tDCS) with the excitatory anode either over contralateral or ipsilateral motor cortex

Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

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Gerth, Hans U; Pohlen, Michele; Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Hüsing-Kabar, Anna; Wilms, Christian; Maschmeier, Miriam; Kabar, Iyad; Torner, Josep; Pavesi, Marco; Arroyo, Vicente; Banares, Rafael; Schmidt, Hartmut H J

2017-10-01

Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Medical Departments of University Hospital Muenster (Germany). This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1-3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Standard medical treatment and molecular adsorbent recirculating system. Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2-3). Concerning the

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

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

2015-10-01

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

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

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Christina eArtemenko

2015-03-01

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

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

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

2013-01-01

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

Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE: study protocol for a randomized controlled trial

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Chrispijn Melissa

2011-11-01

Full Text Available Abstract Background Polycystic liver disease (PLD is defined as having more than 20 liver cysts and can present as a severe and disabling condition. Most symptoms are caused by the mass effect of the liver size and include abdominal pain and distension. The somatostatin analogues octreotide and lanreotide have proven to reduce polycystic liver volume. mTOR inhibitors such as everolimus inhibit cell proliferation and might thereby reduce growth of liver cysts. This trial aims to assess the benefit of combination therapy of everolimus and octreotide compared to octreotide monotherapy. In this study we present the structure of the trial and the characteristics of the included patients. Methods/design This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed. Discussion This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume. Trial registration number ClinicalTrials.gov: NCT01157858

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

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Jinyi Hung

2017-05-01

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

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

Science.gov (United States)

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

2017-01-01

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

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

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

2015-12-26

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

Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

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Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

2015-01-01

In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis.

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Ray, Jessica L; Kopec, Anna K; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H; Williams, Kurt J; Leung, Patrick S; Gershwin, M Eric; Luyendyk, James P

2017-04-01

Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL+/+ mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

NARCIS (Netherlands)

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

2016-01-01

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

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

Science.gov (United States)

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

2012-01-01

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

Neuromodulation directed at the prefrontal cortex of subjects with obesity reduces snack food intake and hunger in a randomized trial.

Science.gov (United States)

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

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

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

2016-01-01

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

Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity

International Nuclear Information System (INIS)

Kwasnicka-Crawford, Dorota A.; Vincent, Steven R.

2005-01-01

Microsomal cytochrome P450 reductase catalyzes the one-electron transfer from NADPH via FAD and FMN to various electron acceptors, such as cytochrome P450s or to some anti-cancer quinone drugs. This results in generation of free radicals and toxic oxygen metabolites, which can contribute to the cytotoxicity of these compounds. Recently, a cytosolic NADPH-dependent flavin reductase, NR1, has been described which is highly homologous to the microsomal cytochrome P450 reductase. In this study, we show that over-expression of NR1 in human embryonic kidney cells enhances the cytotoxic action of the model quinone, menadione. Furthermore, we show that a novel human histidine triad protein DCS-1, which is expressed together with NR1 in many tissues, can significantly reduce menadione-induced cytotoxicity in these cells. We also show that DCS-1 binds NF1 and directly modulates its activity. These results suggest that NR1 may play a role in carcinogenicity and cell death associated with one-electron reductions

Comparative analysis on the effect of Lycopersicon esculentum (tomato) in reducing cadmium, mercury and lead accumulation in liver.

Science.gov (United States)

Nwokocha, Chukwuemeka R; Nwokocha, Magdalene I; Aneto, Imaria; Obi, Joshua; Udekweleze, Damian C; Olatunde, Bukola; Owu, Daniel U; Iwuala, Moses O

2012-06-01

L. esculentum (tomato) contain compounds with anti-oxidant and anti-inflammatory properties, able to synthesize metal chelating proteins. We examined the ability of fruit extract to protect against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. Rats were fed on tomato mixed with rat chow (10% w/w), while Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) was given in drinking water. Tomato was administered together with the metals (group 2), a week after exposure (group 3) or a week before metal exposure (group 4) for a period of six weeks. The metal accumulations in the liver were determined using AAS. There was a significant (Ptomato to Cd and Hg accumulation but not to Pb (PTomato reduces uptake while enhancing the elimination of these metals in a time dependent manner. The highest hepatoprotective effect was to Cd followed by Hg and least to Pb. Its administration is beneficial in reducing heavy metal accumulation in the liver. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-10-15

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

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

International Nuclear Information System (INIS)

Pollet, J.

2006-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2006-07-01

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

A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

International Nuclear Information System (INIS)

Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol; Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk

2008-01-01

To assess the toxicity and tumor response induced by DCVac/IR dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6x10 6 DCs were packed into a vial (DCVac/IR, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3x10 6 to 12x10 6 DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Of the 24 registered patients, 22 received the DCs injections. Moreover

A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

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Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol [Donga Univ. School of Medicine, Busan (Korea, Republic of); Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk [Busan National University College of Medicine, Busan (Korea, Republic of)

2008-06-15

To assess the toxicity and tumor response induced by DCVac/IR dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6x10{sup 6} DCs were packed into a vial (DCVac/IR, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3x10{sup 6} to 12x10{sup 6} DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Of the 24 registered patients, 22 received the DCs

Extracellular ATP reduces HIV-1 transfer from immature dendritic cells to CD4+ T lymphocytes

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Barat Corinne

2008-03-01

Full Text Available Abstract Background Dendritic cells (DCs are considered as key mediators of the early events in human immunodeficiency virus type 1 (HIV-1 infection at mucosal sites. Previous studies have shown that surface-bound virions and/or internalized viruses found in endocytic vacuoles of DCs are efficiently transferred to CD4+ T cells. Extracellular adenosine triphosphate (ATP either secreted or released from necrotic cells induces a distorted maturation of DCs, transiently increases their endocytic capacity and affects their migratory capacity. Knowing that high extracellular ATP concentrations are present in situations of tissue injury and inflammation, we investigated the effect of ATP on HIV-1 transmission from DCs to CD4+ T lymphocytes. Results In this study, we show that extracellular ATP reduces HIV-1 transfer from immature monocyte-derived DCs (iDCs to autologous CD4+ T cells. This observed decrease in viral replication was related to a lower proportion of infected CD4+ T cells following transfer, and was seen with both X4- and R5-tropic isolates of HIV-1. Extracellular ATP had no effect on direct CD4+ T cell infection as well as on productive HIV-1 infection of iDCs. These observations indicate that extracellular ATP affects HIV-1 infection of CD4+ T cells in trans with no effect on de novo virus production by iDCs. Additional experiments suggest that extracellular ATP might modulate the trafficking pathway of internalized virions within iDCs leading to an increased lysosomal degradation, which could be partly responsible for the decreased HIV-1 transmission. Conclusion These results suggest that extracellular ATP can act as a factor controlling HIV-1 propagation.

Cerebellar tDCS does not improve performance in probabilistic classification learning

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

2016-01-01

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

Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

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Marta Moya

Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

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

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

2016-01-01

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

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

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

2015-01-01

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

Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

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Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

2016-03-15

Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

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.

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

2017-01-01

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

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

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

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

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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.

Transcranial direct current stimulation (tDCS) reveals a dissociation between SNARC and MARC effects: Implication for the polarity correspondence account.

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Di Rosa, Elisa; Bardi, Lara; Umiltà, Carlo; Masina, Fabio; Forgione, Margherita; Mapelli, Daniela

2017-08-01

The concept of stimulus response compatibility (SRC) refers to the existence of a privileged association between a specific stimulus feature and a specific response feature. Two examples of SRC are the Spatial Numerical Association of Response Codes (SNARC) and the Markedness Association of Response Codes (MARC) effects. According to the polarity correspondence principle, these two SRC effects occur because of a match between the most salient dimensions of stimulus and response. Specifically, the SNARC effect would be caused by a match between right-sided responses and large numbers, while a match between right-sided responses and even numbers would give rise to the MARC effect. The aim of the present study was to test the validity of the polarity correspondence principle in explaining these two SRC effects. To this end, we applied transcranial direct current stimulation (tDCS) over left and right posterior parietal cortex (PPC), which is thought to be the neural basis of salience processing, during a parity judgement task. Results showed that cathodal tDCS over the PPC significantly reduced the MARC effect but did not affect the SNARC effect, suggesting a dissociation between the two effects. That is, the MARC would rely on a salience processing mechanism, whereas the SNARC would not. Despite this interpretation is in need of further experimental confirmations (i.e., testing different tasks or using different tDCS montages), our results suggest that the polarity correspondence principle can be a plausible explanation only for the MARC effect but not for the SNARC effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

2017-02-01

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

Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.

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Delgado, María Gabriela; Gracia-Sancho, Jordi; Marrone, Giusi; Rodríguez-Vilarrupla, Aina; Deulofeu, Ramon; Abraldes, Juan G; Bosch, Jaume; García-Pagán, Juan Carlos

2013-10-01

Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.

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

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

2016-10-01

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

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

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Alexander Brunnauer

2018-01-01

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

Evaluation of Protective Activity of Curcumin in Reducing Methotrexate Induced Liver Cells Injury: An Experimental Study on Iraqi White Domestic Rabbits

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Hussain Abady Aljebori

2018-03-01

Full Text Available Background: Hepatotoxicity is a common problem in medical practice, most of the commonly used drugs are potentially hepatotoxic. Although Methotrexate is a hepa- toxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin con- tains a variety of natural substances with antioxidant properties, it is widely used in  folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration. Objective: The research aims to study the methotrexate hepatoxicity on rabbits, and the hepatoprotective activity of Curcumin. Materials and Methods: Thirty white domestic rabbits were bought from animal market and grouped randomly into three groups; control group received intraperitoneal normal saline, methotrexate group received 6.5 mg/Kgm body weight intraperitoneal methotrexate, and curcumin group received oral Curcumin in addition to intraperitoneal methotrexate. Results: The study showed abnormal liver function tests, INR, liver tissues oxida- tive markers, and liver cell injury on histopathology in Methotrexate group, and normal findings in Curcumin groups. Conclusion: It is concluded that the Methotrexate is a hepatotoxic drug. The results also shoe that the concomitant administration of Curcumin reduced hepatotoxicity. Recommendation: It is recommended to use of Curcumin in clinical practice as a food supplement to patient receiving methotrexate to reduce hepatotoxicity.

