Long-Term Sickness Absence Due to Mental Disorders Is Associated with Individual Features and Psychosocial Work Conditions

PubMed Central

da Silva-Junior, João Silvestre; Fischer, Frida Marina

2014-01-01

Aims Sickness absence is a socioeconomic global burden. In Brazil, mental disorders are the third leading cause of social security benefits payments. The aim of the present study was to compare factors associated with long-term sickness absence between workers who claimed social benefits due to mental disorders or by other causes. We investigated individual features and occupational characteristics. In addition, we evaluated psychosocial factors at work assessed by the Demand-Control-Support (DCS) and Effort-Reward Imbalance (ERI) models, and whether they were associated with long-term sickness absence due to mental disorders (LTSA-MD). Methods The present case-control study was conducted in São Paulo, Brazil. The sample (n = 385) included workers on sick leave for more than 15 days. Cases were the participants with disabling psychiatric illnesses, and controls were the ones with other disabling diseases. Interviews were conducted to assess individual features (sociodemographic data, health habits/lifestyle, health conditions) and occupational characteristics. The participants' perception of exposure to dimensions of the DCS and ERI models was also recorded. Multiple logistic regressions were performed to evaluate the association between independent variables and LTSA-MD. Results All the regression analyses showed that LTSA-MD was associated with female sex, self-reported white skin color, higher education level, high tobacco consumption, high alcohol intake, two or more comorbidities, exposure to violence at work, high job strain and low social support at work, effort-reward imbalance and high overcommitment to work. LTSA-MD was associated with separate and combined DCS and ERI stress models. Conclusions Individual features and work conditions were associated with LTSA-MD. Combined analysis of stress models showed that psychosocial factors at work were significantly associated with LTSA-MD. Resourceful use of this information may contribute to the implementation of preventive actions and strategies to facilitate return to work targeting the populations most susceptible to mental disorders. PMID:25531900

Long-term sickness absence due to mental disorders is associated with individual features and psychosocial work conditions.

PubMed

Silva-Junior, João Silvestre da; Fischer, Frida Marina

2014-01-01

Sickness absence is a socioeconomic global burden. In Brazil, mental disorders are the third leading cause of social security benefits payments. The aim of the present study was to compare factors associated with long-term sickness absence between workers who claimed social benefits due to mental disorders or by other causes. We investigated individual features and occupational characteristics. In addition, we evaluated psychosocial factors at work assessed by the Demand-Control-Support (DCS) and Effort-Reward Imbalance (ERI) models, and whether they were associated with long-term sickness absence due to mental disorders (LTSA-MD). The present case-control study was conducted in São Paulo, Brazil. The sample (n = 385) included workers on sick leave for more than 15 days. Cases were the participants with disabling psychiatric illnesses, and controls were the ones with other disabling diseases. Interviews were conducted to assess individual features (sociodemographic data, health habits/lifestyle, health conditions) and occupational characteristics. The participants' perception of exposure to dimensions of the DCS and ERI models was also recorded. Multiple logistic regressions were performed to evaluate the association between independent variables and LTSA-MD. All the regression analyses showed that LTSA-MD was associated with female sex, self-reported white skin color, higher education level, high tobacco consumption, high alcohol intake, two or more comorbidities, exposure to violence at work, high job strain and low social support at work, effort-reward imbalance and high overcommitment to work. LTSA-MD was associated with separate and combined DCS and ERI stress models. Individual features and work conditions were associated with LTSA-MD. Combined analysis of stress models showed that psychosocial factors at work were significantly associated with LTSA-MD. Resourceful use of this information may contribute to the implementation of preventive actions and strategies to facilitate return to work targeting the populations most susceptible to mental disorders.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2011-06-15

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

Academic stress and active learning of nursing students: A cross-sectional study.

PubMed

Magnavita, Nicola; Chiorri, Carlo

2018-06-08

The active role of nursing students is particularly important in the delivery of health care, since playing an active role at the bedside and the use of active and collaborative engagement of students in the nursing activities has been associated with improved student learning. This is consistent with Karasek's learning hypothesis, but it has never been tested on nursing students. This study aimed at investigating whether nursing students in high control conditions reported lower levels of work impairment than students in the conditions with low control, compared them with a group of healthcare workers (HCWs), and tested the moderating role of social support at work. 633 nursing students and 160 HCWs completed the Nursing Work Functioning Questionnaire (NWFQ), and the Demand-Control-Support questionnaire (DCS). Results showed that nursing students reported higher levels of work impairment and were less likely to be classified as active (high demand/high control) or low strain (low demand/high control) than HCWs, and that social support at work moderated the association between being in active or low strain condition and work impairment. Programs to enhance the learning of nursing students must not only fight strain and isolation but must also promote active learning, by increasing the control over the job, team work, and support from teachers. Copyright © 2018. Published by Elsevier Ltd.

Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

PubMed

Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

2017-09-05

Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-05-04

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

Sex-specific interaction effects of age, occupational status, and workplace stress on psychiatric symptoms and allostatic load among healthy Montreal workers.

PubMed

Juster, Robert-Paul; Moskowitz, D S; Lavoie, Joel; D'Antono, Bianca

2013-11-01

Socio-demographics and workplace stress may affect men and women differently. The aim of this cross-sectional study was to assess sex-specific interactions among age, occupational status, and workplace Demand-Control-Support (D-C-S) factors in relation to psychiatric symptoms and allostatic load levels representing multi-systemic "wear and tear". It was hypothesized that beyond main effects, D-C-S factors would be moderated by occupational status and age in sex-specific directions predictive of subjective psychiatric symptoms and objective physiological dysregulations. Participants included healthy male (n = 81) and female (n = 118) Montreal workers aged 20 to 64 years (Men: M = 39.4 years, SD = 11.3; Women: M = 42.8 years, SD = 11.38). The Job Content Questionnaire was administered to assess workplace D-C-S factors that included psychological demands, decisional latitude, and social support. Occupational status was coded using the Nam--Powers--Boyd system derived from the Canadian census. Psychiatric symptoms were assessed using the Beck Anxiety Scale and the Beck Depression Inventory II. Sex-specific allostatic load indices were calculated based on fifteen biomarkers. Regression analyses revealed that higher social support was associated with less depressive symptoms in middle aged (p = 0.033) and older men (p = 0.027). Higher occupational status was associated with higher allostatic load levels for men (p = 0.035), while the reverse occurred for women (p = 0.048). Women with lower occupational status but with higher decision latitude had lower allostatic load levels, as did middle-aged (p = 0.031) and older women (p = 0.003) with higher psychological demands. In summary, age and occupational status moderated workplace stress in sex-specific ways that have occupational health implications.

Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia.

PubMed

Buttkus, Franziska; Baur, Volker; Jabusch, Hans-Christian; de la Cruz Gomez-Pellin, Maria; Paulus, Walter; Nitsche, Michael A; Altenmüller, Eckart

2011-01-01

Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument. Nine professional pianists suffering from MD were included in a placebo-controlled double-blinded study. Retraining consisted of slow, voluntarily controlled movements on the piano and was combined with tDCS. Patients were treated with three stimulation protocols: anodal tDCS, cathodal tDCS and placebo stimulation. No beneficial effects of single-session tDCS-supported sensorimotor retraining on fine motor control in pianists with MD were found in all three conditions. The main cause of the negative result of this study may be the short intervention time. One retraining session with a duration of 20 min seems not sufficient to improve symptoms of MD. Additionally, a single tDCS session might not be sufficient to modify sensorimotor learning of a highly skilled task in musicians with dystonia.

[Effect of occupational stress and effort-reward imbalance on sleep quality of people's policeman].

PubMed

Wu, Hui; Gu, Guizhen; Yu, Shanfa

2014-04-01

To explore the effect of occupational stress and effort-reward imbalance on sleep quality of people's police. A cluster sampling survey of sleep quality and occupational stress correlated factors was conducted on 287 police from a city public security bureau by questionnaires in May, 2011; the relationship between sleep quality and occupational stress correlated factors was analyzed by one-way ANOVA and multivariate non-conditional logistic regression using effort-reward imbalance model (ERI) and demand-control-support model (DCS). And the subjects were divided into high tension group and low tension group using the 1.0 of ERI and DCS coefficients as the boundary. The sleep quality score of shift work police was higher than day work police (11.95 ± 6.54 vs 9.52 ± 6.43, t = 2.77, P < 0.05).In ERI model, the sleep quality score in high tension group was higher than low tension group (14.50 ± 6.41 vs 8.60 ± 5.53, t = -5.32, P < 0.01), and in DCS model, the sleep quality score in high tension group was also higher than low tension group (13.71 ± 6.62 vs 9.46 ± 6.04, t = -3.71, P < 0.01).For the regression analysis of ERI model as an argument, sex (OR = 3.0, 95%CI:1.16-7.73) , age for 30-39 years (OR = 3.48, 95%CI:1.32-9.16) , intrinsic effort (OR = 2.30, 95%CI:1.10-4.81) and daily hassles (OR = 2.15, 95%CI:1.06-4.33) were risk factors of low sleep quality, and reward (OR = 0.26, 95%CI:0.12-0.52) was the protective factor.For the regression analysis of DCS model as an argument , age for 30-39 years (OR = 2.55, 95%CI:1.02-6.37) , depressive symptom (OR = 2.10, 95%CI:1.14-3.89) and daily hassles (OR = 3.25, 95%CI:1.70-6.19) were risk factors of low sleep quality.While the ERI model and the DCS model were analyzed simultaneously, sex (OR = 3.03, 95%CI:1.15-7.98) , age for 30-39 years (OR = 3.71, 95%CI:1.38-9.98) and daily hassles (OR = 2.09, 95%CI:1.01-4.30) were the risk factors of low sleep quality, and reward (OR = 0.22, 95%CI:0.10-0.48) was the protective factor. Occupational stress and effort-reward imbalance affected the sleep quality to people's policeman.

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

PubMed

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 events. Data collection was feasible and there were no missing data. Satisfaction with the tDCS-telehealth procedure was high and the patients were comfortable using the system. Conclusion: At-home tDCS with telehealth support appears to be a feasible approach for the management of symptom burden in patients with chronic illness. Further studies to evaluate and optimize the protocol effectiveness for symptom-control outcomes are warranted.

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

PubMed Central

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 events. Data collection was feasible and there were no missing data. Satisfaction with the tDCS-telehealth procedure was high and the patients were comfortable using the system. Conclusion: At-home tDCS with telehealth support appears to be a feasible approach for the management of symptom burden in patients with chronic illness. Further studies to evaluate and optimize the protocol effectiveness for symptom-control outcomes are warranted. PMID:29872381

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

PubMed

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.

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

PubMed

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

2016-01-01

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

Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation

PubMed Central

Obhi, Sukhvinder S.; Banissy, Michael J.; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

2015-01-01

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation—participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. PMID:25481003

Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

PubMed

Brunyé, Tad T; Moran, Joseph M; Holmes, Amanda; Mahoney, Caroline R; Taylor, Holly A

2017-04-01

The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills. Published by Elsevier Inc.

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

PubMed

Craig, Chesney E; Doumas, Michail

2017-01-01

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

Psychosocial work environment and health in U.S. metropolitan areas: a test of the demand-control and demand-control-support models.

PubMed

Muntaner, C; Schoenbach, C

1994-01-01

The authors use confirmatory factor analysis to investigate the psychosocial dimensions of work environments relevant to health outcomes, in a representative sample of five U.S. metropolitan areas. Through an aggregated inference system, scales from Schwartz and associates' job scoring system and from the Dictionary of Occupational Titles (DOT) were employed to examine two alternative models: the demand-control model of Karasek and Theorell and Johnson's demand-control-support model. Confirmatory factor analysis was used to test the two models. The two multidimensional models yielded better fits than an unstructured model. After allowing for the measurement error variance due to the method of assessment (Schwartz and associates' system or DOT), both models yielded acceptable goodness-of-fit indices, but the fit of the demand-control-support model was significantly better. Overall these results indicate that the dimensions of Control (substantive complexity of work, skill discretion, decision authority), Demands (physical exertion, physical demands and hazards), and Social Support (coworker and supervisor social supports) provide an acceptable account of the psychosocial dimensions of work associated with health outcomes.

[Evaluation methods in the work/stress correlations in law enforcement].