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

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

2015-08-01

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

Transcranial direct current stimulation (tDCS) Paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: a pilot study.

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Potter-Baker, Kelsey A; Janini, Daniel P; Lin, Yin-Liang; Sankarasubramanian, Vishwanath; Cunningham, David A; Varnerin, Nicole M; Chabra, Patrick; Kilgore, Kevin L; Richmond, Mary Ann; Frost, Frederick S; Plow, Ela B

2017-08-07

Objective Our goal was to determine if pairing transcranial direct current stimulation (tDCS) with rehabilitation for two weeks could augment adaptive plasticity offered by these residual pathways to elicit longer-lasting improvements in motor function in incomplete spinal cord injury (iSCI). Design Longitudinal, randomized, controlled, double-blinded cohort study. Setting Cleveland Clinic Foundation, Cleveland, Ohio, USA. Participants Eight male subjects with chronic incomplete motor tetraplegia. Interventions Massed practice (MP) training with or without tDCS for 2 hrs, 5 times a week. Outcome Measures We assessed neurophysiologic and functional outcomes before, after and three months following intervention. Neurophysiologic measures were collected with transcranial magnetic stimulation (TMS). TMS measures included excitability, representational volume, area and distribution of a weaker and stronger muscle motor map. Functional assessments included a manual muscle test (MMT), upper extremity motor score (UEMS), action research arm test (ARAT) and nine hole peg test (NHPT). Results We observed that subjects receiving training paired with tDCS had more increased strength of weak proximal (15% vs 10%), wrist (22% vs 10%) and hand (39% vs. 16%) muscles immediately and three months after intervention compared to the sham group. Our observed changes in muscle strength were related to decreases in strong muscle map volume (r=0.851), reduced weak muscle excitability (r=0.808), a more focused weak muscle motor map (r=0.675) and movement of weak muscle motor map (r=0.935). Conclusion Overall, our results encourage the establishment of larger clinical trials to confirm the potential benefit of pairing tDCS with training to improve the effectiveness of rehabilitation interventions for individuals with SCI. Trial Registration NCT01539109.

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.

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Henrique Borges da Silva

2015-02-01

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

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

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

2015-02-01

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

A simultaneous modulation of reactive and proactive inhibition processes by anodal tDCS on the right inferior frontal cortex.

Directory of Open Access Journals (Sweden)

Toni Cunillera

Full Text Available Proactive and reactive inhibitory processes are a fundamental part of executive functions, allowing a person to stop inappropriate responses when necessary and to adjust performance in in a long term in accordance to the goals of a task. In the current study, we manipulate, in a single task, both reactive and proactive inhibition mechanisms, and we investigate the within-subjects effect of increasing, by means of anodal transcranial direct current stimulation (tDCS, the involvement of the right inferior frontal cortex (rIFC. Our results show a simultaneous enhancement of these two cognitive mechanisms when modulating the neural activity of rIFC. Thus, the application of anodal tDCS increased reaction times on Go trials, indicating a possible increase in proactive inhibition. Concurrently, the stop-signal reaction time, as a covert index of the inhibitory process, was reduced, demonstrating an improvement in reactive inhibition. In summary, the current pattern of results validates the engagement of the rIFC in these two forms of inhibitory processes, proactive and reactive inhibition and it provides evidence that both processes can operate concurrently in the brain.

Total non-imaging in liver scintiscanning in case of alcoholic liver cirrhosis

Energy Technology Data Exchange (ETDEWEB)

Schlicht, I; Roh, T

1983-01-01

Case reports are given of 3 female patients suffering from advanced, hypertrophic alcoholic cirrhosis of the liver with portal hypertension. The livers of these patients were not demonstrable by scintigraphy. The patients died a few months afterwards from liver failure. This syndrome - failure of the liver to show up in scintigraphy - may have diagnostic and prognostic implications; it may be caused by deficient blood circulation and by reduced phagocytic capacity of the kupfer cell system.

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

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

2017-08-01

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

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

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

2013-11-01

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

Reducing liver fluke transmission in northeastern Thailand | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2016-04-29

Apr 29, 2016 ... ... leaders, local health officials, school teachers—were agents of change. ... visited 186 households and organized liver fluke campaigns in local schools, ... The Lawa Model has since gained national and international ...

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

Science.gov (United States)

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

2016-11-01

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

Anodal tDCS of dorsolateral prefontal cortex during an Implicit Association Test

NARCIS (Netherlands)

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

2012-01-01

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

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

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

2010-12-01

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

Reducing liver transplant length of stay: a Lean Six Sigma approach.

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Toledo, Alexander H; Carroll, Tracy; Arnold, Emily; Tulu, Zeynep; Caffey, Tom; Kearns, Lauren E; Gerber, David A

2013-12-01

Organ transplant centers are under increasing scrutiny to maintain outcomes while controlling cost in a challenging population of patients. Throughout health care and transplant specifically, length of stay is used as a benchmark for both quality and resource utilization. To decrease our length of stay for liver transplant by using Lean Six Sigma methods. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to systematically analyze our process from transplant listing to hospital discharge after transplant, identifying many factors affecting length of stay. Adult, single-organ, primary liver transplant recipients between July 2008 and June 2012 were included in the study. Recipients with living donors or fulminant liver failure were excluded. Multiple interventions, including a clinical pathway and enhanced communication, were implemented. Length of stay after liver transplant and readmission after liver transplant.R ESULTS: Median length of stay decreased significantly from 11 days before the intervention to 8 days after the intervention. Readmission rate did not change throughout the study. The improved length of stay was maintained for 24 months after the study. Using a Lean Six Sigma approach, we were able to significantly decrease the length of stay of liver transplant patients. These results brought our center's outcomes in accordance with our goal and industry benchmark of 8 days. Clear expectations, improved teamwork, and a multidisciplinary clinical pathway were key elements in achieving and maintaining these gains.

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

International Nuclear Information System (INIS)

Zhang Dongwei; Li Yunjian; Li Xiangjian

2012-01-01

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

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

Science.gov (United States)

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

2018-06-05

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

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

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Bita eVaseghi

2015-09-01

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

Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice.

Science.gov (United States)

Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U

2018-01-01

In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN

Diffuse correlation spectroscopy (DCS) study of blood flow changes during low level laser therapy (LLLT): a preliminary report

Science.gov (United States)

Soni, Sagar; Wang, Xinlong; Liu, Hanli; Tian, Fenghua

2017-02-01

Photobiomodulation with low-power, high-fluence light in the near-infrared range (600-1100nm), also known as low level laser therapy (LLLT), has been used for promoting healing of wounds, reducing pain, and so on. Understanding its physiological effect is essential for treatment optimization and evaluation. In this study, we used diffuse correlation spectroscopy (DCS) to investigate the changes of regional blood flow in skeletal muscle induced by a single session of LLLT. DCS is an emerging optical modality to probe microvascular blood flow in human tissues in vivo. We have developed a software-based autocorrelator system with the benefits such as flexibility in raw photon count data processing, portability and low cost. LLLT was administered at the human forearm with a 1064-nm, continuous-wave laser. The emitting power was 3.4 W in an area of 13.6 cm2, corresponding to 0.25W/cm2 irradiance. The emitting duration was 10 minutes. Eight healthy adults of any ethnic background, in an age range of 18-40 years old were included. The results indicate that LLLT causes reliable changes in regional blood flow. However, it remains unclear whether these changes are physiological or attributed to the heating effect of the stimulation laser.

Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

Directory of Open Access Journals (Sweden)

Yumin Xu

Full Text Available Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF.Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations.Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats.sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

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

Science.gov (United States)

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

2017-04-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

Science.gov (United States)

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

2017-12-01

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

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

Science.gov (United States)

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.

Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.

Science.gov (United States)

Tahan, Veysel; Ozaras, Resat; Canbakan, Billur; Uzun, Hafize; Aydin, Seval; Yildirim, Beytullah; Aytekin, Huseyin; Ozbay, Gulsen; Mert, Ali; Senturk, Hakan

2004-09-01

Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

Alcohol extract of North American ginseng (Panax quinquefolius) reduces fatty liver, dyslipidemia, and other complications of metabolic syndrome in a mouse model.

Science.gov (United States)

Singh, Ratnesh K; Lui, Edmund; Wright, David; Taylor, Adrian; Bakovic, Marica

2017-09-01

We investigated whether North American ginseng (Panax quinquefolius) could reduce development of the metabolic syndrome phenotype in a mouse model (ETKO) of the disease. Young ETKO mice have no disease but similar to humans start to develop the fatty liver, hypertriglyceridemia, obesity, and insulin resistance at 25-30 weeks of age, and the disease continues to progress with ageing. ETKO mice were orally given an ethanol extract of ginseng roots at 4 and 32 weeks of age. Treatments with ginseng eliminated the ETKO fatty liver, reduced hepatic and intestinal lipoprotein secretion, and reduced the level of circulating lipids. Improvements by ginseng treatments were manifested as a reduction in the expression of genes involved in the regulation of fatty acid and triglyceride (fat) synthesis and secretion by the lipoproteins on one hand, and the stimulation of fatty acid oxidation and triglyceride degradation by lipolysis on the other hand. These processes altogether improved glucose, fatty acid, and triglyceride metabolism, reduced liver fat load, and reversed the progression of metabolic syndrome. These data confirm that treatments with North American ginseng could alleviate metabolic syndrome through the maintenance of a better balance between glucose and fatty acid metabolism, lipoprotein secretion, and energy homeostasis in disease-prone states.

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

Science.gov (United States)

Deike, Susann; Deliano, Matthias; Brechmann, André

2016-10-01

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

Restrictive blood transfusion protocol in liver resection patients reduces blood transfusions with no increase in patient morbidity.