PubMed

Magnavital, Nicola; Garbarino, Sergio; Siegrist, Johannes

2014-01-01

Stress in police: assessment methods. Police work is unanimously considered stressful. Prevention of stress in police is of the utmost importance, as a distressed officer could be hazardous for third parties. There is scientific evidence that the relationship between occupational stressors and their psychological and physical consequences can be described by Karasek's demand-control-support (DCS) model and the effort / reward imbalance (ERI) model of Siegrist. This study summarizes the results of surveys conducted using the DCS and ERI questionnaires.on police officers from the VI Mobile Unit of Genoa who were engaged in public order management at the G8 summit in L'Aquila in 2009. In spite of the high alert due to expected threats to public order during the G8 meeting, police officers were not affected by "distress". When the policemen were compared to other categories of workers, their stress levels were in the lowest range. In most cases, the personality profile of these workers did not differ substantially from that of the general population. There was an association between personality and stress response. The levels of perceived stress were significantly associated with absence from work. The prevalence of mental disorders in police officers was significantly lower than that of the general population. Occupational stress was associated with indicators of depression, anxiety and burnout. The DCS and ERI models yielded complementary results and proved to be effective in assessing the effects of stress in law enforcement. The extent of perceived stress does not directly depend on external events, but on the way in which these are handled: routine work may be more stressful than a single critical event. Special police forces are particularly resilient to stress, partly due to the characteristics and personality of individual officers, but mainly on account of their training. Occupational stress is associated with a lower level of psychological well-being and an increase in the frequency of absences from work.

Dimensional comparability of psychosocial working conditions as covered in European monitoring questionnaires.

PubMed

Formazin, Maren; Burr, Hermann; Aagestad, Cecilie; Tynes, Tore; Thorsen, Sannie Vester; Perkio-Makela, Merja; Díaz Aramburu, Clara Isabel; Pinilla García, Francisco Javier; Galiana Blanco, Luz; Vermeylen, Greet; Parent-Thirion, Agnes; Hooftman, Wendela; Houtman, Irene

2014-12-09

In most countries in the EU, national surveys are used to monitor working conditions and health. Since the development processes behind the various surveys are not necessarily theoretical, but certainly practical and political, the extent of similarity among the dimensions covered in these surveys has been unclear. Another interesting question is whether prominent models from scientific research on work and health are present in the surveys--bearing in mind that the primary focus of these surveys is on monitoring status and trends, not on mapping scientific models. Moreover, it is relevant to know which other scales and concepts not stemming from these models have been included in the surveys. The purpose of this paper is to determine (1) the similarity of dimensions covered in the surveys included and (2) the congruence of dimensions of scientific research and of dimensions present in the monitoring systems. Items from surveys representing six European countries and one European wide survey were classified into the dimensions they cover, using a taxonomy agreed upon among all involved partners from the six countries. The classification reveals that there is a large overlap of dimensions, albeit not in the formulation of items, covered in the seven surveys. Among the available items, the two prominent work-stress-models--job-demand-control-support-model (DCS) and effort-reward-imbalance-model (ERI)--are covered in most surveys even though this has not been the primary aim in the compilation of these surveys. In addition, a large variety of items included in the surveillance systems are not part of these models and are--at least partly--used in nearly all surveys. These additional items reflect concepts such as "restructuring", "meaning of work", "emotional demands" and "offensive behaviour/violence & harassment". The overlap of the dimensions being covered in the various questionnaires indicates that the interests of the parties deciding on the questionnaires in the different countries overlap. The large number of dimensions measured in the questionnaires and not being part of the DCS and ERI models is striking. These "new" dimensions could inspire the research community to further investigate their possible health and labour market effects.

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

PubMed Central

Doumas, Michail

2017-01-01

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

Work Stress and Metabolic Syndrome in Police Officers. A Prospective Study

PubMed Central

Garbarino, Sergio; Magnavita, Nicola

2015-01-01

Objective The aim of this longitudinal study was to evaluate the association between occupational stress and metabolic syndrome (MetS) in a rapid response police unit. Method Work-related stress was continuously monitored during the 5-year period with both the Demand-Control-Support (DCS) and the Effort-Reward Imbalance (ERI) models. Blood pressure, body mass index (BMI), waist circumference, triglycerides, HDL-cholesterol, and fasting blood glucose were measured at baseline in January 2009, and in January 2014. 234 out of 290 police officers (81%) completed the follow-up. Results The majority of police officers had high stress levels. At follow-up, police officers in the highest quartile of stress had significantly higher mean levels of triglycerides, and lower levels of HDL-cholesterol than their colleagues in the lowest quartile. Police officers with high stress had an increased adjusted risk of developing MetS (aOR = 2.68; CI95% = 1.08–6.70), and hypertriglyceridemia (aOR = 7.86; CI95 = 1.29–48.04). Demand and Effort were significant predictors of MetS. Conclusion Our study supports the hypothesis that work-related stress induces MetS, particularly through its effects on blood lipids. Future longitudinal studies with continuous monitoring of stress levels will definitively confirm this hypothesis. PMID:26641879

Dendritic cell reprogramming by endogenously produced lactic acid.

PubMed

Nasi, Aikaterini; Fekete, Tünde; Krishnamurthy, Akilan; Snowden, Stuart; Rajnavölgyi, Eva; Catrina, Anca I; Wheelock, Craig E; Vivar, Nancy; Rethi, Bence

2013-09-15

The demand for controlling T cell responses via dendritic cell (DC) vaccines initiated a quest for reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce inflammatory or suppressor programs during differentiation, and we identified a powerful autocrine pathway that, in a cell concentration-dependent manner, strongly interferes with inflammatory DC differentiation. MoDCs developing at low cell culture density have superior ability to produce inflammatory cytokines, to induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no inflammatory cytokines upon activation. DCs from high-density cultures maintained more differentiation plasticity and can develop to osteoclasts. The cell concentration-dependent pathway was independent of peroxisome proliferator-activated receptor γ (PPARγ), a known endogenous regulator of MoDC differentiation. Instead, it acted through lactic acid, which accumulated in dense cultures and induced an early and long-lasting reprogramming of MoDC differentiation. Our results suggest that the lactic acid-mediated inhibitory pathway could be efficiently manipulated in developing MoDCs to influence the immunogenicity of DC vaccines.

Understanding well-being and learning of Nigerian nurses: a job demand control support model approach.

PubMed

van Doorn, Yvonne; van Ruysseveldt, Joris; van Dam, Karen; Mistiaen, Wilhelm; Nikolova, Irina

2016-10-01

This study investigated whether Nigerian nurses' emotional exhaustion and active learning were predicted by job demands, control and social support. Limited research has been conducted concerning nurses' work stress in developing countries, such as Nigeria. Accordingly, it is not clear whether work interventions for improving nurses' well-being in these countries can be based on work stress models that are developed in Western countries, such as the job demand control support model, as well as on empirical findings of job demand control support research. Nurses from Nurses Across the Borders Nigeria were invited to complete an online questionnaire containing validated scales; 210 questionnaires were fully completed and analysed. Multiple regression analysis was used to test the hypotheses. Emotional exhaustion was higher for nurses who experienced high demands and low supervisor support. Active learning occurred when nurses worked under conditions of high control and high supervisor support. The findings suggest that the job demand control support model is applicable in a Nigerian nursing situation; the model indicates which occupational stressors contribute to poor well-being in Nigerian nurses and which work characteristics may boost nurses' active learning. Job (re)design interventions can enhance nurses' well-being and learning by guarding nurses' job demands, and stimulating job control and supervisor support. © 2016 John Wiley & Sons Ltd.

Applying Human Factors Evaluation and Design Guidance to a Nuclear Power Plant Digital Control System

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

Thomas Ulrich; Ronald Boring; William Phoenix

2012-08-01

The United States (U.S.) nuclear industry, like similar process control industries, has moved toward upgrading its control rooms. The upgraded control rooms typically feature digital control system (DCS) displays embedded in the panels. These displays gather information from the system and represent that information on a single display surface. In this manner, the DCS combines many previously separate analog indicators and controls into a single digital display, whereby the operators can toggle between multiple windows to monitor and control different aspects of the plant. The design of the DCS depends on the function of the system it monitors, but revolvesmore » around presenting the information most germane to an operator at any point in time. DCSs require a carefully designed human system interface. This report centers on redesigning existing DCS displays for an example chemical volume control system (CVCS) at a U.S. nuclear power plant. The crucial nature of the CVCS, which controls coolant levels and boration in the primary system, requires a thorough human factors evaluation of its supporting DCS. The initial digital controls being developed for the DCSs tend to directly mimic the former analog controls. There are, however, unique operator interactions with a digital vs. analog interface, and the differences have not always been carefully factored in the translation of an analog interface to a replacement DCS. To ensure safety, efficiency, and usability of the emerging DCSs, a human factors usability evaluation was conducted on a CVCS DCS currently being used and refined at an existing U.S. nuclear power plant. Subject matter experts from process control engineering, software development, and human factors evaluated the DCS displays to document potential usability issues and propose design recommendations. The evaluation yielded 167 potential usability issues with the DCS. These issues should not be considered operator performance problems but rather opportunities identified by experts to improve upon the design of the DCS. A set of nine design recommendations was developed to address these potential issues. The design principles addressed the following areas: (1) color, (2) pop-up window structure, (3) navigation, (4) alarms, (5) process control diagram, (6) gestalt grouping, (7) typography, (8) terminology, and (9) data entry. Visuals illustrating the improved DCS displays accompany the design recommendations. These nine design principles serve as the starting point to a planned general DCS style guide that can be used across the U.S. nuclear industry to aid in the future design of effective DCS interfaces.« less

Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

PubMed

Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

2015-07-01

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. © The Author (2014). Published by Oxford University Press.

A Daily Diary Study of Coping in the Context of the Job Demands-Control-Support Model

ERIC Educational Resources Information Center

Daniels, Kevin; Harris, Claire

2005-01-01

We examined one of the processes thought to underpin Karasek and Theorell's job demands-control-support model (1990). This is that control and support accentuate better well-being by fostering problem-focused coping with work demands. We also examined whether other forms of coping implemented through control and support are related to indicators…

Violence towards health care workers in a Public Health Care Facility in Italy: a repeated cross-sectional study

PubMed Central

2012-01-01

Background Violence at work is one of the major concerns in health care activities. The aim of this study was to identify the prevalence of physical and non-physical violence in a general health care facility in Italy and to assess the relationship between violence and psychosocial factors, thereby providing a basis for appropriate intervention. Methods All health care workers from a public health care facility were invited to complete a questionnaire containing questions on workplace violence. Three questionnaire-based cross-sectional surveys were conducted. The response rate was 75 % in 2005, 71 % in 2007, and 94 % in 2009. The 2009 questionnaire contained the VIF (Violent Incident Form) for reporting violent incidents, the DCS (demand/control/support) model for job strain, the Colquitt 20 item questionnaire for perceived organizational justice, and the GHQ-12 General Health Questionnaire for the assessment of mental health. Results One out of ten workers reported physical assault, and one out of three exposure to non-physical violence in the workplace in the previous year. Nurses and physicians were the most exposed occupational categories, whereas the psychiatric and emergency departments were the services at greatest risk of violence. Workers exposed to non-physical violence were subject to high job strain, low support, low perceived organizational justice, and high psychological distress. Conclusion Our study shows that health care workers in an Italian local health care facility are exposed to violence. Workplace violence was associated with high demand and psychological disorders, while job control, social support and organizational justice were protective factors. PMID:22551645

Effects of tDCS on Bimanual Motor Skills: A Brief Review

PubMed Central

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. PMID:29670514

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

PubMed

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.

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

PubMed

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

2015-01-01

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

Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression.

PubMed

Ho, Kerrie-Anne; Bai, Siwei; Martin, Donel; Alonzo, Angelo; Dokos, Socrates; Loo, Colleen K

2015-12-01

This study aimed to examine a bitemporal (BT) transcranial direct current stimulation (tDCS) electrode montage for the treatment of depression through a clinical pilot study and computational modeling. The safety of repeated courses of stimulation was also examined. Four participants with depression who had previously received multiple courses of tDCS received a 4-week course of BT tDCS. Mood and neuropsychological function were assessed. The results were compared with previous courses of tDCS given to the same participants using different electrode montages. Computational modeling examined the electric field maps produced by the different montages. Three participants showed clinical improvement with BT tDCS (mean [SD] improvement, 49.6% [33.7%]). There were no adverse neuropsychological effects. Computational modeling showed that the BT montage activates the anterior cingulate cortices and brainstem, which are deep brain regions that are important for depression. However, a fronto-extracephalic montage stimulated these areas more effectively. No adverse effects were found in participants receiving up to 6 courses of tDCS. Bitemporal tDCS was safe and led to clinically meaningful efficacy in 3 of 4 participants. However, computational modeling suggests that the BT montage may not activate key brain regions in depression more effectively than another novel montage--fronto-extracephalic tDCS. There is also preliminary evidence to support the safety of up to 6 repeated courses of tDCS.

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

PubMed

Hammer, Gianna Elena; Ma, Averil

2013-01-01

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

CD8+ T Cells Orchestrate pDC-XCR1+ Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming.

PubMed

Brewitz, Anna; Eickhoff, Sarah; Dähling, Sabrina; Quast, Thomas; Bedoui, Sammy; Kroczek, Richard A; Kurts, Christian; Garbi, Natalio; Barchet, Winfried; Iannacone, Matteo; Klauschen, Frederick; Kolanus, Waldemar; Kaisho, Tsuneyasu; Colonna, Marco; Germain, Ronald N; Kastenmüller, Wolfgang

2017-02-21

Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8 + T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8 + T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine. Functionally, this CD8 + T cell-mediated reorganization of the local DC network allowed for the interaction and cooperation of pDCs and XCR1 + DCs, thereby optimizing XCR1 + DC maturation and cross-presentation. These data support a model in which CD8 + T cells upon activation create their own optimal priming microenvironment by recruiting additional DC subsets to the site of initial antigen recognition. Published by Elsevier Inc.

Relative effects of demand and control on task-related cardiovascular reactivity, task perceptions, performance accuracy, and mood.

PubMed

Flynn, Niamh; James, Jack E

2009-05-01

The hypothesis that work control has beneficial effects on well-being is the basis of the widely applied, yet inconsistently supported, Job Demand Control (JDC) Model [Karasek, R.A., 1979. Job demands, job decision latitude and mental strain: Implications for job redesign. Adm. Sci. Q. 24, 285-308.; Karasek, R., Theorell, T., 1990. Healthy Work: Stress, Productivity, and the Reconstruction of Working Life. Basic Books, Oxford]. The model was tested in an experiment (N=60) using a cognitive stressor paradigm that sought to prevent confounding between demand and control. High-demand was found to be associated with deleterious effects on physiological, subjective, and performance outcomes. In contrast, few main effects were found for control. Evidence for the buffer interpretation of the JDC Model was limited to a significant demand-control interaction for performance accuracy, whereas substantial support was found for the strain interpretation of the model [van der Doef, M., Maes, S., 1998. The job demand-control(-support) model and physical health outcomes: A review of the strain and buffer hypotheses. Psychol. Health 13, 909-936., van der Doef, M., Maes, S., 1999. The Job Demand-Control(-Support) model and psychological well-being: A review of 20 years of empirical research. Work Stress 13, 87-114]. Manipulation checks revealed that objective control altered perceptions of control but not perceptions of demand. It is suggested that beneficial effects of work-related control are unlikely to occur in the absence of reductions in perceived demand. Thus, contrary to the propositions of Karasek and colleagues, demand and control do not appear to be independent factors.

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

PubMed

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

2016-09-01

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

Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats.

PubMed

Jackson, Mark P; Truong, Dennis; Brownlow, Milene L; Wagner, Jessica A; McKinley, R Andy; Bikson, Marom; Jankord, Ryan

2017-08-01

A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5mA for 60min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5mA using a 25.0mm 2 electrode (electrode current density: 20.0A/m 2 ). Lesion initially occurred using smaller 10.6mm 2 or 5.3mm 2 electrodes at 0.25mA (23.5A/m 2 ) and 0.5mA (94.2A/m 2 ), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0A/m 2 , which is below the previously reported safety threshold of 142.9A/m 2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0A/m 2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2A/m 2 when electrodes are placed on the skin (resulting in a lower brain current density). Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-08-01

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

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

PubMed

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

2015-08-01

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

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

PubMed

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

2015-10-01

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

Multiple-function multi-input/multi-output digital control and on-line analysis

NASA Technical Reports Server (NTRS)

Hoadley, Sherwood T.; Wieseman, Carol D.; Mcgraw, Sandra M.

1992-01-01

The design and capabilities of two digital controller systems for aeroelastic wind-tunnel models are described. The first allowed control of flutter while performing roll maneuvers with wing load control as well as coordinating the acquisition, storage, and transfer of data for on-line analysis. This system, which employs several digital signal multi-processor (DSP) boards programmed in high-level software languages, is housed in a SUN Workstation environment. A second DCS provides a measure of wind-tunnel safety by functioning as a trip system during testing in the case of high model dynamic response or in case the first DCS fails. The second DCS uses National Instruments LabVIEW Software and Hardware within a Macintosh environment.

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

PubMed

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

2016-01-01

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

Mast Cells Condition Dendritic Cells to Mediate Allograft Tolerance

PubMed Central

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

2013-01-01

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

Modelling the electric field and the current density generated by cerebellar transcranial DC stimulation in humans.

PubMed

Parazzini, Marta; Rossi, Elena; Ferrucci, Roberta; Liorni, Ilaria; Priori, Alberto; Ravazzani, Paolo

2014-03-01

Transcranial Direct Current Stimulation (tDCS) over the cerebellum (or cerebellar tDCS) modulates working memory, changes cerebello-brain interaction, and affects locomotion in humans. Also, the use of tDCS has been proposed for the treatment of disorders characterized by cerebellar dysfunction. Nonetheless, the electric field (E) and current density (J) spatial distributions generated by cerebellar tDCS are unknown. This work aimed to estimate E and J distributions during cerebellar tDCS. Computational electromagnetics techniques were applied in three human realistic models of different ages and gender. The stronger E and J occurred mainly in the cerebellar cortex, with some spread (up to 4%) toward the occipital cortex. Also, changes by ±1cm in the position of the active electrode resulted in a small effect (up to 4%) in the E and J spatial distribution in the cerebellum. Finally, the E and J spreads to the brainstem and the heart were negligible, thus further supporting the safety of this technique. Despite inter-individual differences, our modeling study confirms that the cerebellum is the structure mainly involved by cerebellar tDCS. Modeling approach reveals that during cerebellar tDCS the current spread to other structures outside the cerebellum is unlike to produce functional effects. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2018-01-01

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

A Probability Model of Decompression Sickness at 4.3 Psia after Exercise Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, Johnny; Gernhardt, Michael L.; Powell, Michael R.; Pollock, Neal

2004-01-01

Exercise PB can reduce the risk of decompression sickness on ascent to 4.3 psia when performed at the proper intensity and duration. Data are from seven tests. PB times ranged from 90 to 150 min. High intensity, short duration dual-cycle ergometry was done during the PB. This was done alone, or combined with intermittent low intensity exercise or periods of rest for the remaining PB. Nonambulating men and women performed light exercise from a semi-recumbent position at 4.3 psia for four hrs. The Research Model with age tested the probability that DCS increases with advancing age. The NASA Model with gender hypothesized that the probability of DCS increases if gender is female. Accounting for exercise and rest during PB with a variable half-time compartment for computed tissue N2 pressure advances our probability modeling of hypobaric DCS. Both models show that a small increase in exercise intensity during PB reduces the risk of DCS, and a larger increase in exercise intensity dramatically reduces risk. These models support the hypothesis that aerobic fitness is an important consideration for the risk of hypobaric DCS when exercise is performed during the PB.

Testing the Job Demand-Control-Support model with anxiety and depression as outcomes: the Hordaland Health Study.

PubMed

Sanne, Bjarte; Mykletun, Arnstein; Dahl, Alv A; Moen, Bente E; Tell, Grethe S

2005-09-01

To test the strain/iso-strain, interaction and buffer hypotheses of the Job Demand-Control-Support model in relation to anxiety and depression. Five thousand five hundred and sixty-two workers with valid Demand-Control-Support Questionnaire (DCSQ) scores were examined with the sub-scales of the Hospital Anxiety and Depression Scale as outcomes. Multiple statistical methods were applied. The strain and iso-strain hypotheses were confirmed. Generally, additive and non-interaction effects were found between psychological demands, control and social support. The buffer hypotheses were refuted. Results from analyses testing different interaction operationalizations were complementary. High demands, low control and low support individually, but particularly combined, are risk factors for anxiety and depression. Support is the DCSQ index most strongly associated with anxiety and depression in women. Assessment of psychosocial work environment may identify workers at risk, and serve as a basis for job-redesign.

Space Flight Decompression Sickness Contingency Plan

NASA Technical Reports Server (NTRS)

Dervay, Joseph; Gernhardt, Michael L.; Ross, Charles E.; Hamilton, Douglas; Homick, Jerry L. (Technical Monitor)

2000-01-01

The purpose was to develop an enhanced plan to diagnose, treat, and manage decompression sickness (DCS) during extravehicular activity (EVA). This plan is merited by the high frequency of upcoming EVAs necessary to construct and maintain the International Space Station (ISS). The upcoming ISS era will demand a significant increase in EVA. The DCS Risk and Contingency Plan provided a new and improved approach to DCS reporting, treatment, management, and training.

A longitudinal test of the demand-control model using specific job demands and specific job control.

PubMed

de Jonge, Jan; van Vegchel, Natasja; Shimazu, Akihito; Schaufeli, Wilmar; Dormann, Christian

2010-06-01

Supportive studies of the demand-control (DC) model were more likely to measure specific demands combined with a corresponding aspect of control. A longitudinal test of Karasek's (Adm Sci Q. 24:285-308, 1) job strain hypothesis including specific measures of job demands and job control, and both self-report and objectively recorded well-being. Job strain hypothesis was tested among 267 health care employees from a two-wave Dutch panel survey with a 2-year time lag. Significant demand/control interactions were found for mental and emotional demands, but not for physical demands. The association between job demands and job satisfaction was positive in case of high job control, whereas this association was negative in case of low job control. In addition, the relation between job demands and psychosomatic health symptoms/sickness absence was negative in case of high job control and positive in case of low control. Longitudinal support was found for the core assumption of the DC model with specific measures of job demands and job control as well as self-report and objectively recorded well-being.

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

PubMed

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

2014-07-01

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

Brucella discriminates between mouse dendritic cell subsets upon in vitro infection.

PubMed

Papadopoulos, Alexia; Gagnaire, Aurélie; Degos, Clara; de Chastellier, Chantal; Gorvel, Jean-Pierre

2016-01-01

Brucella is a Gram-negative bacterium responsible for brucellosis, a worldwide re-emerging zoonosis. Brucella has been shown to infect and replicate within Granulocyte macrophage colony-stimulating factor (GMCSF) in vitro grown bone marrow-derived dendritic cells (BMDC). In this cell model, Brucella can efficiently control BMDC maturation. However, it has been shown that Brucella infection in vivo induces spleen dendritic cells (DC) migration and maturation. As DCs form a complex network composed by several subpopulations, differences observed may be due to different interactions between Brucella and DC subsets. Here, we compare Brucella interaction with several in vitro BMDC models. The present study shows that Brucella is capable of replicating in all the BMDC models tested with a high infection rate at early time points in GMCSF-IL15 DCs and Flt3l DCs. GMCSF-IL15 DCs and Flt3l DCs are more activated than the other studied DC models and consequently intracellular bacteria are not efficiently targeted to the ER replicative niche. Interestingly, GMCSF-DC and GMCSF-Flt3l DC response to infection is comparable. However, the key difference between these 2 models concerns IL10 secretion by GMCSF DCs observed at 48 h post-infection. IL10 secretion can explain the weak secretion of IL12p70 and TNFα in the GMCSF-DC model and the low level of maturation observed when compared to GMCSF-IL15 DCs and Flt3l DCs. These models provide good tools to understand how Brucella induce DC maturation in vivo and may lead to new therapeutic design using DCs as cellular vaccines capable of enhancing immune response against pathogens.

Transcranial Direct Current Brain Stimulation Increases Ability to Resist Smoking.