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Wehry, John; Cannon, Robert; Scoggins, Charles R; Puffer, Lisa; McMasters, Kelly M; Martin, Robert C G

2015-02-01

Management of anemia in surgical oncology patients remains one of the key quality components in overall care and cost. Continued reports demonstrate the effects of hospital transfusion, which has been demonstrated to lead to a longer length of stay, more complications, and possibly worse overall oncologic outcomes. The hypothesis for this study was that a dedicated restrictive transfusion protocol in patients undergoing hepatectomy would lead to less overall blood transfusion with no increase in overall morbidity. A cohort study was performed using our prospective database from January 2000 to June 2013. September 2011 served as the separation point for the date of operation criteria because this marked the implementation of more restrictive blood transfusion guidelines. A total of 186 patients undergoing liver resection were reviewed. The restrictive blood transfusion guidelines reduced the percentage of patients that received blood from 31.0% before January 9, 2011 to 23.3% after this date (P = .03). The liver procedure that was most consistently associated with higher levels of transfusion was a right lobectomy (16%). Prior surgery and endoscopic stent were the 2 preoperative interventions associated with receiving blood. Patients who received blood before and after the restrictive period had similar predictive factors: major hepatectomies, higher intraoperative blood loss, lower preoperative hemoglobin level, older age, prior systemic chemotherapy, and lower preoperative nutritional parameters (all P blood did not have worse overall progression-free survival or overall survival. A restrictive blood transfusion protocol reduces the incidence of blood transfusions and the number of packed red blood cells transfused. Patients who require blood have similar preoperative and intraoperative factors that cannot be mitigated in oncology patients. Restrictive use of blood transfusions can reduce cost and does adversely affect patients undergoing liver resection

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation.

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Gopinathan Pillai Sreekanth

Full Text Available Dengue virus (DENV infection causes organ injuries, and the liver is one of the most important sites of DENV infection, where viral replication generates a high viral load. The molecular mechanism of DENV-induced liver injury is still under investigation. The mitogen activated protein kinases (MAPKs, including p38 MAPK, have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo role of p38 MAPK in DENV-induced liver injury is not fully understood. In this study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse model of DENV infection. Both the hematological parameters, leucopenia and thrombocytopenia, were improved by SB203580 treatment and liver transaminases and histopathology were also improved. We used a real-time PCR microarray to profile the expression of apoptosis-related genes. Tumor necrosis factor α, caspase 9, caspase 8, and caspase 3 proteins were significantly lower in the SB203580-treated DENV-infected mice than that in the infected control mice. Increased expressions of cytokines including TNF-α, IL-6 and IL-10, and chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 treatment. DENV infection induced the phosphorylation of p38MAPK, and its downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did not decrease the phosphorylation of p38 MAPK, but it significantly reduced the phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the downstream signals to p38 MAPK and reduces DENV-induced liver injury.

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

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

2018-02-01

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

Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories.

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Paulo S Boggio

Full Text Available A recent study found that false memories were reduced by 36% when low frequency repetitive transcranial magnetic stimulation (rTMS was applied to the left anterior temporal lobe after the encoding (study phase. Here we were interested in the consequences on a false memory task of brain stimulation throughout the encoding and retrieval task phases. We used transcranial direct current stimulation (tDCS because it has been shown to be a useful tool to enhance cognition. Specifically, we examined whether tDCS can induce changes in a task assessing false memories. Based on our preliminary results, three conditions of stimulation were chosen: anodal left/cathodal right anterior temporal lobe (ATL stimulation ("bilateral stimulation"; anodal left ATL stimulation (with a large contralateral cathodal electrode--referred as "unilateral stimulation" and sham stimulation. Our results showed that false memories were reduced significantly after the two active conditions (unilateral and bilateral stimulation as compared with sham stimulation. There were no significant changes in veridical memories. Our findings show that false memories are reduced by 73% when anodal tDCS is applied to the anterior temporal lobes throughout the encoding and retrieval stages, suggesting a possible strategy for improving certain aspects of learning.

Aryl Hydrocarbon Receptor Activation Reduces Dendritic Cell Function during Influenza Virus Infection

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Jin, Guang-Bi; Moore, Amanda J.; Head, Jennifer L.; Neumiller, Joshua J.; Lawrence, B. Paige

2010-01-01

It has long been known that activation of the aryl hydrocarbon receptor (AhR) by ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses T cell–dependent immune responses; however, the underlying cellular targets and mechanism remain unclear. We have previously shown that AhR activation by TCDD reduces the proliferation and differentiation of influenza virus–specific CD8+ T cells through an indirect mechanism; suggesting that accessory cells are critical AhR targets during infection. Respiratory dendritic cells (DCs) capture antigen, migrate to lymph nodes, and play a key role in activating naive CD8+ T cells during respiratory virus infection. Herein, we report an examination of how AhR activation alters DCs in the lung and affects their trafficking to and function in the mediastinal lymph nodes (MLN) during infection with influenza virus. We show that AhR activation impairs lung DC migration and reduces the ability of DCs isolated from the MLN to activate naive CD8+ T cells. Using novel AhR mutant mice, in which the AhR protein lacks its DNA-binding domain, we show that the suppressive effects of TCDD require that the activated AhR complex binds to DNA. These new findings suggest that AhR activation by chemicals from our environment impacts DC function to stimulate naive CD8+ T cells and that immunoregulatory genes within DCs are critical targets of AhR. Moreover, our results reinforce the idea that environmental signals and AhR ligands may contribute to differential susceptibilities and responses to respiratory infection. PMID:20498003

Reduced 99mTc labelled NCA-95/CEA-antibody uptake in liver due to gentle antibody reconstitution

International Nuclear Information System (INIS)

Reske, S.N.; Buell, U.

1990-01-01

The influence of reconstituting a murine monoclonal IgG 1 antibody kit with pertechnetate Tc99m on antibody distribution in the liver, spleen and sternal bone marrow of patients was examined. The 99m Tc-labelled antibody used is directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen (CEA) and has been successfully applied for imaging tissue inflammation and bone marrow scanning. Radioactivity uptake was determined in the liver, spleen, bone marrow and a precordial background region in a consecutive series of 25 patients, examined with an antibody preparation, routinely radiolabelled according to the manufacturer's recommendations and in 14 patients, in whom the antibody was reconstituted with special care, avoiding bubble formation and dropping of buffer into the antibody-containing vial. Gentle compared with routine antibody reconstitution caused a highly significant reduction of the antibody uptake in the liver, as determined by count densities, normalized to injected dose and acquisition time (13.2±5.5 vs 20.1±6.0 cpm per pixel, anti x±SD, P=0.008). The liver to background ratio was reduced from 3.4±1.4 to 1.9±0.5 (P<0.001). Spleen, sternal bone marrow and precordial background count rates were not significantly affected. These results clearly demonstrate that gentle antibody reconstitution can decrease non-specific antibody uptake in the liver by 34%±6.4% (anti x±SEM). Thus, scan quality is improved, and the potential deleterious camouflage of underlying structures is avoided. (orig.)

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

Science.gov (United States)

2014-01-01

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

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

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

2016-09-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

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

2017-04-01

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

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

International Nuclear Information System (INIS)

Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J.

2014-01-01

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na + -K + -ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na + -K + -ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na + -K + -ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis

Posttraumatic levels of liver enzymes can reduce the need for CT in children

DEFF Research Database (Denmark)

Bruhn, Peter James; Østerballe, Lene; Hillingsø, Jens

2016-01-01

alternative diagnostic modalities. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic enzymes, which are elevated in peripheral blood in relation to liver injury. The aim of the present study was to investigate a potential role of normal liver transaminase levels in the decision......BACKGROUND: Computed tomography (CT) is the gold standard in the initial evaluation of the hemodynamically stable patient with suspected liver trauma. However, the adverse effects of radiation exposure are of specific concern in the pediatric population. It is therefore desirable to explore...... algorithm in suspected pediatric blunt liver trauma. METHODS: Retrospective analysis of consecutively collected data from children (0-17 years) with blunt liver trauma, admitted to a single trauma centre in Denmark, between 2000 and 2013. Patients underwent abdominal CT during initial evaluation...

Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation.

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Cheong, Jaeyoun; Galanko, Joseph A; Arora, Sumant; Cabezas, Joaquin; Ndugga, Nambi J; Lucey, Michael R; Hayashi, Paul H; Barritt, Alfred Sidney; Bataller, Ramon

2017-02-01

Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P renal failure was less marked in patients with ALD (HR = 1.31, P renal failure had better long-term prognosis than non-ALD patients. Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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Amanda Ellison

2017-09-01

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

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.

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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.

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

Directory of Open Access Journals (Sweden)

Z.G. Zhao

2014-02-01

Full Text Available The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL on lipopolysaccharide (LPS-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1, myeloperoxidase (MPO, and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

Energy Technology Data Exchange (ETDEWEB)

Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J. [Institute of Microcirculation, Hebei North University, Zhangjiakou, China, Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei (China)

2014-02-17

The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na{sup +}-K{sup +}-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na{sup +}-K{sup +}-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na{sup +}-K{sup +}-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

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

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Luanda Collange Grecco

2016-07-01

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

Users` demands narrow PLC-DCS gap

Energy Technology Data Exchange (ETDEWEB)

La Fauci, J.

1997-02-01

Supervisory control and data acquisition (SCADA) operator interface (OI) software has propelled programmable logic controllers (PLCs) into areas where they can successfully compete with distributed control systems (DCSs) for many control applications. As a result, automation engineers are struggling to develop guidelines to help determine which is best for batch operations and other applications. There is no clear answer to this issue. There are, however, decision tools such as Kepner-Tregoe (K-T) that can be applied by engineers as a structured approach to decision analysis and system selection. Other factors such as business environment, pressure to reduce project cost, validation, and predicting new technology direction all play a critical role for engineers in choosing between a PLC- or DCS-based control system. Higher-level business issues, however, are seldom considered by engineers during control system selection. Engineers should try to better understand their company`s business objectives and mission statement and how company business direction may affect control system selection. For instance, the pharmaceutical industry can be broken up into the following five basic application groups: bulk chemicals, finishing, biotech, pilot plant, and utilities. Each has a unique set of functional and process-control requirements. Understanding needs and differences of these five basic application groups and applying the optimum control system solution will place the company in a more competitive position. A financial analysis should be one of the first steps in the control system evaluation process. This may include early agreement of contractual terms and conditions as well as a nondisclosure agreement. Other financial considerations may include requesting a financial report on the control system manufacturer or systems integrator that will be performing the work to determine its financial stability. 3 figs.