PubMed

Falcone, Mary; Bernardo, Leah; Ashare, Rebecca L; Hamilton, Roy; Faseyitan, Olufunsho; McKee, Sherry A; Loughead, James; Lerman, Caryn

2016-01-01

The ability to exert self-control over temptation is a fundamental component of smoking behavior change. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to modulate cognitive control circuits. Although prior studies show that stimulation reduces cigarette craving and self-reported smoking, effects on ability to resist smoking have not been investigated directly. We assessed effects of a single 20-minute session of 1.0 mA anodal stimulation over the left DLPFC with cathodal stimulation over the right supra-orbital area (vs. sham stimulation) on ability to resist smoking in a validated smoking lapse paradigm. Twenty-five participants completed two tDCS sessions (active and sham stimulation) in a within-subject, double-blind, randomized and counterbalanced order with a 2-week washout period. Following overnight abstinence, participants received tDCS in the presence of smoking related cues; they had the option to smoke at any time or receive $1 for every 5 minutes they abstained. After 50 minutes, they participated in a 1 hour ad libitum smoking session. Primary and secondary outcomes were time to first cigarette and cigarette consumption, respectively. In multiple regression models, active tDCS (compared to sham) significantly increased latency to smoke (p = 0.02) and decreased the total number of cigarettes smoked (p = 0.014) during the session. These findings suggest that acute anodal stimulation over the left DLPFC (with cathodal stimulation over the right supra-orbital area) can improve ability to resist smoking, supporting the therapeutic potential of tDCS for smoking cessation treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-01-01

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

Mechanisms and Effects of Transcranial Direct Current Stimulation

PubMed Central

Giordano, James; Bikson, Marom; Kappenman, Emily S.; Clark, Vincent P.; Coslett, H. Branch; Hamblin, Michael R.; Hamilton, Roy; Jankord, Ryan; Kozumbo, Walter J.; McKinley, R. Andrew; Nitsche, Michael A.; Reilly, J. Patrick; Richardson, Jessica; Wurzman, Rachel

2017-01-01

The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged. PMID:28210202

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

NASA Technical Reports Server (NTRS)

Conkin, J.; Pilmanis, A. A.

2010-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-14

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

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

PubMed

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

2018-04-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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.

Modeling the effects of exercise during 100% oxygen prebreathe on the risk of hypobaric decompression sickness

NASA Technical Reports Server (NTRS)

Loftin, K. C.; Conkin, J.; Powell, M. R.

1997-01-01

BACKGROUND: Several previous studies indicated that exercise during prebreathe with 100% O2 decreased the incidence of hypobaric decompression sickness (DCS). We report a meta-analysis of these investigations combined with a new study in our laboratory to develop a statistical model as a predictive tool for DCS. HYPOTHESIS: Exercise during prebreathe increases N2 elimination in a theoretical 360-min half-time compartment decreasing the incidence of DCS. METHODS: A dose-response probability tissue ratio (TR) model with 95% confidence limits was created for two groups, prebreathe with exercise (n = 113) and resting prebreathe (n = 113), using nonlinear regression analysis with maximum likelihood optimization. RESULTS: The model predicted that prebreathe exercise would reduce the residual N2 in a 360-min half-time compartment to a level analogous to that in a 180-min compartment. This finding supported the hypothesis. The incidence of DCS for the exercise prebreathe group was significantly decreased (Chi-Square = 17.1, p < 0.0001) from the resting prebreathe group. CONCLUSIONS: The results suggested that exercise during prebreathe increases tissue perfusion and N2 elimination approximately 2-fold and markedly lowers the risk of DCS. Based on the model, the prebreathe duration may be reduced from 240 min to a predicted 91 min for the protocol in our study, but this remains to be verified. The model provides a useful planning tool to develop and test appropriate prebreathe exercise protocols and to predict DCS risks for astronauts.

Using Transcranial Direct Current Stimulation to Enhance Creative Cognition: Interactions between Task, Polarity, and Stimulation Site

PubMed Central

Weinberger, Adam B.; Green, Adam E.; Chrysikou, Evangelia G.

2017-01-01

Creative cognition is frequently described as involving two primary processes, idea generation and idea selection. A growing body of research has used transcranial direct current stimulation (tDCS) to examine the neural mechanisms implicated in each of these processes. This literature has yielded a diverse set of findings that vary depending on the location and type (anodal, cathodal, or both) of electrical stimulation employed, as well as the task’s reliance on idea generation or idea selection. As a result, understanding the interactions between stimulation site, polarity and task demands is required to evaluate the potential of tDCS to enhance creative performance. Here, we review tDCS designs that have elicited reliable and dissociable enhancements for creative cognition. Cathodal stimulation over the left inferior frontotemporal cortex has been associated with improvements on tasks that rely primarily on idea generation, whereas anodal tDCS over left dorsolateral prefrontal cortex (DLPFC) and frontopolar cortex has been shown to augment performance on tasks that impose high demands on creative idea selection. These results highlight the functional selectivity of tDCS for different components of creative thinking and confirm the dissociable contributions of left dorsal and inferior lateral frontotemporal cortex for different creativity tasks. We discuss promising avenues for future research that can advance our understanding of the effectiveness of tDCS as a method to enhance creative cognition. PMID:28559804

Effects of transcranial direct current stimulation over the supplementary motor area body weight-supported treadmill gait training in hemiparetic patients after stroke.

PubMed

Manji, Atsushi; Amimoto, Kazu; Matsuda, Tadamitsu; Wada, Yoshiaki; Inaba, Akira; Ko, Sangkyun

2018-01-01

Transcranial direct current stimulation (tDCS) is used in a variety of disorders after stroke including upper limb motor dysfunctions, hemispatial neglect, aphasia, and apraxia, and its effectiveness has been demonstrated. Although gait ability is important for daily living, there were few reports of the use of tDCS to improve balance and gait ability. The supplementary motor area (SMA) was reported to play a potentially important role in balance recovery after stroke. We aimed to investigate the effect of combined therapy body weight-supported treadmill training (BWSTT) and tDCS on gait function recovery of stroke patients. Thirty stroke inpatients participated in this study. The two BWSTT periods of 1weeks each, with real tDCS (anode: front of Cz, cathode: inion, 1mA, 20min) on SMA and sham stimulation, were randomized in a double-blind crossover design. We measured the time required for the 10m Walk Test (10MWT) and Timed Up and Go (TUG) test before and after each period. We found that the real tDCS with BWSTT significantly improved gait speed (10MWT) and applicative walking ability (TUG), compared with BWSTT+sham stimulation periods (p<0.05). Our findings demonstrated the feasibility and efficacy of tDCS in gait training after stroke. The facilitative effects of tDCS on SMA possibly improved postural control during BWSTT. The results indicated the implications for the use of tDCS in balance and gait training rehabilitation after stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

Job characteristics and safety climate: the role of effort-reward and demand-control-support models.

PubMed

Phipps, Denham L; Malley, Christine; Ashcroft, Darren M

2012-07-01

While safety climate is widely recognized as a key influence on organizational safety, there remain questions about the nature of its antecedents. One potential influence on safety climate is job characteristics (that is, psychosocial features of the work environment). This study investigated the relationship between two job characteristics models--demand-control-support (Karasek & Theorell, 1990) and effort-reward imbalance (Siegrist, 1996)--and safety climate. A survey was conducted with a random sample of 860 British retail pharmacists, using the job contents questionnaire (JCQ), effort-reward imbalance indicator (ERI) and a measure of safety climate in pharmacies. Multivariate data analyses found that: (a) both models contributed to the prediction of safety climate ratings, with the demand-control-support model making the largest contribution; (b) there were some interactions between demand, control and support from the JCQ in the prediction of safety climate scores. The latter finding suggests the presence of "active learning" with respect to safety improvement in high demand, high control settings. The findings provide further insight into the ways in which job characteristics relate to safety, both individually and at an aggregated level.

Anodal Transcranial Direct Current Stimulation Enhances Survival and Integration of Dopaminergic Cell Transplants in a Rat Parkinson Model.

PubMed

Winkler, Christian; Reis, Janine; Hoffmann, Nadin; Gellner, Anne-Kathrin; Münkel, Christian; Curado, Marco Rocha; Furlanetti, Luciano; Garcia, Joanna; Döbrössy, Máté D; Fritsch, Brita

2017-01-01

Restorative therapy concepts, such as cell based therapies aim to restitute impaired neurotransmission in neurodegenerative diseases. New strategies to enhance grafted cell survival and integration are still needed to improve functional recovery. Anodal direct current stimulation (DCS) promotes neuronal activity and secretion of the trophic factor BDNF in the motor cortex. Transcranial DCS applied to the motor cortex transiently improves motor symptoms in Parkinson's disease (PD) patients. In this proof-of-concept study, we combine cell based therapy and noninvasive neuromodulation to assess whether neurotrophic support via transcranial DCS would enhance the restitution of striatal neurotransmission by fetal dopaminergic transplants in a rat Parkinson model. Transcranial DCS was applied daily for 20 min on 14 consecutive days following striatal transplantation of fetal ventral mesencephalic (fVM) cells derived from transgenic rat embryos ubiquitously expressing GFP. Anodal but not cathodal transcranial DCS significantly enhanced graft survival and dopaminergic reinnervation of the surrounding striatal tissue relative to sham stimulation. Behavioral recovery was more pronounced following anodal transcranial DCS, and behavioral effects correlated with the degree of striatal innervation. Our results suggest anodal transcranial DCS may help advance cell-based restorative therapies in neurodegenerative diseases. In particular, such an assistive approach may be beneficial for the already established cell transplantation therapy in PD.

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

PubMed

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

2015-07-01

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

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

PubMed

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

2011-12-01

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

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

PubMed

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

2017-08-01

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

An Experience Sampling Study of Learning, Affect, and the Demands Control Support Model

ERIC Educational Resources Information Center

Daniels, Kevin; Boocock, Grahame; Glover, Jane; Hartley, Ruth; Holland, Julie

2009-01-01

The demands control support model (R. A. Karasek & T. Theorell, 1990) indicates that job control and social support enable workers to engage in problem solving. In turn, problem solving is thought to influence learning and well-being (e.g., anxious affect, activated pleasant affect). Two samples (N = 78, N = 106) provided data up to 4 times per…

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

PubMed Central

Edwards, Dylan; Cortes, Mar; Datta, Abhishek; Minhas, Preet; Wassermann, Eric M.; Bikson, Marom

2015-01-01

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation. PMID:23370061

No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults.

PubMed

Külzow, Nadine; Cavalcanti de Sousa, Angelica Vieira; Cesarz, Magda; Hanke, Julie-Marie; Günsberg, Alida; Harder, Solvejg; Koblitz, Swantje; Grittner, Ulrike; Flöel, Agnes

2017-01-01

Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and a non-optimal timing of atDCS between sessions might have masked beneficial effects and should be more systematically addressed in future studies.

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

PubMed Central

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

2010-01-01

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

A Longitudinal Test of the Demand–Control Model Using Specific Job Demands and Specific Job Control

PubMed Central

van Vegchel, Natasja; Shimazu, Akihito; Schaufeli, Wilmar; Dormann, Christian

2010-01-01

Background Supportive studies of the demand–control (DC) model were more likely to measure specific demands combined with a corresponding aspect of control. Purpose A longitudinal test of Karasek’s (Adm Sci Q. 24:285–308, 1) job strain hypothesis including specific measures of job demands and job control, and both self-report and objectively recorded well-being. Method Job strain hypothesis was tested among 267 health care employees from a two-wave Dutch panel survey with a 2-year time lag. Results Significant demand/control interactions were found for mental and emotional demands, but not for physical demands. The association between job demands and job satisfaction was positive in case of high job control, whereas this association was negative in case of low job control. In addition, the relation between job demands and psychosomatic health symptoms/sickness absence was negative in case of high job control and positive in case of low control. Conclusion Longitudinal support was found for the core assumption of the DC model with specific measures of job demands and job control as well as self-report and objectively recorded well-being. PMID:20195810

Technical innovations that may facilitate real-time telementoring of damage control surgery in austere environments: a proof of concept comparative evaluation of the importance of surgical experience, telepresence, gravity and mentoring in the conduct of damage control laparotomies.

PubMed

Kirkpatrick, Andrew W; LaPorta, Anthony; Brien, Susan; Leslie, Tim; Glassberg, Elon; McKee, Jessica; Ball, Chad G; Wright Beatty, Heather E; Keillor, Jocelyn; Roberts, Derek J; Tien, Homer

2015-06-01

Bleeding to death is the most preventable cause of posttraumatic death worldwide. Despite the fact that many of these deaths are anatomically salvageable with relatively basic surgical interventions, they remain lethal in actuality in prehospital environments when no facilities and skills exist to contemplate undertaking basic damage control surgery (DCS). With better attention to prehospital control of extremity hemorrhage, intracavitary bleeding (especially intraperitoneal) remains beyond the scope of prehospital providers. However, recent revolutions in the informatics and techniques of telementoring (TMT), DCS and highly realistic accelerated training of motivated first responders suggests that basic lifesaving DCS may have applicability to save bleeding patients in austere environments previously considered unsalvageable. Especially with informatic advances, any provider with Internet connectivity can potentially be supported by highly proficient specialists with content expertise in the index problem. This unprecedented TMT support may allow highly motivated but inexperienced personnel to provide advanced surgical interventions in extreme environments in many austere locations both on and above the planet.

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

PubMed

Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

2015-07-01

Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

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

PubMed

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

2017-07-01

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

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

PubMed

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

2000-04-01

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

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

PubMed

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

2018-05-01

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

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

PubMed

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

The probability and severity of decompression sickness

PubMed Central

Hada, Ethan A.; Vann, Richard D.; Denoble, Petar J.

2017-01-01

Decompression sickness (DCS), which is caused by inert gas bubbles in tissues, is an injury of concern for scuba divers, compressed air workers, astronauts, and aviators. Case reports for 3322 air and N2-O2 dives, resulting in 190 DCS events, were retrospectively analyzed and the outcomes were scored as (1) serious neurological, (2) cardiopulmonary, (3) mild neurological, (4) pain, (5) lymphatic or skin, and (6) constitutional or nonspecific manifestations. Following standard U.S. Navy medical definitions, the data were grouped into mild—Type I (manifestations 4–6)–and serious–Type II (manifestations 1–3). Additionally, we considered an alternative grouping of mild–Type A (manifestations 3–6)–and serious–Type B (manifestations 1 and 2). The current U.S. Navy guidance allows for a 2% probability of mild DCS and a 0.1% probability of serious DCS. We developed a hierarchical trinomial (3-state) probabilistic DCS model that simultaneously predicts the probability of mild and serious DCS given a dive exposure. Both the Type I/II and Type A/B discriminations of mild and serious DCS resulted in a highly significant (p << 0.01) improvement in trinomial model fit over the binomial (2-state) model. With the Type I/II definition, we found that the predicted probability of ‘mild’ DCS resulted in a longer allowable bottom time for the same 2% limit. However, for the 0.1% serious DCS limit, we found a vastly decreased allowable bottom dive time for all dive depths. If the Type A/B scoring was assigned to outcome severity, the no decompression limits (NDL) for air dives were still controlled by the acceptable serious DCS risk limit rather than the acceptable mild DCS risk limit. However, in this case, longer NDL limits were allowed than with the Type I/II scoring. The trinomial model mild and serious probabilities agree reasonably well with the current air NDL only with the Type A/B scoring and when 0.2% risk of serious DCS is allowed. PMID:28296928

Anodal Transcranial Direct Current Stimulation Enhances Survival and Integration of Dopaminergic Cell Transplants in a Rat Parkinson Model

PubMed Central

Winkler, Christian; Reis, Janine; Hoffmann, Nadin; Gellner, Anne-Kathrin; Münkel, Christian; Curado, Marco Rocha

2017-01-01

Abstract Restorative therapy concepts, such as cell based therapies aim to restitute impaired neurotransmission in neurodegenerative diseases. New strategies to enhance grafted cell survival and integration are still needed to improve functional recovery. Anodal direct current stimulation (DCS) promotes neuronal activity and secretion of the trophic factor BDNF in the motor cortex. Transcranial DCS applied to the motor cortex transiently improves motor symptoms in Parkinson’s disease (PD) patients. In this proof-of-concept study, we combine cell based therapy and noninvasive neuromodulation to assess whether neurotrophic support via transcranial DCS would enhance the restitution of striatal neurotransmission by fetal dopaminergic transplants in a rat Parkinson model. Transcranial DCS was applied daily for 20 min on 14 consecutive days following striatal transplantation of fetal ventral mesencephalic (fVM) cells derived from transgenic rat embryos ubiquitously expressing GFP. Anodal but not cathodal transcranial DCS significantly enhanced graft survival and dopaminergic reinnervation of the surrounding striatal tissue relative to sham stimulation. Behavioral recovery was more pronounced following anodal transcranial DCS, and behavioral effects correlated with the degree of striatal innervation. Our results suggest anodal transcranial DCS may help advance cell-based restorative therapies in neurodegenerative diseases. In particular, such an assistive approach may be beneficial for the already established cell transplantation therapy in PD. PMID:28966974

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

PubMed

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

2016-11-01

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

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

PubMed

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

2016-07-18

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder, with the severity of the disability usually increasing with disease duration. IPD affects patients' health-related quality of life, disability, and impairment. Current rehabilitation approaches have limited effectiveness in improving outcomes in patients with IPD, but a possible adjunct to rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in IPD. To assess the effectiveness of tDCS in improving motor and non-motor symptoms in people with IPD. We searched the following databases (until February 2016): the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library ; 2016 , Issue 2), MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index, the Physiotherapy Evidence Database (PEDro), Rehabdata, and Inspec. In an effort to identify further published, unpublished, and ongoing trials, we searched trial registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials that compared tDCS versus control in patients with IPD for improving health-related quality of life , disability, and impairment. Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. We included six trials with a total of 137 participants. We found two studies with 45 participants examining the effects of tDCS compared to control (sham tDCS) on our primary outcome measure, impairment, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). There was very low quality evidence for no effect of tDCS on change in global UPDRS score ( mean difference (MD) -7.10 %, 95% confidence interval (CI -19.18 to 4.97; P = 0.25, I² = 21%, random-effects model). However, there was evidence of an effect on UPDRS part III motor subsection score at the end of the intervention phase (MD -14.43%, 95% CI -24.68 to -4.18; P = 0.006, I² = 2%, random-effects model; very low quality evidence). One study with 25 participants measured the reduction in off and on time with dyskinesia, but there was no evidence of an effect (MD 0.10 hours, 95% CI -0.14 to 0.34; P = 0.41, I² = 0%, random-effects model; and MD 0.00 hours, 95% CI -0.12 to 0.12; P = 1, I² = 0%, random- effects model, respectively; very low quality evidence).Two trials with a total of 41 participants measured gait speed using measures of timed gait at the end of the intervention phase, revealing no evidence of an effect ( standardised mean difference (SMD) 0.50, 95% CI -0.17 to 1.18; P = 0.14, I² = 11%, random-effects model; very low quality evidence). Another secondary outcome was health-related quality of life and we found one study with 25 participants reporting on the physical health and mental health aspects of health-related quality of life (MD 1.00 SF-12 score, 95% CI -5.20 to 7.20; I² = 0%, inverse variance method with random-effects model; very low quality evidence; and MD 1.60 SF-12 score, 95% CI -5.08 to 8.28; I² = 0%, inverse variance method with random-effects model; very low quality evidence, respectively). We found no study examining the effects of tDCS for improving activities of daily living. In two of six studies, dropouts , adverse events, or deaths occurring during the intervention phase were reported. There was insufficient evidence that dropouts , adverse effects, or deaths were higher with intervention (risk difference (RD) 0.04, 95% CI -0.05 to 0.12; P = 0.40, I² = 0%, random-effects model; very low quality evidence).We found one trial with a total of 16 participants examining the effects of tDCS plus movement therapy compared to control (sham tDCS) plus movement therapy on our secondary outcome, gait speed at the end of the intervention phase, revealing no evidence of an effect (MD 0.05 m/s, 95% CI -0.15 to 0.25; inverse variance method with random-effects model; very low quality evidence). We found no evidence of an effect regarding differences in dropouts and adverse effects between intervention and control groups (RD 0.00, 95% CI -0.21 to 0.21; Mantel-Haenszel method with random-effects model; very low quality evidence). There is insufficient evidence to determine the effects of tDCS for reducing off time ( when the symptoms are not controlled by the medication) and on time with dyskinesia ( time that symptoms are controlled but the person still experiences involuntary muscle movements ) , and for improving health- related quality of life, disability, and impairment in patients with IPD. Evidence of very low quality indicates no difference in dropouts and adverse events between tDCS and control groups.

Job Strain and Self-Reported Insomnia Symptoms among Nurses: What about the Influence of Emotional Demands and Social Support?

PubMed

Portela, Luciana Fernandes; Kröning Luna, Caroline; Rotenberg, Lúcia; Silva-Costa, Aline; Toivanen, Susanna; Araújo, Tania; Griep, Rosane Härter

2015-01-01

Job strain, derived from high psychological demands and low job control, is associated with insomnia, but information on the role of emotional demands and social support in this relationship is scarce. The aims of this study were (i) to test the association between job strain and self-reported insomnia symptoms, (ii) to evaluate the combination of emotional demands and job control regarding insomnia symptoms, and (iii) to analyze the influence of social support in these relationships. This cross-sectional study refers to a sample of nurses (N = 3,013 and N = 3,035 for Job Strain and Emotional demand-control model, resp.) working at public hospitals in Rio de Janeiro, Brazil. Data were collected through a self-report questionnaire. The prevalence of insomnia symptoms was 34.3%. Job strain was associated with increased odds for insomnia symptoms (OR: 2.20); the same result was observed with the combination of emotional demands and low job control (OR: 1.99). In both models, the inclusion of low social support combined with high demands and low job control led to increased odds for insomnia symptoms, compared to groups with high social support from coworkers and supervisors. Besides job strain, the study of emotional demands and social support are promising with regards to insomnia symptoms, particularly among nurses.

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

PubMed

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 and enhancing cognitive functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-01

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

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

PubMed

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

2016-01-01

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

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

PubMed

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.

Non-invasive Prefrontal/Frontal Brain Stimulation Is Not Effective in Modulating Food Reappraisal Abilities or Calorie Consumption in Obese Females

PubMed Central

Grundeis, Felicitas; Brand, Cristin; Kumar, Saurabh; Rullmann, Michael; Mehnert, Jan; Pleger, Burkhard

2017-01-01

Background/Objectives: Previous studies suggest that non-invasive transcranial direct current stimulation (tDCS) applied to the prefrontal cortex modulates food choices and calorie intake in obese humans. Participants/Methods: In the present fully randomized, placebo-controlled, within-subject and double-blinded study, we applied single sessions of anodal, cathodal, and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) and contralateral frontal operculum in 25 hungry obese women and investigated possible influences on food reappraisal abilities as well as calorie intake. We hypothesized that tDCS, (i) improves the ability to regulate the desire for visually presented foods and, (ii) reduces their consumption. Results: We could not confirm an effect of anodal or cathodal tDCS, neither on the ability to modulate the desire for visually presented foods, nor on calorie consumption. Conclusions: The present findings do not support the notion of prefrontal/frontal tDCS as a promising treatment option for obesity. PMID:28676735

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

PubMed

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

2010-02-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Consequences of Cathodal Stimulation for Behavior: When Does It Help and When Does It Hurt Performance?

PubMed Central

Nozari, Nazbanou; Woodard, Kristina; Thompson-Schill, Sharon L.

2014-01-01

Cathodal Transcranial Direct Current Stimulation (C-tDCS) has been reported, across different studies, to facilitate or hinder performance, or simply to have no tangible effect on behavior. This discrepancy is most prominent when C-tDCS is used to alter a cognitive function, questioning the assumption that cathodal stimulation always compromises performance. In this study, we aimed to study the effect of two variables on performance in a simple cognitive task (letter Flanker), when C-tDCS was applied to the left prefrontal cortex (PFC): (1) the time of testing relative to stimulation (during or after), and (2) the nature of the cognitive activity during stimulation in case of post-tDCS testing. In three experiments, we had participants either perform the Flanker task during C-tDCS (Experiment 1), or after C-tDCS. When the Flanker task was administered after C-tDCS, we varied whether during stimulation subjects were engaged in activities that posed low (Experiment 2) or high (Experiment 3) demands on the PFC. Our findings show that the nature of the task during C-tDCS has a systematic influence on the outcome, while timing per se does not. PMID:24409291

Students' well-being in nursing undergraduate education.