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

Science.gov (United States)

Doeltgen, Sebastian H; Young, Jessica; Bradnam, Lynley V

2016-08-01

The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

Using Transcranial tDCS to test cognitive hypotheses

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Nazbanou Nozari

2014-04-01

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

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

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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.

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

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Gabriel A. de Lara

2017-08-01

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

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

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Jianbiao Li

2017-06-01

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

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

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

2015-01-01

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

Effect of airplane transport of donor livers on post-liver transplantation survival.

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Huang, Yi; MacQuillan, Gerry; Adams, Leon A; Garas, George; Collins, Megan; Nwaba, Albert; Mou, Linjun; Bulsara, Max K; Delriviere, Luc; Jeffrey, Gary P

2016-11-07

To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver ( P = 0.027). Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

SU-F-T-121: Abdominal Compression Effectively Reduces the Interplay Effect and Enables Pencil Beam Scanning Proton Therapy of Liver Tumors

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Souris, K; Glick, A; Kang, M; Lin, H; McDonough, J; Simone, C; Solberg, T; Ben-Josef, E; Lin, L; Janssens, G; Sterpin, E; Lee, J

2016-01-01

Purpose: To study if abdominal compression can reduce breathing motion and mitigate interplay effect in pencil beam scanning proton therapy (PBSPT) treatment of liver tumors in order to better spare healthy liver volumes compared with photon therapy. Methods: Ten patients, six having large tumors initially treated with IMRT and four having small tumors treated with SBRT, were replanned for PBSPT. ITV and beam-specific PTVs based on 4D-CT were used to ensure target coverage in PBSPT. The use of an abdominal compression belt and volumetric repainting was investigated to mitigate the interplay effect between breathing motion and PBSPT dynamic delivery. An in-house Matlab script has been developed to simulate this interplay effect. The dose is computed on each phase individually by sorting all spots according to their simulated delivery timing. The final dose distribution is then obtained by accumulating all dose maps to a reference phase. Results: For equivalent target coverage PBSPT reduced average healthy liver dose by 9.5% of the prescription dose compared with IMRT/SBRT. Abdominal compression of 113.2±42.2 mmHg was effective for all 10 patients and reduced average motion by 2.25 mm. As a result, the average ITV volume decreased from 128.2% to 123.1% of CTV volume. Similarly, the average beam-specific PTV volume decreased from 193.2% to 183.3%. For 8 of the 10 patients, the average motion was reduced below 5 mm, and up to 3 repainting were sufficient to mitigate interplay. For the other two patients with larger residual motion, 4–5 repainting were needed. Conclusion: We recommend evaluation of the 4DCT motion histogram following simulation and the interplay effect following treatment planning in order to personalize the use of compression and volumetric repainting for each patient. Abdominal compression enables safe and more effective PBS treatment of liver tumors by reduction of motion and interplay effect. Kevin Souris is supported by IBA and Televie Grant

SU-F-T-121: Abdominal Compression Effectively Reduces the Interplay Effect and Enables Pencil Beam Scanning Proton Therapy of Liver Tumors

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Souris, K [Universite catholique de Louvain, Brussels (Belgium); University of Pennsylvania, Philadelphia, PA (United States); Glick, A; Kang, M; Lin, H; McDonough, J; Simone, C; Solberg, T; Ben-Josef, E; Lin, L [University of Pennsylvania, Philadelphia, PA (United States); Janssens, G [IBA, Louvain-la-neuve (Belgium); Sterpin, E [Universite catholique de Louvain, Brussels (Belgium); KU Leuven, Leuven (Belgium); Lee, J [Universite catholique de Louvain, Brussels (Belgium)

2016-06-15

Purpose: To study if abdominal compression can reduce breathing motion and mitigate interplay effect in pencil beam scanning proton therapy (PBSPT) treatment of liver tumors in order to better spare healthy liver volumes compared with photon therapy. Methods: Ten patients, six having large tumors initially treated with IMRT and four having small tumors treated with SBRT, were replanned for PBSPT. ITV and beam-specific PTVs based on 4D-CT were used to ensure target coverage in PBSPT. The use of an abdominal compression belt and volumetric repainting was investigated to mitigate the interplay effect between breathing motion and PBSPT dynamic delivery. An in-house Matlab script has been developed to simulate this interplay effect. The dose is computed on each phase individually by sorting all spots according to their simulated delivery timing. The final dose distribution is then obtained by accumulating all dose maps to a reference phase. Results: For equivalent target coverage PBSPT reduced average healthy liver dose by 9.5% of the prescription dose compared with IMRT/SBRT. Abdominal compression of 113.2±42.2 mmHg was effective for all 10 patients and reduced average motion by 2.25 mm. As a result, the average ITV volume decreased from 128.2% to 123.1% of CTV volume. Similarly, the average beam-specific PTV volume decreased from 193.2% to 183.3%. For 8 of the 10 patients, the average motion was reduced below 5 mm, and up to 3 repainting were sufficient to mitigate interplay. For the other two patients with larger residual motion, 4–5 repainting were needed. Conclusion: We recommend evaluation of the 4DCT motion histogram following simulation and the interplay effect following treatment planning in order to personalize the use of compression and volumetric repainting for each patient. Abdominal compression enables safe and more effective PBS treatment of liver tumors by reduction of motion and interplay effect. Kevin Souris is supported by IBA and Televie Grant

Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

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Azadeh Nabizadeh Haghighi

2016-03-01

Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

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Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

Reduced Expression of the Liver/Beta-Cell Glucose Transporter Isoform in Glucose-Insensitive Pancreatic Beta Cells of Diabetic Rats

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Thorens, Bernard; Weir, Gordon C.; Leahy, John L.; Lodish, Harvey F.; Bonner-Weir, Susan

1990-09-01

Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor.

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS).

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Sheron, Nick; Moore, Michael; O'Brien, Wendy; Harris, Scott; Roderick, Paul

2013-10-01

In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals. To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption. A community feasibility study in nine general practice sites in Hampshire. Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis. In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, PAUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, PDetection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking.

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

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

2016-04-01

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

Acrolein scavengers, cysteamine and N-benzylhydroxylamine, reduces the mouse liver damage after acetaminophen overdose.

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Koyama, Ryo; Mizuta, Ryushin

2017-01-10

Our previous study suggested that the highly toxic α,β-unsaturated aldehyde acrolein, a byproduct of oxidative stress, plays a major role in acetaminophen-induced liver injury. In this study, to determine the involvement of acrolein in the liver injury and to identify novel therapeutic options for the liver damage, we examined two putative acrolein scavengers, a thiol compound cysteamine and a hydroxylamine N-benzylhydroxylamine, in cell culture and in mice. Our results showed that cysteamine and N-benzylhydroxylamine effectively prevented the cell toxicity of acrolein in vitro and acetaminophen-induced liver injury in vivo, which suggested that acrolein is involved in the liver damage, and these two drugs can be potential therapeutic options for this condition.

Distinct CCR2(+) Gr1(+) cells control growth of the Yersinia pestis ΔyopM mutant in liver and spleen during systemic plague.

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Ye, Zhan; Uittenbogaard, Annette M; Cohen, Donald A; Kaplan, Alan M; Ambati, Jayakrishna; Straley, Susan C

2011-02-01

We are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacterium Yersinia pestis. In this study, we pursued previous findings that Gr1(+) cells are required to selectively limit growth of ΔyopM Y. pestis and that CD11b(+) cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent Y. pestis. When PMNs were ablated from mice, ΔyopM Y. pestis grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to ΔyopM Y. pestis in both organs. In spleen, the Gr1(+) cells differentially recruited by parent and ΔyopM Y. pestis infections were CCR2(+) Gr1(+) CD11b(+) CD11c(Lo-Int) MAC3(+) iNOS(+) (inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the ΔyopM mutant was relieved by the parent Y. pestis strain in a coinfection assay in which the parent strain could affect the fate of the mutant in trans. In a mouse model of bubonic plague, CCR2 also was shown to be required for ΔyopM Y. pestis to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.

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

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Xiaolan Yang

2017-08-01

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

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

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

2017-01-01

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

Interactions of the heart and the liver

DEFF Research Database (Denmark)

Møller, Søren; Bernardi, Mauro

2013-01-01

There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting...... the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should...... be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic...

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

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

2015-08-01

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

Effect of splenectomy on liver cirrhosis and related surgical issues

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KONG Degang

2016-12-01

Full Text Available Patients with liver fibrosis and cirrhosis experience certain changes in spleen morphology and function, and there is always a controversy over whether to perform splenectomy in patients with liver cirrhosis. As a surgical treatment of recurrent portal hypertension complicated by esophagogastric variceal bleeding, splenectomy can reduce portal venous pressure, reduce the possibility of gastrointestinal bleeding, and correct the reduced white blood cell count and platelet count. It can also protect the liver by improving liver function, promoting regeneration of hepatocytes, and inhibiting the progression of liver fibrosis. With reference to available clinical and laboratory data, this article reviews the effect of splenectomy on the cirrhotic liver and related issues such as selection of surgical procedures and prevention and treatment of postoperative complications, in order to promote splenectomy in patients with liver cirrhosis.

High-frequency TRNS reduces BOLD activity during visuomotor learning.

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Catarina Saiote

Full Text Available Transcranial direct current stimulation (tDCS and transcranial random noise stimulation (tRNS consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI. We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1-100 Hz; hf-tRNS 101-640 Hz, respectively and sham stimulation over the primary motor cortex (M1 during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods.

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.

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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.