PubMed

Tuomi, Jouni; Aimala, Anna-Mari; Plazar, Nadja; Starčič, Andreja Istenič; Žvanut, Boštjan

2013-06-01

Although previously the Job-Demand-Control-Support model has been successfully applied in many studies in the field of health care and education, the model was never used for the evaluation of the nursing students' well-being. The aim of this study was to promote nursing students' well-being. The objective was to verify whether the Job-Demand-Control-Support model is appropriate for the evaluation of their well-being. The Job-Demand-Control-Support model was implemented and investigated in a multiple-case study, which consisted of two phases. In phase I the students' well-being along with the perceived levels of control, support, and demand for each individual student during their study were identified. These results were used in phase II, where the usefulness of the presented model was evaluated. The study was performed at the end of the academic year 2009/2010 in two institutions: Tampere University of Applied Sciences, School of Health Care, Finland (institution 1); and the University of Primorska, Faculty of Health Sciences, Slovenia (institution 2). Participants of the study were nursing graduates who finished their studies in 2009/2010 and the Vice-Deans for education of both institutions. The final sample included 83 students in institution 1 and 79 students in institution 2. The case study was combined with a survey (phase I) and an interview (phase II). Although the students' well-being in these two institutions was different, most students of both institutions perceived their studies as low strain, placid, and only some of the students in both institutions had a high risk of malaise. The Vice-Deans for education of both institutions confirmed that the application of the Job-Demand-Control-Support model provided relevant information on the nursing students' well-being, which helped in planning improved nursing study programmes. This study demonstrated that the Job-Demand-Control-Support model is appropriate for estimating undergraduate nursing students' well-being. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed Central

Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T.

2015-01-01

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 effects might also indicate that the methodological approach of shifting cortical asymmetry by means of bilateral tDCS protocols has failed. PMID:26161664

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

PubMed

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

2017-03-01

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

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

PubMed

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

2015-01-01

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

Bantam System Technology Project

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

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

PubMed

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

2010-04-01

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

Extending the limits of force endurance: Stimulation of the motor or the frontal cortex?

PubMed

Radel, Rémi; Tempest, Gavin; Denis, Gauthier; Besson, Pierre; Zory, Raphael

2017-12-01

Previous findings indicate that facilitation of primary motor cortex (PMC) activity using trans-cranial direct current stimulation (tDCS) could improve resistance to physical fatigue. However, studies have failed to consistently replicate these results. Using non-focal-tDCS during a fatiguing task, recent work showed no enhancement of corticospinal excitability of the PMC despite a longer endurance time and suggested that contamination in other brain regions involved in motor command may have occurred. In accordance with recent evidence supporting the role of the prefrontal cortex (PFC) in exercise maintenance, this double-blind sham-controlled crossover study (N = 22) compared the effect of high definition (HD)-tDCS of the PMC or the PFC on endurance time of a sustained contraction task of the elbow flexor. Brain activity was monitored using near infrared spectroscopy (NIRS) to measure the neurovascular response elicited by HD-tDCS. Electromyography (EMG) and force obtained during maximal voluntary and evoked contractions were assessed before and after the contraction task to explore the effect of brain stimulation on peripheral and central fatigue. While the stimulation affected the brain response in the PFC during the contraction task, no effects of the stimulation were observed on endurance time or fatigue indices. These results are discussed in relation to the neurocognitive models of physical effort. Copyright © 2017 Elsevier Ltd. All rights reserved.

The multiple-function multi-input/multi-output digital controller system for the AFW wind-tunnel model

NASA Technical Reports Server (NTRS)

Hoadley, Sherwood T.; Mcgraw, Sandra M.

1992-01-01

A real time multiple-function digital controller system was developed for the Active Flexible Wing (AFW) Program. The digital controller system (DCS) allowed simultaneous execution of two control laws: flutter suppression and either roll trim or a rolling maneuver load control. The DCS operated within, but independently of, a slower host operating system environment, at regulated speeds up to 200 Hz. It also coordinated the acquisition, storage, and transfer of data for near real time controller performance evaluation and both open- and closed-loop plant estimation. It synchronized the operation of four different processing units, allowing flexibility in the number, form, functionality, and order of control laws, and variability in the selection of the sensors and actuators employed. Most importantly, the DCS allowed for the successful demonstration of active flutter suppression to conditions approximately 26 percent (in dynamic pressure) above the open-loop boundary in cases when the model was fixed in roll and up to 23 percent when it was free to roll. Aggressive roll maneuvers with load control were achieved above the flutter boundary. The purpose here is to present the development, validation, and wind tunnel testing of this multiple-function digital controller system.

System Control for the Transitional DCS. Appendices.

DTIC Science & Technology

1978-12-01

the deployment of the AN/TTC-39 circuit switch. This is a hybrid analog/digital switch providing the following services: o Non- secure analog telephone...service. o Non- secure 16 Kb/s digital telephone service. o Secure 16 Kb/s digital telephone service with automatic key distribution and end to end... security . o Analog circuits to support current inventory 50 Kb/sec and 9.6 Kb/sec secure digital communications. In the deployment model for this study

No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults

PubMed Central

Külzow, Nadine; Cavalcanti de Sousa, Angelica Vieira; Cesarz, Magda; Hanke, Julie-Marie; Günsberg, Alida; Harder, Solvejg; Koblitz, Swantje; Grittner, Ulrike; Flöel, Agnes

2018-01-01

Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and a non-optimal timing of atDCS between sessions might have masked beneficial effects and should be more systematically addressed in future studies. PMID:29375290

The Gene Expression Profile of CD11c+CD8α− Dendritic Cells in the Pre-Diabetic Pancreas of the NOD Mouse

PubMed Central

Beumer, Wouter; Welzen-Coppens, Jojanneke M. C.; van Helden-Meeuwsen, Cornelia G.; Gibney, Sinead M.; Drexhage, Hemmo A.; Versnel, Marjan A.

2014-01-01

Two major dendritic cell (DC) subsets have been described in the pancreas of mice: The CD11c+CD8α− DCs (strong CD4+ T cell proliferation inducers) and the CD8α+CD103+ DCs (T cell apoptosis inducers). Here we analyzed the larger subset of CD11c+CD8α− DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR) to elucidate abnormalities in underlying gene expression networks. CD11c+CD8α− DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c+CD8α− DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24) was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+CD8α− DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhanced up-regulation of inflammatory genes was supported by the in vitro cytokine production profile of the DCs. In conclusion, our data show that NOD pancreatic CD11c+CD8α− DCs show various deficiencies in steady state, while hyperreactive when encountering a danger signal such as LPS. PMID:25166904

Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of Consciousness: Combined Behavioral and Event-Related Potential Evidence.

PubMed

Zhang, Ye; Song, Weiqun; Du, Jubao; Huo, Su; Shan, Guixiang; Li, Ran

2017-01-01

The electrophysiological evidence supporting the therapeutic efficacy of multiple transcranial direct current stimulation (tDCS) sessions on consciousness improvement in patients with prolonged disorders of consciousness (DOCs) has not been firmly established. To assess the effects of repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS-R) score and event-related potential (ERP). Using a sham-controlled randomized double-blind design, 26 patients were randomly assigned to either a real [five vegetative state (VS) and eight minimally conscious state (MCS) patients] or sham (six VS and seven MCS patients) stimulation group. The patients in the real stimulation group underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 10 consecutive working days. The CRS-R score and P300 amplitude and latency in a hierarchical cognitive assessment were recorded to evaluate the consciousness level before tDCS and immediately after the 20 sessions. The intra-group CRS-R analysis revealed a clinically significant improvement in the MCS patients in the real stimulation group. The inter-group CRS-R analysis showed a significant difference in CRS-R between VS and MCS patients at baseline in both the real and sham stimulation groups. The intra-group ERP analysis revealed a significant increase in P300 amplitude after tDCS in the MCS patients in the real stimulation group, but no significant differences in P300 latency. For the inter-group ERP analysis, we observed significant differences regarding the presence of P300 at baseline between the VS and MCS patients in both groups. The repeated anodal tDCS of the left DLPFC could produce clinically significant improvements in MCS patients. The observed tDCS-related consciousness improvements might be related to improvements in attention resource allocation (reflected by the P300 amplitude). The findings support the use of tDCS in clinical practice and ERP might serve as an efficient electrophysiological assessment tool in patients with DOCs.

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

PubMed

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

2012-09-01

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

Using OPC technology to support the study of advanced process control.

PubMed

Mahmoud, Magdi S; Sabih, Muhammad; Elshafei, Moustafa

2015-03-01

OPC, originally the Object Linking and Embedding (OLE) for Process Control, brings a broad communication opportunity between different kinds of control systems. This paper investigates the use of OPC technology for the study of distributed control systems (DCS) as a cost effective and flexible research tool for the development and testing of advanced process control (APC) techniques in university research centers. Co-Simulation environment based on Matlab, LabVIEW and TCP/IP network is presented here. Several implementation issues and OPC based client/server control application have been addressed for TCP/IP network. A nonlinear boiler model is simulated as OPC server and OPC client is used for closed loop model identification, and to design a Model Predictive Controller. The MPC is able to control the NOx emissions in addition to drum water level and steam pressure. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-10-24

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

Can Transcranial Direct Current Stimulation Augment Extinction of Conditioned Fear?

PubMed Central

van ’t Wout, Mascha; Mariano, Timothy Y.; Garnaat, Sarah L.; Reddy, Madhavi K.; Rasmussen, Steven A.; Greenberg, Benjamin D.

2016-01-01

Background Exposure-based therapy parallels extinction learning of conditioned fear. Prior research points to the ventromedial prefrontal cortex as a potential site for the consolidation of extinction learning and subsequent retention of extinction memory. Objective/hypothesis The present study aimed to evaluate whether the application of non-invasive transcranial direct current stimulation (tDCS) during extinction learning enhances late extinction and early recall in human participants. Methods Forty-four healthy volunteers completed a 2-day Pavlovian fear conditioning, extinction, and recall paradigm while skin conductance activity was continuously measured. Twenty-six participants received 2 mA anodal tDCS over EEG coordinate AF3 during extinction of a first conditioned stimulus. The remaining 18 participants received similar tDCS during extinction of a second conditioned stimulus. Sham stimulation was applied for the balance of extinction trials in both groups. Normalized skin conductance changes were analyzed using linear mixed models to evaluate effects of tDCS over late extinction and early recall trials. Results We observed a significant interaction between timing of tDCS during extinction blocks and changes in skin conductance reactivity over late extinction trials. These data indicate that tDCS was associated with accelerated late extinction learning of a second conditioned stimulus after tDCS was combined with extinction learning of a previous conditioned stimulus. No significant effects of tDCS timing were observed on early extinction recall. Conclusions Results could be explained by an anxiolytic aftereffect of tDCS and extend previous studies on tDCS-induced modulation of fear and threat related learning processes. These findings support further exploration of the clinical use of tDCS. PMID:27037186

PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity.

PubMed

Lim, Tong Seng; Chew, Valerie; Sieow, Je Lin; Goh, Siting; Yeong, Joe Poh-Sheng; Soon, Ai Ling; Ricciardi-Castagnoli, Paola

2016-03-01

Programmed death one (PD-1) is a well-established co-inhibitory regulator that suppresses proliferation and cytokine production of T cells. Despite remarkable progress in delineating the functional roles of PD-1 on T lymphocytes, little is known about the regulatory role of PD-1 expressed on myeloid cells such as dendritic cells (DCs). Here, we show that CD8 + T cells can be more potently activated to secrete IL-2 and IFNγ by PD-1-deficient DCs compared to wild-type DCs. Adoptive transfer of PD-1-deficient DCs demonstrated their superior capabilities in inducing antigen-specific CD8 + T cell proliferation in vivo . In addition, we provide first evidence demonstrating the existence of peripheral blood DCs and CD11c + tumor-infiltrating myeloid cells that co-express PD-1 in patients with hepatocellular carcinoma (HCC). The existence of PD-1-expressing HCC-infiltrating DCs (HIDCs) was further supported in a mouse model of HCC. Intratumoral transfer of PD-1-deficient DCs rendered recipient mice resistant to the growth of HCC by promoting tumor-infiltrating CD8 + effector T cells to secrete perforin and granzyme B. This novel finding provides a deeper understanding of the role of PD-1 in immune regulation and has significant implications for cancer immunotherapies targeting PD-1.

PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity

PubMed Central

Lim, Tong Seng; Chew, Valerie; Sieow, Je Lin; Goh, Siting; Yeong, Joe Poh-Sheng; Soon, Ai Ling; Ricciardi-Castagnoli, Paola

2016-01-01

ABSTRACT Programmed death one (PD-1) is a well-established co-inhibitory regulator that suppresses proliferation and cytokine production of T cells. Despite remarkable progress in delineating the functional roles of PD-1 on T lymphocytes, little is known about the regulatory role of PD-1 expressed on myeloid cells such as dendritic cells (DCs). Here, we show that CD8+ T cells can be more potently activated to secrete IL-2 and IFNγ by PD-1-deficient DCs compared to wild-type DCs. Adoptive transfer of PD-1-deficient DCs demonstrated their superior capabilities in inducing antigen-specific CD8+ T cell proliferation in vivo. In addition, we provide first evidence demonstrating the existence of peripheral blood DCs and CD11c+ tumor-infiltrating myeloid cells that co-express PD-1 in patients with hepatocellular carcinoma (HCC). The existence of PD-1-expressing HCC-infiltrating DCs (HIDCs) was further supported in a mouse model of HCC. Intratumoral transfer of PD-1-deficient DCs rendered recipient mice resistant to the growth of HCC by promoting tumor-infiltrating CD8+ effector T cells to secrete perforin and granzyme B. This novel finding provides a deeper understanding of the role of PD-1 in immune regulation and has significant implications for cancer immunotherapies targeting PD-1. PMID:27141339

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

PubMed

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

2017-08-01

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

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

PubMed

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

2016-10-01

To investigate the effect of transcranial direct current stimulation (tDCS) on food craving, intake, binge eating desire, and binge eating frequency in individuals with binge eating disorder (BED). N = 30 adults with BED or subthreshold BED received a 20-min 2 milliampere (mA) session of tDCS targeting the dorsolateral prefrontal cortex (DLPFC; anode right/cathode left) and a sham session. Food image ratings assessed food craving, a laboratory eating test assessed food intake, and an electronic diary recorded binge variables. tDCS versus sham decreased craving for sweets, savory proteins, and an all-foods category, with strongest reductions in men (p < 0.05). tDCS also decreased total and preferred food intake by 11 and 17.5%, regardless of sex (p < 0.05), and reduced desire to binge eat in men on the day of real tDCS administration (p < 0.05). The reductions in craving and food intake were predicted by eating less frequently for reward motives, and greater intent to restrict calories, respectively. This proof of concept study is the first to find ameliorating effects of tDCS in BED. Stimulation of the right DLPFC suggests that enhanced cognitive control and/or decreased need for reward may be possible functional mechanisms. The results support investigation of repeated tDCS as a safe and noninvasive treatment adjunct for BED. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:930-936). © 2016 Wiley Periodicals, Inc.

Effects of transcranial direct current stimulation for treating depression: A modeling study.

PubMed

Csifcsák, Gábor; Boayue, Nya Mehnwolo; Puonti, Oula; Thielscher, Axel; Mittner, Matthias

2018-07-01

Transcranial direct current stimulation (tDCS) above the left dorsolateral prefrontal cortex (lDLPFC) has been widely used to improve symptoms of major depressive disorder (MDD). However, the effects of different stimulation protocols in the entire frontal lobe have not been investigated in a large sample including patient data. We used 38 head models created from structural magnetic resonance imaging data of 19 healthy adults and 19 MDD patients and applied computational modeling to simulate the spatial distribution of tDCS-induced electric fields (EFs) in 20 frontal regions. We evaluated effects of seven bipolar and two multi-electrode 4 × 1 tDCS protocols. For bipolar montages, EFs were of comparable strength in the lDLPFC and in the medial prefrontal cortex (MPFC). Depending on stimulation parameters, EF cortical maps varied to a considerable degree, but were found to be similar in controls and patients. 4 × 1 montages produced more localized, albeit weaker effects. White matter anisotropy was not modeled. The relationship between EF strength and clinical response to tDCS could not be evaluated. In addition to lDLPFC stimulation, excitability changes in the MPFC should also be considered as a potential mechanism underlying clinical efficacy of bipolar montages. MDD-associated anatomical variations are not likely to substantially influence current flow. Individual modeling of tDCS protocols can substantially improve cortical targeting. We make recommendations for future research to explicitly test the contribution of lDLPFC vs. MPFC stimulation to therapeutic outcomes of tDCS in this disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-11-01

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

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

PubMed

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

PubMed Central

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P.; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M.; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders. PMID:28861085

Generation of transgenic mice expressing EGFP protein fused to NP68 MHC class I epitope using lentivirus vectors.

PubMed

Tomkowiak, Martine; Ghittoni, Raffaella; Teixeira, Marie; Blanquier, Bariza; Szécsi, Judit; Nègre, Didier; Aubert, Denise; Coupet, Charles-Antoine; Brunner, Molly; Verhoeyen, Els; Thoumas, Jean-Louis; Cosset, François-Loïc; Leverrier, Yann; Marvel, Jacqueline

2013-03-01

Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. Considerable progress in deciphering the mechanisms controlling the activation or deletion of T cells has been made by using T cell receptor (TCR) transgenic mice. One such model is the F5 model in which CD8 T cells express a TCR specific for an epitope derived from the influenza NP68 protein. Our aim was to create transgenic mouse models expressing constitutively the NP68 epitope fused to enhanced green fluorescent protein (EGFP) in order to assess unambiguously the relative levels of NP68 epitope expressed by single cells. We used a lentiviral-based approach to generate two independent transgenic mouse strains expressing the fusion protein EGFP-NP68 under the control of CAG (CMV immediate early enhancer and the chicken β-actin promoter) or spleen focus-forming virus (SFFV) promoters. Analysis of the pattern of EGFP expression in the hematopoietic compartment showed that CAG and SFFV promoters are differentially regulated during T cell development. However, both promoters drove high EGFP-NP68 expression in dendritic cells (pDCs, CD8α(+) cDCs, and CD8α(-) cDCs) from spleen or generated in vitro following differentiation from bone-marrow progenitors. NP68 epitope was properly processed and successfully presented by dendritic cells (DCs) by direct presentation and cross-presentation to F5 CD8 T cells. The models presented here are valuable tools to investigate the priming of F5 CD8 T cells by different subsets of DCs. Copyright © 2013 Wiley Periodicals, Inc.

Non-invasive brain stimulation and computational models in post-stroke aphasic patients: single session of transcranial magnetic stimulation and transcranial direct current stimulation. A randomized clinical trial.

PubMed

Santos, Michele Devido Dos; Cavenaghi, Vitor Breseghello; Mac-Kay, Ana Paula Machado Goyano; Serafim, Vitor; Venturi, Alexandre; Truong, Dennis Quangvinh; Huang, Yu; Boggio, Paulo Sérgio; Fregni, Felipe; Simis, Marcel; Bikson, Marom; Gagliardi, Rubens José

2017-01-01

Patients undergoing the same neuromodulation protocol may present different responses. Computational models may help in understanding such differences. The aims of this study were, firstly, to compare the performance of aphasic patients in naming tasks before and after one session of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and sham, and analyze the results between these neuromodulation techniques; and secondly, through computational model on the cortex and surrounding tissues, to assess current flow distribution and responses among patients who received tDCS and presented different levels of results from naming tasks. Prospective, descriptive, qualitative and quantitative, double blind, randomized and placebo-controlled study conducted at Faculdade de Ciências Médicas da Santa Casa de São Paulo. Patients with aphasia received one session of tDCS, TMS or sham stimulation. The time taken to name pictures and the response time were evaluated before and after neuromodulation. Selected patients from the first intervention underwent a computational model stimulation procedure that simulated tDCS. The results did not indicate any statistically significant differences from before to after the stimulation.The computational models showed different current flow distributions. The present study did not show any statistically significant difference between tDCS, TMS and sham stimulation regarding naming tasks. The patients'responses to the computational model showed different patterns of current distribution.

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

PubMed Central

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2013-01-01

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

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

PubMed

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.

Models for predicting turnover of residential aged care nurses: a structural equation modelling analysis of secondary data.

PubMed

Gao, Fengsong; Newcombe, Peter; Tilse, Cheryl; Wilson, Jill; Tuckett, Anthony

2014-09-01

Nurse turnover in the residential aged care industry is a pressing issue. Researchers have shown ongoing interest in exploring how the factors that are amendable to change in aged care policy, regulation and funding and in organizational procedures (e.g. job demands, coping resources and psychological health of nurses) impact on turnover. However, the findings are mixed. This study tested two theoretical models of turnover to examine the structural relationships among job demands, coping resources, psychological health and turnover of residential aged care nurses. Although many previous studies operationalized turnover as intention to leave, the present study investigated actual turnover by following up with the same individuals over time, and thus provided more accurate predictive models of turnover behaviour. The sample, 239 Australian residential aged care nurses, came from the Nurses and Midwives e-cohort Study. Job demands, coping resources, and psychological health were measured using standardized instruments. Structural equation modelling was used to test the measurement and structural models. Controlling for a number of workforce and individual characteristics, coping resources (measured by job control, supervisor support, and co-worker support) were negatively and directly associated with turnover. Additionally, the findings supported the Job Demand-Control-Support model in that higher coping resources and lower job demands (indicated by psychological demands, physical demands, and effort) were related to better psychological health (measured by vitality, social functioning, role emotional, and mental health), and higher job demands were related to lower coping resources. Findings suggest that aged care policy makers and service providers might consider increasing coping resources available to nurses and minimizing job demands of care work to reduce turnover and improve nurses' psychological health. Moreover, findings from this Australian study may provide valuable practical and policy implications for other developed countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-09-01

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

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

PubMed

Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcranial direct current stimulation improves clinical symptoms in adolescents with attention deficit hyperactivity disorder.

PubMed

Soff, Cornelia; Sotnikova, Anna; Christiansen, Hanna; Becker, Katja; Siniatchkin, Michael

2017-01-01

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has repeatedly been shown to improve working memory. As patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in working memory that correlate with clinical symptoms, it is hypothesized that the modulation of prefrontal activity with tDCS in patients with ADHD increases performance in working memory and reduces symptoms of ADHD. To test this hypothesis, fifteen adolescents with ADHD (12-16 years old, three girls and 12 boys) were treated according to the randomized, double-blinded, sham-controlled, crossover design with either 1 mA anodal tDCS over the left dorsolateral prefrontal cortex or with the sham protocol 5 days each with a 2 weeks pause between these conditions. Anodal tDCS caused a significant reduction in clinical symptoms of inattention and impulsivity in adolescents with ADHD compared to sham stimulation. The clinical effects were supported by a significant reduction in inattention and hyperactivity in a standardized working memory test (QbTest). The described effects were more pronounced 7 days after the end of stimulation, a fact which emphasizes the long-lasting clinical and neuropsychological changes after tDCS. This study provides the first evidence that tDCS may reduce symptoms of ADHD and improve neuropsychological functioning in adolescents and points on the potential of tDCS as a form of treatment for ADHD.

Network Speech Systems Technology Program

NASA Astrophysics Data System (ADS)

Weinstein, C. J.

1980-09-01

This report documents work performed during FY 1980 on the DCA-sponsored Network Speech Systems Technology Program. The areas of work reported are: (1) communication systems studies in Demand-Assignment Multiple Access (DAMA), voice/data integration, and adaptive routing, in support of the evolving Defense Communications System (DCS) and Defense Switched Network (DSN); (2) a satellite/terrestrial integration design study including the functional design of voice and data interfaces to interconnect terrestrial and satellite network subsystems; and (3) voice-conferencing efforts dealing with support of the Secure Voice and Graphics Conferencing (SVGC) Test and Evaluation Program. Progress in definition and planning of experiments for the Experimental Integrated Switched Network (EISN) is detailed separately in an FY 80 Experiment Plan Supplement.

The Influence of Recognition and Social Support on European Health Professionals' Occupational Stress: A Demands-Control-Social Support-Recognition Bayesian Network Model

PubMed Central

Lopez-Garcia, Jose R.; Herrera, Sixto; Fontaneda, Ignacio; Báscones, Sonia Muñoz; Mariscal, Miguel A.

2017-01-01

Healthcare professionals undergo high levels of occupational stress as a result of their working conditions. Thus, the aim of this study is to develop a model that focuses on healthcare professionals so as to analyze the influence that job demands, control, social support, and recognition have on the likelihood that a worker will experience stress. The data collected correspond to 2,211 healthcare workers from 35 countries, as reported in the sixth European Working Condition Survey (EWCS). The results obtained from this study allow us to infer stress under several working condition scenarios and to identify the more relevant variables in order to reduce this stress in healthcare professionals, which is of paramount importance to managing the stress of workers in this sector. The Bayesian network proposed indicates that emotional demands have a greater influence on raising the likelihood of stress due to workload than do family demands. The results show that the support of colleagues, in general, has less effect on reducing stress than social support from superiors. Furthermore, the sensitivity analysis shows that, in high-demand and low-control situations, recognition clearly impacts stress, drastically reducing it. PMID:29250540

The Influence of Recognition and Social Support on European Health Professionals' Occupational Stress: A Demands-Control-Social Support-Recognition Bayesian Network Model.