Ethanol extract of Portulaca Oleracea L. reduced the carbon tetrachloride induced liver injury in mice involving enhancement of NF-κB activity

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Shi, Hongguang; Liu, Xuefeng; Tang, Gusheng; Liu, Haiyan; Zhang, Yinghui; Zhang, Bo; Zhao, Xuezhi; Wang, Wanyin

2014-01-01

Acute hepatic injury causes high morbidity and mortality world-wide. Management of severe acute hepatic failure continues to be one of the most challenging problems in clinical medicine. In present study, carbon tetrachloride (CCl4) was used to induce acute liver damage in mice and the protective effects of ethanol extract of Portulaca Oleracea L. (PO) were examined. The aminotransferase activities were biochemical estimated and the liver damage was tested by morphological histological analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The role of PO on the activity of NF-κB was determined by luciferase reporter gene assay and immunohistochemistry. The level of p-p65 was tested by western blot. Our results showed that PO administration on mice would decrease the serum aminotransferase level and reduced the liver histological damage. We also found that nuclear translocation of p65 was enhanced in liver tissues of mice treated with PO compared with control animals. In addition, in cultured hepatic cells, PO increased the NF-κB luciferase reporter gene activity and upregulated the level of phosphorylation of p65, but had no effects on mice liver SOD activity and MDA level. Collectively, PO attenuated CCl4 induced mice liver damage by enhancement of NF-κB activity. PMID:25628785

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

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Gevers Tom JG

2012-04-01

Full Text Available Abstract Background A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD. The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. Methods/design This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, α1-microglobulin, KIM-1, H-FABP, MCP-1 and serum (fibroblast growth factor 23 biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. Discussion We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. Trial registration number Clinical trials.gov NCT01354405

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

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Beat Meier

2018-06-01

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

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

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Mahboube Ebadi

2017-08-01

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

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

Energy Technology Data Exchange (ETDEWEB)

Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

2014-07-25

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

International Nuclear Information System (INIS)

Prasad, Vikram; Chirra, Shivani; Kohli, Rohit; Shull, Gary E.

2014-01-01

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na + /H + exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-07-01

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

Endocrine-Manifestations of Cirrhosis and Liver Disease

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M Khalili

2014-04-01

Full Text Available The liver is involved in the synthesis and metabolism of many kinds of hormones, various abnormalities hormone levels are found in advanced liver disease. For example the liver is, extremely sensitive to changes in insulin or glucagon levels. The liver is the primary organ of iron storage is frequently involved, diabetes is common in patients with iron overload and may be seen in cirrhosis. Chronic infection with HCV is associated with insulin resistance. Thyroid disease often accompanies chronic hepatitis C infection .Anti thyroid autoantibodies are also found in chronic HCV infection. Nonalcoholic liver disease (NAFLDas a most common cause of chronic liver disease in western world ,as well accompanied by Type 2 diabetes and hyperlipidemia. Hypopituitarism and hypothyroidism also have been in NAFLD.The patients with NAFLD and Hypopituitarism may be susceptible to central obesity, dyslipidemia and insulin resistance leading to disease progression. Hepatic cirrhosis as the end stage of chronic liver disease is also associated with hypogonadism and signs of feminization. The peripheral metabolism of steroids is altered in many of hypogonadism, low testosterone level decreased libido, infertility, reduced secondary sex hair and gynecomastia, reduced spermatogenesis and peritubular fibrosis are found in men with cirrhosis .The normal function of the hypothalamic-pituitary gonadal axis is affected in liver disease. In cirrhotic patients the estrogen/androgen ratio is usually increased, the level of testosterone and dihydroepiandosteron are reduced while the estradiol level are normal or slightly elevated, these alterations are dependent on the severity of the liver disease.Succsesfull orthotropic liver transplantation  leads to improvement of the sex hormone disturbances. The pathogenesis of gynecomastia is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state but it is due to increased estrogen precursor in

Role of α-Dicarbonyl Compounds in the Inhibition Effect of Reducing Sugars on the Formation of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Science.gov (United States)

Han, Zhonghui; Liu, Bing; Niu, Zhiyan; Zhang, Yan; Gao, Jianxin; Shi, Lei; Wang, Shujun; Wang, Shuo

2017-11-22

The effect of reducing sugars on formation of PhIP in fried pork was investigated, and the underlying mechanisms were revealed by studying the reaction pathways between α-dicarbonyl compounds (α-DCs) and PhIP. The addition of reducing sugars (such as glucose) greatly reduced the amount of PhIP in fried pork from 15.5 ng/g to less than 1.0 ng/g. The amount of PhIP decreased significantly with an increasing level of added α-DCs in model systems. Similarly, the addition of methylglyoxal (MGO) decreased significantly the levels of phenylalanine (Phe) and creatinine (Crn) but increased significantly the level of phenylacetaldehyde (PEA). 2-Amino-1-methyl-5-(2-oxopropylidene)-imidazol-4-one and N-(1-methyl-4-oxoimidazolidin-2-ylidene) amino propionic acids were identified in MGO/Crn and MGO/Crn/Phe model systems and fried pork with glucose. These results revealed that the degradation products of reducing sugars-α-DCs-play an important role in inhibiting formation of PhIP by reacting with key precursors of PhIP and itself.

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

Science.gov (United States)

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

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

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo.

Science.gov (United States)

Chuang, Cheng-Hung; Tsai, Cheng-Chih; Lin, En-Shyh; Huang, Chin-Shiu; Lin, Yun-Yu; Lan, Chuan-Ching; Huang, Chun-Chih

2016-10-31

The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo

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Cheng-Hung Chuang

2016-10-01

Full Text Available The aim of the present study was to determine whether Lactobacillus salivarius (LS and Lactobacillus johnsonii (LJ prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST, alanine transaminase (ALT, gamma-glutamyl transferase (γ-GT, lipid peroxidation, triglyceride (TG and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

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

Science.gov (United States)

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.

Chronic alcohol binging injures the liver and other organs by reducing NAD⁺ levels required for sirtuin's deacetylase activity.

Science.gov (United States)

French, Samuel W

2016-04-01

NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de-acetylate acetylated proteins such as acetylated histones. This prevents the epigenetic changes that regulate metabolic processes and which prevent organ injury such as fatty liver in response to alcohol abuse. Hyper acetylation of numerous regulatory proteins develops. Systemic multi-organ injury occurs when NAD(+) is reduced. For instance the Circadian clock is altered if NAD(+) is not available. Cell cycle arrest occurs due to up regulation of cell cycle inhibitors leading to DNA damage, mutations, apoptosis and tumorigenesis. NAD(+) is linked to aging in the regulation of telomere stability. NAD(+) is required for mitochondrial renewal. Alcohol dehydrogenase is present in every visceral organ in the body so that there is a systemic reduction of NAD(+) levels in all of these organs during binge drinking. Copyright © 2016. Published by Elsevier Inc.

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

Science.gov (United States)

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

2015-01-01

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

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

Science.gov (United States)

Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

2017-11-01

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

Age dependence of rat liver function measurements

DEFF Research Database (Denmark)

Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

1989-01-01

Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

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

Science.gov (United States)

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

2013-11-15

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

The HLT, DAQ and DCS TDR

CERN Multimedia

Wickens, F. J

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

Interfraction Liver Shape Variability and Impact on GTV Position During Liver Stereotactic Radiotherapy Using Abdominal Compression

International Nuclear Information System (INIS)

Eccles, Cynthia L.; Dawson, Laura A.; Moseley, Joanne L.; Brock, Kristy K.

2011-01-01

Purpose: For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. Methods and Materials: Evaluable patients were treated in a Research Ethics Board-approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCT scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house-developed finite-element model-based deformable registration (MORFEUS). Results: We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left-right (LR), anterior-posterior (AP), and superior-inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left-right, anterior-posterior, and superior-inferior directions, respectively. Conclusions: Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid liver-to-liver

The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

Science.gov (United States)

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

Coffee: The magical bean for liver diseases

OpenAIRE

Heath, Ryan D; Brahmbhatt, Mihir; Tahan, Asli C; Ibdah, Jamal A; Tahan, Veysel

2017-01-01

Coffee has long been recognized as having hepatoprotective properties, however, the extent of any beneficial effect is still being elucidated. Coffee appears to reduce risk of hepatocellular carcinoma, reduce advancement of fibrotic disease in a variety of chronic liver diseases, and perhaps reduce ability of hepatitis C virus to replicate. This review aims to catalog the evidence for coffee as universally beneficial across a spectrum of chronic liver diseases, as well as spotlight opportunit...

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

Directory of Open Access Journals (Sweden)

Ryo Ishibashi

2018-01-01

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

CT of liver steatosis after subtotal pancreatectomy

Energy Technology Data Exchange (ETDEWEB)

Lundstedt, C.; Andren-Sandberg, A. (Lund Univ. (Sweden). Dept. of Diagnostic Radiology Lund Univ. (Sweden). Dept. of Surgery)

1991-01-01

The liver attenuation of 50 patients operated with a subtotal pancreatectomy for pancreatic and duodenal tumors was evaluated with CT. Of 18 patients surviving more than 18 months after surgery, 7 developed a markedly reduced liver attenuation indicating liver steatosis. No patient became diabetic or showed evidence of malnutrition after surgery. No correlation between the liver attenuation values and the patients' liver function test was noted. The steatosis was reversible in 4 of the 7 patients. The pathophysiological cause of the steatosis remains unknown. Partial pancreatectomy should be included among the reasons listed for liver steatosis. (orig.).

CT of liver steatosis after subtotal pancreatectomy

International Nuclear Information System (INIS)

Lundstedt, C.; Andren-Sandberg, A.; Lund Univ.

1991-01-01

The liver attenuation of 50 patients operated with a subtotal pancreatectomy for pancreatic and duodenal tumors was evaluated with CT. Of 18 patients surviving more than 18 months after surgery, 7 developed a markedly reduced liver attenuation indicating liver steatosis. No patient became diabetic or showed evidence of malnutrition after surgery. No correlation between the liver attenuation values and the patients' liver function test was noted. The steatosis was reversible in 4 of the 7 patients. The pathophysiological cause of the steatosis remains unknown. Partial pancreatectomy should be included among the reasons listed for liver steatosis. (orig.)

CT of liver steatosis after subtotal pancreatectomy

Energy Technology Data Exchange (ETDEWEB)

Lundstedt, C; Andren-Sandberg, A [Lund Univ. (Sweden). Dept. of Diagnostic Radiology Lund Univ. (Sweden). Dept. of Surgery

1991-01-01

The liver attenuation of 50 patients operated with a subtotal pancreatectomy for pancreatic and duodenal tumors was evaluated with CT. Of 18 patients surviving more than 18 months after surgery, 7 developed a markedly reduced liver attenuation indicating liver steatosis. No patient became diabetic or showed evidence of malnutrition after surgery. No correlation between the liver attenuation values and the patients' liver function test was noted. The steatosis was reversible in 4 of the 7 patients. The pathophysiological cause of the steatosis remains unknown. Partial pancreatectomy should be included among the reasons listed for liver steatosis. (orig.).

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

NARCIS (Netherlands)

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

2015-01-01

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

Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury.

Science.gov (United States)

Jiao, Shu-Fan; Sun, Kai; Chen, Xiao-Jing; Zhao, Xue; Cai, Ning; Liu, Yan-Jun; Xu, Long-Mei; Kong, Xian-Ming; Wei, Li-Xin

2014-01-08

Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection. Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors. These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.

Standardisation of liver MDCT by tracking liver parenchyma enhancement to trigger imaging

International Nuclear Information System (INIS)

Brodoefel, H.; Tognolini, A.; Zamboni, G.A.; Gourtsoyianni, S.; Raptopoulos, V.; Claussen, C.D.

2012-01-01

To assess parenchymal bolus-triggering in terms of liver enhancement, lesion-to-liver conspicuity and inter-image variability across serial follow-up MDCTs. We reviewed MDCTs of 50 patients with hepatic metastases who had a baseline CT and two follow-up examinations. In 25 consecutive patients CT data acquisition was initiated by liver parenchyma triggering at a 50-HU enhancement threshold. In a matched control group, imaging was performed with an empirical delay of 65 s. CT attenuation values were assessed in vessels, liver parenchyma and metastasis. Target lesions were classified according to five enhancement patterns. Compared with the control group, liver enhancement was significantly higher with parenchyma triggering (59.8 ± 7.6 HU vs. 48.8 ± 11.2 HU, P = 0.0002). The same was true for conspicuity (liver parenchyma - lesion attenuation) of hypo-enhancing lesions (72.2 ± 15.9 HU vs. 52.7 ± 19.4 HU, P = 0.0006). Liver triggering was associated with reduced variability for liver enhancement among different patients (P = 0.035) and across serial follow-up examinations in individual patients (P < 0.0001). The number of patients presenting with uniform lesion enhancement pattern across serial examinations was significantly higher in the triggered group (20 vs. 11; P = 0.018). Liver parenchyma triggering provides superior lesion conspicuity and improves standardisation of image quality across follow-up examinations with greater uniformity of enhancement patterns. (orig.)

Inhibition of Cyclic Adenosine Monophosphate (cAMP-response Element-binding Protein (CREB-binding Protein (CBP/β-Catenin Reduces Liver Fibrosis in Mice

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Yosuke Osawa

2015-11-01

Full Text Available Wnt/β-catenin is involved in every aspect of embryonic development and in the pathogenesis of many human diseases, and is also implicated in organ fibrosis. However, the role of β-catenin-mediated signaling on liver fibrosis remains unclear. To explore this issue, the effects of PRI-724, a selective inhibitor of the cAMP-response element-binding protein-binding protein (CBP/β-catenin interaction, on liver fibrosis were examined using carbon tetrachloride (CCl4- or bile duct ligation (BDL-induced mouse liver fibrosis models. Following repetitive CCl4 administrations, the nuclear translocation of β-catenin was observed only in the non-parenchymal cells in the liver. PRI-724 treatment reduced the fibrosis induced by CCl4 or BDL. C-82, an active form of PRI-724, inhibited the activation of isolated primary mouse quiescent hepatic stellate cells (HSCs and promoted cell death in culture-activated HSCs. During the fibrosis resolution period, an increase in F4/80+ CD11b+ and Ly6Clow CD11b+ macrophages was induced by CCl4 and was sustained for two weeks thereafter, even after having stopped CCl4 treatment. PRI-724 accelerated the resolution of CCl4-induced liver fibrosis, and this was accompanied by increased matrix metalloproteinase (MMP-9, MMP-2, and MMP-8 expression in intrahepatic leukocytes. In conclusion, targeting the CBP/β-catenin interaction may become a new therapeutic strategy in treating liver fibrosis.

Pre-existing liver cirrhosis reduced the toxic effect of diethylene glycol in a rat model due to the impaired hepatic alcohol dehydrogenase.

Science.gov (United States)

Ming Xing Huang; Xiao Mou Peng; Lin Gu; Gui Hua Chen

2011-09-01

Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were intraperitoneally administered a single dose of DEG, and randomly killed 1, 2, 5 or 8 days following exposure. Compared with control rats, the model rats had significantly higher blood CO(2)-combining power, lower blood urine nitrogen, serum creatinine and alanine aminotransferase levels on the second day and a lower mortality rate on the eighth day following DEG exposure. Enlargements of liver and kidneys and degeneration and necrosis of hepatocytes and renal tubules in the model rats was also less serious than in the control rats. Urine DEG levels were significantly higher on the first day in the model rats than the control rats (46.65 ± 8.79 mg vs 18.88 ± 6.18 mg, p activity in the model rats was significantly lower than that in the control rats, which was positively related to renal damage. The toxic effects of DEG in rats with pre-existing liver cirrhosis are significantly reduced, which may be due to the decreased hepatic ADH activity. It suggests that the metabolite of ADH is responsible for DEG poisoning, and this toxic metabolite may mainly originate in the liver.

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

Science.gov (United States)

Chen, W-Y; Lee, C-Y; Lin, P-Y; Hsieh, C-E; Ko, C-J; Lin, K-H; Lin, C-C; Ming, Y-Z; Chen, Y-L

2017-03-01

Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts. Copyright © 2016 Elsevier Inc. All rights reserved.

Cavitation enhances coagulated size during pulsed high-intensity focussed ultrasound ablation in an isolated liver perfusion system.

Science.gov (United States)

Zhao, Lu-Yan; Liu, Shan; Chen, Zong-Gui; Zou, Jian-Zhong; Wu, Feng

2016-11-24

To investigate whether cavitation enhances the degree of coagulation during pulsed high-intensity focussed ultrasound (HIFU) in an isolated liver perfusion system. Isolated liver was treated by pulsed HIFU or continuous-wave HIFU with different portal vein flow rates. The cavitation emission during exposure was recorded, and real-time ultrasound images were used to observe changes in the grey scale. The coagulation size was measured and calculated. HIFU treatment led to complete coagulation necrosis and total cell destruction in the target regions. Compared to exposure at a duty cycle (DC) of 100%, the mean volumes of lesions induced by 6 s exposure at DCs of 50% and 10% were significantly larger (P cavitation activity for the pulsed-HIFU (P > .05). For continuous-wave HIFU exposure, there was a significant decrease in the necrosis volume and cavitation activity for exposure times of 1, 2, 3, 4, and 6 s with increasing portal perfusion rates. Perfusion flow rates negatively influence cavitation activity and coagulation volume. Ablation is significantly enhanced during pulsed HIFU exposure compared with continuous-wave HIFU.

Effect of perches on liver health of hens.

Science.gov (United States)

Jiang, S; Hester, P Y; Hu, J Y; Yan, F F; Dennis, R L; Cheng, H W

2014-07-01

Fatty liver is a common energy metabolic disorder in caged laying hens. Considering that the egg industry is shifting from conventional cages to alternative housing systems such as enriched cages, the objective of this study was to determine the effects of perches on fat deposition and liver health in laying hens. Three hundred twenty-four 17-wk-old White Leghorn hens were housed in 1 of 4 treatments with 9 hens per cage. Treatment 1 hens never had access to perches during their life cycle. Treatment 2 hens had access to perches during the pullet phase only. Treatment 3 hens had access to perches during the laying phase only. Treatment 4 hens always had access to perches. Liver weight, abdominal fat pad weight, BW, liver fat, and circulating alanine transaminase, aspartate transaminase, and adiponectin were determined. Provision of perches during either the rearing or laying phase did not affect liver health in 71-wk-old hens. However, perch access compared with no perch access during the egg laying phase reduced relative fat pad weight. These results suggest that providing perches as a means of stimulating activity reduced abdominal fat deposition in caged hens during the laying period. However, perch access in caged hens was ineffective in reducing fat deposition in the liver and altering enzyme activities related to improved liver function. © 2014 Poultry Science Association Inc.

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

Science.gov (United States)

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

2016-03-15

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

Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

DEFF Research Database (Denmark)

Khamri, Wafa; Abeles, Robin D; Hou, Tie Zheng

2017-01-01

, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood...... mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF......BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86...

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice.

Science.gov (United States)

Lohr, Kerstin; Pachl, Fiona; Moghaddas Gholami, Amin; Geillinger, Kerstin E; Daniel, Hannelore; Kuster, Bernhard; Klingenspor, Martin

2016-10-01

Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle-aged mice. Susceptibility to diet-induced obesity increased with age. Young adult and middle-aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age-related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet-induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie

2016-04-21

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

2016-01-01

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

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

Science.gov (United States)

Wexler, Anna

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

Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C

Directory of Open Access Journals (Sweden)

Tseng CW

2016-03-01

difference in 3-year cumulative incidence of liver cirrhosis was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0–57.5, P=0.012 compared with those with SVR (10.4%, 95% CI: 3.1–17.7. There was a trend of a higher baseline aspartate aminotransferase-to-platelet ratio index score in patients who progressed to liver cirrhosis compared with those who did not progress (2.1±1.2 vs 1.6±1.3, P=0.055, but the difference failed to reach significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921–1.791, P=0.14. Conclusion: An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients. Keywords: hepatitis C, sustained virologic response, pegylated interferon, ribavirin, liver cirrhosis

PPAR-gamma activation is associated with reduced liver ischemia-reperfusion injury and altered tissue-resident macrophages polarization in a mouse model.

Science.gov (United States)

Linares, Ivan; Farrokhi, Kaveh; Echeverri, Juan; Kaths, Johan Moritz; Kollmann, Dagmar; Hamar, Matyas; Urbanellis, Peter; Ganesh, Sujani; Adeyi, Oyedele A; Yip, Paul; Selzner, Markus; Selzner, Nazia

2018-01-01

PPAR-gamma (γ) is highly expressed in macrophages and its activation affects their polarization. The effect of PPAR-γ activation on Kupffer cells (KCs) and liver ischemia-reperfusion injury (IRI) has not yet been evaluated. We investigated the effect of PPAR-γ activation on KC-polarization and IRI. Seventy percent (70%) liver ischemia was induced for 60mins. PPAR-γ-agonist or vehicle was administrated before reperfusion. PPAR-γ-antagonist was used to block PPAR-γ activation. Liver injury, necrosis, and apoptosis were assessed post-reperfusion. Flow-cytometry determined KC-phenotypes (pro-inflammatory Nitric Oxide +, anti-inflammatory CD206+ and anti-inflammatory IL-10+). Liver injury assessed by serum AST was significantly decreased in PPAR-γ-agonist versus control group at all time points post reperfusion (1hr: 3092±105 vs 4469±551; p = 0.042; 6hr: 7041±1160 vs 12193±1143; p = 0.015; 12hr: 5746±328 vs 8608±1259; p = 0.049). Furthermore, liver apoptosis measured by TUNEL-staining was significantly reduced in PPAR-γ-agonist versus control group post reperfusion (1hr:2.46±0.49 vs 6.90±0.85%;p = 0.001; 6hr:26.40±2.93 vs 50.13±8.29%; p = 0.048). H&E staining demonstrated less necrosis in PPAR-γ-agonist versus control group (24hr:26.66±4.78 vs 45.62±4.57%; p = 0.032). The percentage of pro-inflammatory NO+ KCs was significantly lower at all post reperfusion time points in the PPAR-γ-agonist versus control group (1hr:28.49±4.99 vs 53.54±9.15%; p = 0.040; 6hr:5.51±0.54 vs 31.12±9.58%; p = 0.009; 24hr:4.15±1.50 vs 17.10±4.77%; p = 0.043). In contrast, percentage of anti-inflammatory CD206+ KCs was significantly higher in PPAR-γ-agonist versus control group prior to IRI (8.62±0.96 vs 4.88 ±0.50%; p = 0.04). Administration of PPAR-γ-antagonist reversed the beneficial effects on AST, apoptosis, and pro-inflammatory NO+ KCs. PPAR-γ activation reduces IRI and decreases the pro-inflammatory NO+ Kupffer cells. PPAR-γ activation can become an

Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report

Directory of Open Access Journals (Sweden)

Toyama Yoichi

2012-06-01

Full Text Available Abstract A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

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Oliveira C.P.M.S.

2006-01-01

Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

Effect of selective hepatic inflow occlusion during liver cancer resection on liver ischemia-reperfusion injury

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Yin-Tian Deng

2016-11-01

Full Text Available Objective: To study the effect of selective hepatic inflow occlusion during liver cancer resection on liver ischemia-reperfusion injury. Methods: A total of 68 patients with primary liver cancer who underwent left liver resection in our hospital between May 2012 and August 2015 were selected for study and divided into group A (selective hepatic inflow occlusion of left liver and group B (Prignle hepatic inflow occlusion according to different intraoperative blood occlusion methods, serum was collected before and after operation to determine liver enzyme content, the removed liver tissue was collected to determine energy metabolism indexes, inflammation indexes and oxidative stress indexes. Results: 1 d, 3 d and 5 d after operation, GPT, GOT, GGT, LDH and ALP content in serum of both groups were significantly higher than those before operation, and GPT, GOT, GGT, LDH and ALP content in serum of group A 1 d, 3 d and 5 d after operation were significantly lower than those of group B; ATP, ADP, AMP, PI3K, AKT, GSK3β, T-AOC, PrxI and Trx content in liver tissue of group A were significantly higher than those of group B while PTEN, IL-12p40, MDA and MPO content were significantly lower than those of group B. Conclusions: Selective hepatic inflow occlusion during liver cancer resection can reduce the liver ischemia-reperfusion injury, improve the energy metabolism of liver cells and inhibit inflammation and oxidative stress in liver tissue.

Left prefrontal neuronavigated electrode localization in tDCS : 10–20 EEG system versus MRI-guided neuronavigation

NARCIS (Netherlands)

De Witte, Sara; Klooster, Debby; Dedoncker, Josefien; Duprat, Romain; Remue, Jonathan; Baeken, Chris

2018-01-01

Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral

Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

DEFF Research Database (Denmark)

Gravholt, Claus Højbjerg; Poulsen, H.E.; Ott, Peter

2007-01-01

Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

International Nuclear Information System (INIS)

Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael

2015-01-01

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

Science.gov (United States)

Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

2015-04-01

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

Energy Technology Data Exchange (ETDEWEB)

Roversi, Katiane, E-mail: katianeroversi@gmail.com [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Benvegnú, Dalila M., E-mail: dalilabenvegnu@yahoo.com.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Roversi, Karine, E-mail: karineroversi-@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Trevizol, Fabíola, E-mail: fatrevizol@yahoo.com.br [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Vey, Luciana T., E-mail: luciana.taschetto@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Elias, Fabiana, E-mail: fabiana.elias@uffs.edu.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Fracasso, Rafael, E-mail: rafael.fra@hotmail.com [Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Farmacêuticas (Brazil); and others

2015-04-15

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

Liver Transplantation for Unresectable Metastases from Colon Adenocarcinoma

Directory of Open Access Journals (Sweden)

Luis Armando Caicedo

2017-01-01

Full Text Available Liver transplantation is an option that improves quality of life and prolongs life expectancy in patients with different types of liver disease. Liver transplantation is controversial for colorectal metastases and is not recommended in clinical practice guidelines. In this case report, we present, to our knowledge, the first liver transplantation for colorectal metastases conducted in Colombia, with a successful follow-up of more than 2 years. Patients with these characteristics who underwent liver transplantation experience reduced mortality and exponentially improved quality of life.

Liver cell-targeted delivery of therapeutic molecules.

Science.gov (United States)

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Markers of liver function and inflammatory cytokines modulation by ...

African Journals Online (AJOL)

Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

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.

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Manfred B. Lutz

2017-10-01

Full Text Available 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.

Iodine 123-17-iodoheptadecanoic acid for metabolic liver studies in humans

International Nuclear Information System (INIS)

Hoeck, A.S.; Spohr, G.; Schmitz, M.; Notohamiprodjo, G.; Porschen, R.; Vyska, K.; Freundlieb, C.; Shreeve, W.W.; Feinendegen, L.E.

1986-01-01

(17- 123 I)-Iodoheptadecanoic acid ([ 123 I]HA) was used for dynamic planar scintigraphy of the liver in normal individuals (control I), in patients without liver disease but with elevated serum cholesterol and/or triglycerides (control II), and in patient groups with alcohol-induced fatty liver (PG I), fatty liver not due to alcohol (PG II), alcohol-induced liver cirrhosis (PG III), or liver cirrhosis of the posthepatitic type (PG IV). Tracer uptake and elimination time were assayed in different liver regions; mean elimination time was expressed for total liver. In control I, tracer uptake was homogeneous, and mean elimination time was 20.7 +/- 5.3 min without significant local variations. In control II, tracer uptake was reduced but homogeneous and mean elimination time was 59.4 +/- 35.8 min with some local variations. In PG I, uptake was reduced and inhomogeneous and elimination time was the same as in control I, irrespective of cholesterol and triglyceride values. In PG II, uptake was the same as in PG I but mean elimination time was 48 +/- 8.1 min with some local variations. In PG III, uptake was extremely reduced and spotty and elimination time correlated with the severity of disease from 19 to 881 min in different liver regions

EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

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Nádia Araújo Miguel

2016-07-01

Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

Effect of 6-Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function

Science.gov (United States)

Larson-Meyer, D. Enette; Newcomer, Bradley R.; Heilbronn, Leonie K.; Volaufova, Julia; Smith, Steven R.; Alfonso, Anthony J.; Lefevre, Michael; Rood, Jennifer C.; Williamson, Donald A.; Ravussin, Eric

2009-01-01

objective Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low-calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results At baseline, increased liver lipid content (by MRS) correlated (P triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD. PMID:18421281

Flow, Liver, Flow: A Retrospective Analysis of the Interplay of Liver Disease and Coagulopathy in Chronic Subdural Hematoma.

Science.gov (United States)

Kolcun, John Paul George; Gernsback, Joanna Elizabeth; Richardson, Angela Mae; Jagid, Jonathan Russell

2017-06-01

Chronic subdural hematoma (cSDH) is a common neurosurgical ailment, particularly in elderly patients. A recent study uncovered an association between liver disease and recurrence in patients with cSDH. Here, we explored that relationship to identify recurrence predictors in at-risk patients. We hypothesized that the association between liver disease and recurrence was attributable to coagulopathy secondary to liver disease. We retrospectively reviewed all patients with cSDH treated with burr-hole drainage by 2 surgeons between 2007 and 2015. Comorbidities and laboratory findings for each patient were examined by Pearson χ 2 analysis or Mann-Whitney U tests. We identified 261 cSDH in 215 patients. Patients were a mean age of 65.6 years, and 72% were male. Sixteen patients with cSDH required repeat surgery (6.1%). There were 123 coagulopathic patients (47.1%), and 14 with liver disease (5.4%), all of whom were coagulopathic (P < 0.001). Coagulopathic patients with liver disease were more likely to experience recurrence than patients with coagulopathy alone (relative risk = 4.09, P = 0.019). Patients with liver disease had significantly elevated prothrombin time (P = 0.013) and reduced platelet counts (P < 0.001). Platelets also were reduced in coagulopathic patients with liver disease, as compared with those with coagulopathy alone (P = 0.002). Thrombocytopenia remained significant in a multivariate analysis (P < 0.001). Liver disease is significantly associated with the recurrence of cSDH. Although coagulopathy alone does not predict recurrence, patients with coagulopathy and liver disease are at greater risk for recurrence than those with coagulopathy alone. Liver disease effects are reflected in certain hematologic laboratory values. Copyright © 2017 Elsevier Inc. All rights reserved.

Idiopathic extensive peliosis hepatis treated with liver transplantation

DEFF Research Database (Denmark)

Hyodo, Masanobu; Mogensen, Anne Mellon; Larsen, Peter Nørgaard

2004-01-01

A 50-year-old Danish man, who neither had wasting disease nor was taking steroid-containing drugs, complained of abdominal distension, due to a markedly enlarged liver. Percutaneous needle biopsies were taken from the liver, and the findings gave suspicion of a neoplastic tumor. Because of reduced...... liver function and treatment-resistant ascites, he underwent liver transplantation without a definite preoperative diagnosis. The resected liver weighed 2900 g, and almost all of the parenchyma was destroyed and replaced by multicystic blood-filled spaces, diagnosed as extensive peliosis hepatis...

Pediatric liver transplantation in 31 consecutive children

Institute of Scientific and Technical Information of China (English)

SHEN Zhong-yang; WANG Zi-fa; ZHU Zhi-jun; ZANG Yun-jin; ZHENG Hong; DENG Yong-lin; PAN Cheng; CHEN Xin-guo

2008-01-01

Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children (≤18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher

Beta band transcranial alternating (tACS and direct current stimulation (tDCS applied after initial learning facilitate retrieval of a motor sequence

Directory of Open Access Journals (Sweden)

Vanessa eKrause

2016-01-01

Full Text Available The primary motor cortex (M1 contributes to the acquisition and early consolidation of a motor sequence. Although the relevance of M1 excitability for motor learning has been supported, the significance of M1 oscillations remains an open issue. This study aims at investigating to what extent retrieval of a newly learned motor sequence can be differentially affected by motor-cortical transcranial alternating (tACS and direct current stimulation (tDCS. Alpha (10 Hz, beta (20 Hz or sham tACS was applied in 36 right-handers. Anodal or cathodal tDCS was applied in 30 right-handers. Participants learned an eight-digit serial reaction time task (SRTT; sequential vs. random with the right hand. Stimulation was applied to the left M1 after SRTT acquisition at rest for ten minutes. Reaction times were analyzed at baseline, end of acquisition, retrieval immediately after stimulation and reacquisition after eight further sequence repetitions.Reaction times during retrieval were significantly faster following 20 Hz tACS as compared to 10 Hz and sham tACS indicating a facilitation of early consolidation. TDCS yielded faster reaction times, too, independent of polarity. No significant differences between 20 Hz tACS and tDCS effects on retrieval were found suggesting that 20 Hz effects might be associated with altered motor-cortical excitability. Based on the behavioural modulation yielded by tACS and tDCS one might speculate that altered motor-cortical beta oscillations support early motor consolidation possibly associated with neuroplastic reorganization.

Effect of transcranial direct current stimulation (tDCS) over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial

OpenAIRE

Shiozawa, Pedro; Gomes, July Silveira; Ducos, Daniella Valverde; Akiba, Henrique Teruo; Dias, Álvaro Machado; Trevizol, Alisson Paulino; Uchida, Ricardo R.; Orlov, Natasza; Cordeiro, Quirino

2016-01-01

Abstract Introduction: We report a transcranial direct current stimulation (tDCS) protocol over the dorsolateral prefrontal cortex (DLPFC) combined with cognitive training in schizophrenia. Method: We assessed psychotic symptoms in nine patients using the Positive and Negative Syndrome Scale (PANSS). All evaluations were scored at baseline, at the end of the intervention protocol, and during a 4-week follow-up. The tDCS protocol consisted of 10 consecutive sessions over 5-day periods. We pl...

Coffee and liver health.

Science.gov (United States)

Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

2014-01-01

Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

The Role of Butylidenephthalide in Targeting Microenvironment Contributes to the Ameliorate of Liver Fibrosis

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Hong-Meng eChuang

2016-04-01

Full Text Available The treatment of liver fibrosis has clinical limitations because of its multiple etiologies, such as epithelial–mesenchymal transition (EMT promotion, cell regeneration and remodeling dysfunction, inflammatory cell activation, and scar tissue deposition. These factors might be considered as a new target for the fibrotic microenvironment, leading to increased fibrogenesis and liver fibrosis. Here, we investigate a small molecule named butylidenephthalide (BP and its multiple effects on liver fibrosis treatment. Thioacetamide was used in vivo to induce chronic liver fibrosis. BP was administered orally in rats for a period of 2 weeks and 4 weeks, which resulted in a significantly reduced fibrosis score (p<0.05 and (p<0.001, respectively. The inflammatory reaction of macrophage infiltration were reduced in the administration of BP, which led to the decrease in the transaminase levels. Moreover, we also found liver functions recovering (due to the increased serum albumin and reduced prothrombin time where liver cells regenerated, which can be seen in the increase of Ki-67 on Oval cell. In addition, the fibrotic scar was also reduced, along with the expression of matrix metalloprotease by hepatic stellate cell. Furthermore, regarding the mechanism/study of EMT reduced by BP, the knockdown of BMP-7, which could reduce α-SMA expression, was mediated by the regulation of TGF-β, which implies its major role on EMT. Finally, in the in vivo study, BP treatment of liver fibrosis was reduced by Bmp7 knockdown in zebrafish, suggesting that BP leads to the reduction of liver fibrosis, which also depends on BMP-7 induction. These results suggest that BP had multiple targets for treating liver fibrosis in the following ways: reduction of EMT, decreasing inflammatory reaction, and liver cell proliferation. This multiple targets approach provided a new mechanism to treat liver injury and fibrosis.

Enhancing verbal creativity: modulating creativity by altering the balance between right and left inferior frontal gyrus with tDCS.

Science.gov (United States)

Mayseless, N; Shamay-Tsoory, S G

2015-04-16

Creativity is the production of novel ideas that have value. Previous research indicated that while regions in the right hemisphere are implicated in the production of new ideas, damage to the left inferior frontal gyrus (IFG) is associated with increased creativity, indicating that the left IFG damage may have a "releasing" effect on creativity. To examine this, in the present study we used transcranial direct current stimulation (tDCS) to modulate activity of the right and the left IFG. In the first experiment we show that whereas anodal tDCS over the right IFG coupled with cathodal tDCS over the left IFG increases creativity as measured by a verbal divergent thinking task, the reverse stimulation does not affect creative production. To further confirm that only altering the balance between the two hemispheres is crucial in modulating creativity, in the second experiment we show that stimulation targeting separately the left IFG (cathodal stimulation) or the right IFG (anodal stimulation) did not result in changes in creativity as measured by verbal divergent thinking. These findings support the balance hypothesis, according to which verbal creativity requires a balance of activation between the right and the left frontal lobes, and more specifically, between the right and the left IFG. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Liver scintigraphy of fulminant hepatitis

International Nuclear Information System (INIS)

Tamaki, Nagara; Ishihara, Takashi; Mori, Toru

1980-01-01

The liver scintigraphies of five patients with fulminant hepatitis were examined. Scintiphotos using sup(99m)Tc-phytate were taken within two weeks after the onset. Scintiphotos of 12 normal subjects, 11 cases with acute hepatitis, 17 cases with liver cirrhosis were served as control. Their scintiphotos showed reduction of the size, well-maintained uptake, mostly homogenous RI distribution, and no left lobe enlargement, which could differentiate them from the chronic liver dysfunction. In one of the cases chronological changes in liver scintigraphy were observed. The size of the liver was reduced progressively until the 16th day and re-enlarged at the 30th day and thereafter. Three indices [S/W, (R + L)/W, and L/R] were calculated. S: area of liver, R or L: longitudinal length of the right or left lobe, W: body width. Relative size of the liver expressed by S/W or (R + L)/W showed significant reduction in fulminant hepatitis compared with acute hepatitis. However, they were not different significantly from those of normal subjects. Except for liver cirrhosis, L/R (left lobe swelling index) did not show significant differences among fulminant hepatitis, normal subjects, and acute hepatitis. These indices were also useful in follow-up study of the liver scintigraphy. The liver scintigraphy in the early phase of fulminant hepatitis seems to reflect the degree of massive hepatic necrosis. It is also useful to differentiate chronic hepatic failure. Apparant reduction in scintigraphical liver size seems to suggest poor prognosis, however, it should also kept in mind that the size of the liver in this condition might change quite rapidly and greatly. (author)

Thermoablation of Liver Metastases: Efficacy of Temporary Celiac Plexus Block

International Nuclear Information System (INIS)

Beck, A.N.; Schaefer, M.; Werk, M.; Pech, M.; Wieners, G.; Cho, C.; Ricke, J.

2005-01-01

Purpose. To determine the efficacy of celiac plexus block during thermoablation of liver metastases. Methods. Fifty-five consecutive patients underwent thermoablation therapy of liver tumors by laser-induced thermotherapy. Twenty-nine patients received a temporary celiac plexus block, 26 patients acted as control group. In both groups fentanyl and midazolam were administered intravenously upon request of the patient. The duration of the intervention, consumption of opiates, and individual pain sensations were documented. Results. No complications resulting from the celiac plexus block were recorded. Celiac plexus block significantly reduced the amount of pain medication used during thermoablation therapy of liver tumors (with block, 2.45 μg fentanyl per kg body weight; without block, 3.58 μg fentanyl per kg body weight, p < 0.05; midazolam consumption was not reduced) in patients with metastases ≤5 mm from the liver capsule. For metastases farther away from the capsule no significant differences in opiate consumption were seen. Celiac plexus block reduced the time for thermoablation significantly (178 min versus 147 min, p < 0.05) no matter how far the metastases were from the liver capsule. Average time needed to set the block was 12 min (range 9-15 min); additional costs for the block were marginal. As expected (as pain medications were given according to individual patients' needs) pain indices did not differ significantly between the two groups. Conclusion. In patients with liver metastases ≤5 mm from the liver capsule, celiac plexus block reduces the amount of opiates necessary, simplifying patient monitoring. In addition celiac plexus block reduces intervention time, with positive effects on overall workflow for all patients

Radiation-induced liver damage

International Nuclear Information System (INIS)

Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

1977-01-01

Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

Ventilatory strategy during liver transplantation

DEFF Research Database (Denmark)

Sørensen, Henrik; Grocott, Hilary P; Niemann, Mads

2014-01-01

BACKGROUND: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We investig......, this retrospective analysis suggests that attention to maintain a targeted EtCO2 would result in a more stable ScO2 during the operation....

Nutritional support of children with chronic liver disease