PubMed

García-Herrero, Susana; Lopez-Garcia, Jose R; Herrera, Sixto; Fontaneda, Ignacio; Báscones, Sonia Muñoz; Mariscal, Miguel A

2017-01-01

Healthcare professionals undergo high levels of occupational stress as a result of their working conditions. Thus, the aim of this study is to develop a model that focuses on healthcare professionals so as to analyze the influence that job demands, control, social support, and recognition have on the likelihood that a worker will experience stress. The data collected correspond to 2,211 healthcare workers from 35 countries, as reported in the sixth European Working Condition Survey (EWCS). The results obtained from this study allow us to infer stress under several working condition scenarios and to identify the more relevant variables in order to reduce this stress in healthcare professionals, which is of paramount importance to managing the stress of workers in this sector. The Bayesian network proposed indicates that emotional demands have a greater influence on raising the likelihood of stress due to workload than do family demands. The results show that the support of colleagues, in general, has less effect on reducing stress than social support from superiors. Furthermore, the sensitivity analysis shows that, in high-demand and low-control situations, recognition clearly impacts stress, drastically reducing it.

Spreading Effect of tDCS in Individuals with Attention-Deficit/Hyperactivity Disorder as Shown by Functional Cortical Networks: A Randomized, Double-Blind, Sham-Controlled Trial.

PubMed

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

2015-01-01

Transcranial direct current stimulation (tDCS) is known to modulate spontaneous neural network excitability. The cognitive improvement observed in previous trials raises the potential of this technique as a possible therapeutic tool for use in attention-deficit/hyperactivity disorder (ADHD) population. However, to explore the potential of this technique as a treatment approach, the functional parameters of brain connectivity and the extent of its effects need to be more fully investigated. The aim of this study was to investigate a functional cortical network (FCN) model based on electroencephalographic activity for studying the dynamic patterns of brain connectivity modulated by tDCS and the distribution of its effects in individuals with ADHD. Sixty ADHD patients participated in a parallel, randomized, double-blind, sham-controlled trial. Individuals underwent a single session of sham or anodal tDCS at 1 mA of current intensity over the left dorsolateral prefrontal cortex for 20 min. The acute effects of stimulation on brain connectivity were assessed using the FCN model based on electroencephalography activity. Comparing the weighted node degree within groups prior to and following the intervention, a statistically significant difference was found in the electrodes located on the target and correlated areas in the active group (p < 0.05), while no statistically significant results were found in the sham group (p ≥ 0.05; paired-sample Wilcoxon signed-rank test). Anodal tDCS increased functional brain connectivity in individuals with ADHD compared to data recorded in the baseline resting state. In addition, although some studies have suggested that the effects of tDCS are selective, the present findings show that its modulatory activity spreads. Further studies need to be performed to investigate the dynamic patterns and physiological mechanisms underlying the modulatory effects of tDCS. ClinicalTrials.gov NCT01968512.

Managerial leadership is associated with employee stress, health, and sickness absence independently of the demand-control-support model.

PubMed

Westerlund, Hugo; Nyberg, Anna; Bernin, Peggy; Hyde, Martin; Oxenstierna, Gabriel; Jäppinen, Paavo; Väänänen, Ari; Theorell, Töres

2010-01-01

Research on health effects of managerial leadership has only taken established work environment factors into account to a limited extent. We therefore investigated the associations between a measure of Attentive Managerial Leadership (AML), and perceived stress, age-relative self-rated health, and sickness absence due to overstrain/fatigue, adjusting for the dimensions of the Demand-Control-Support model. Blue- and white-collar workers from Finland, Germany and Sweden employed in a multi-national forest industry company (N=12,622). Cross-sectional data on leadership and health from a company-wide survey analysed with logistic regression in different subgroups. AML was associated with perceived stress, age-relative self-rated health, and sickness absence due to overstrain/fatigue after controlling for the Demand-Control-Support model. Lack of AML was significantly associated with a high stress level in all subgroups (OR=1.68-2.67). Associations with age-relative self-rated health and sickness absence due to overstrain/fatigue were weaker, but still significant, and in the expected direction for several of the subgroups studied, suggesting an association between lack of AML and negative health consequences. The study indicates that managerial leadership is associated with employee stress, health, and sickness absence independently of the Demand-Control-Support model and should be considered in future studies of health consequences for employees, and in work environment interventions.

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

PubMed

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

2017-09-01

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

Dendritic cells infected by Ad-sh-SOCS1 enhance cytokine-induced killer (CIK) cell immunotherapeutic efficacy in cervical cancer models.

PubMed

Zheng, Yi; Hu, Bicheng; Xie, Shenggao; Chen, Xiaofan; Hu, Yuqian; Chen, Wanping; Li, Shanshan; Hu, Bo

2017-05-01

Cervical cancer constitutes a major problem in women's health worldwide, but the efficacy of the standard therapy is unsatisfactory. Cytokine-induced killer (CIK) cells exhibit antitumor activity against a variety of malignancies in preclinical models and have proven safe and effective in clinical trials. However, current CIK therapy has limitations and needs to be improved to meet the clinical requirements. The aim of this study was to investigate whether suppressing the expression of cytokine signaling 1 (SOCS1) in dendritic cells (DCs) can shorten in vitro CIK culture time and improve its antitumor efficacy. DCs were pre-cultured for 3 days before infected with adenovirus-mediated-SOCS1 short hairpin RNA (Ad-sh-SOCS1) and pulsed with CTL epitope peptides E7. The DCs infected by Ad-sh-SOCS1 (gmDCs) and CIKs were then co-cultured for 5 or 9 days, and CIK proliferation and antitumor activity were evaluated both in vitro and in vivo. Our data show that gmDCs significantly stimulated the expansion of co-cultured CIKs and increased the secretion of interferon-γ and interleukin-12. Moreover, gmDCs-activated CIKs showed higher cytotoxic activity against TC-1 cells expressing HPV16E6 and E7. Our in vivo study showed that the mice infused with gmDCs-activated CIKs on day 10 had an increased survival rate and prolonged survival time compared with the controls. Taken together, these results indicate that DCs modified by adenovirus-mediated SOCS1 silencing can promote CIKs expansion and enhance the efficacy of antitumor immunotherapy both in vitro and in vivo, which represents an effective therapeutic approach for cervical cancer and other tumors. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-06-21

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability-enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm(2)) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring's diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation ([Formula: see text] · (σ [Formula: see text] V)  =  0) was solved for cortical electric field, which was interpreted using physiological assumptions to correlate with stimulation and modulation. Cortical field intensity was predicted to increase with increasing ring diameter at the cost of focality while uni-directionality decreased. Additional surrounding ring electrodes increased uni-directionality while lowering cortical field intensity and increasing focality; though, this effect saturated and more than 4 surround electrode would not be justified. Using a range of concentric HD-tDCS montages, we showed that cortical region of influence can be controlled while balancing other design factors such as intensity at the target and uni-directionality. Furthermore, the evaluated concentric HD-tDCS approaches can provide categorical improvements in targeting compared to conventional tDCS. Hypothesis driven clinical trials, based on specific target engagement, would benefit by this more precise method of stimulation that could avoid potentially confounding brain regions.

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

PubMed

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

2017-07-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2017-09-01

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

D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity

PubMed Central

Goff, Donald C.

2017-01-01

Background Dysregulation of N-methyl D-aspartate (NMDA) receptor signaling is strongly implicated in schizophrenia. Based on the ketamine model of NMDA receptor hypoactivity, therapeutic approaches designed to maintain a sustained increase in agonist activity at the glycine site of the NMDA receptor have produced promising, although inconsistent, efficacy for negative symptoms. Methods A review of the published literature on D-cycloserine (DCS) pharmacology in animal models and in clinical studies was performed. Findings relevant to DCS effects on memory and plasticity and their potential clinical application to schizophrenia were summarized. Results Studies in animals and clinical trials in patients with anxiety disorders have demonstrated that single or intermittent dosing with DCS enhances memory consolidation. Preliminary trials in patients with schizophrenia suggest that intermittent dosing with DCS may produce persistent improvement of negative symptoms and enhance learning when combined with cognitive behavioral therapy for delusions or with cognitive remediation. The pharmacology of DCS is complex, since it acts as a “super agonist” at NMDA receptors containing GluN2C subunits and, under certain conditions, it may act as an antagonist at NMDA receptors containing GluN2B subunits. Conclusions There are preliminary findings that support a role for D-cycloserine in schizophrenia as a strategy to enhance neuroplasticity and memory. However, additional studies with DCS are needed to confirm these findings. In addition, clinical trials with positive and negative allosteric modulators with greater specificity for NMDA receptor subtypes are needed to identify the optimal strategy for enhancing neuroplasticity in schizophrenia. PMID:26915421

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

PubMed

Parikh, Pranav J; Cole, Kelly J

2015-01-01

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

A rat model of chronic moderate alcohol consumption and risk of decompression sickness.

PubMed

Buzzacott, Peter; Mazur, Aleksandra; Wang, Qiong; Lambrechts, Kate; Theron, Michael; Guerrero, François

2015-06-01

This study aimed to establish if chronic, moderate, pre-dive alcohol consumption had any affect upon susceptibility to decompression sickness (DCS) in rats. A treatment group of 15 rats were given water containing 12 mL ·L ⁻¹ of ethanol for four weeks. Controls (n = 15) were given water. Both groups were compressed with air to 1,000 kPa, followed by staged decompression. An additional 30 control rats from a similar previous experiment were added, raising the control-treatment ratio to 3:1. Rats in the treatment group consumed the equivalent of an 80 kg man drinking 2 L of 5 % alcohol by volume beer per day, which is three times the recommended daily limit for men. Overall, comparing the treatment group with the combined control groups neither weight (P = 0.23) nor alcohol consumption (P = 0.69) were associated with DCS. We observed that chronic, moderate alcohol consumption prior to compression was neither prophylactic nor deleterious for DCS in young, male rats.

How Changes in Psychosocial Job Characteristics Impact Burnout in Nurses: A Longitudinal Analysis.

PubMed

Pisanti, Renato; van der Doef, Margot; Maes, Stan; Meier, Laurenz Linus; Lazzari, David; Violani, Cristiano

2016-01-01

The main aim of this longitudinal study was to test the Job Demand-Control-Support (JDCS) model and to analyze whether changes in psychosocial job characteristics are related to (changes in) burnout. Previous studies on the effects of JDCS variables on burnout dimensions have indicated that the iso-strain hypothesis (i.e., high job demands, low control, and low support additively predict high stress reactions) and the buffer hypotheses (i.e., high job control and/or social support is expected to moderate the negative impact of high demands on stress reactions) have hardly been examined concurrently in a longitudinal design; and that the effects of changes of psychosocial job variables on burnout dimensions have hardly been analyzed. This two wave study was carried out over a period of 14 months in a sample of 217 Italian nurses. Hierarchical regression analyses were used to test the cross lagged main and interactive effects of JDCS variables, and to analyse the across-time effects of changes in JDCS dimensions on burnout variables. The Time 1 job characteristics explained 2-8% of the variance in the Time 2 burnout dimensions, but no support for the additive, or the buffer hypothesis of the JDCS model was found. Changes in job characteristics explained an additional 3-20% of variance in the Time 2 burnout dimensions. Specifically, high levels of emotional exhaustion at Time 2 were explained by high levels of social support at Time 1, and unfavorable changes in demands, control, and support over time; high depersonalization at Time 2 was explained by high social support at time 1 and by an increase in demands over time; and high personal accomplishment at Time 2 was predicted by high demands, high control, interactive effect demands × control × social support, at Time 1, and by a decrease in demands over time. No reversed effects of burnout on work characteristics have been found. Our findings suggest that the work environment is subject to changes: the majority of employees experienced considerable changes in all job conditions over time. These changes impacted employee burnout. Limitations and implications of the study are discussed.

How Changes in Psychosocial Job Characteristics Impact Burnout in Nurses: A Longitudinal Analysis

PubMed Central

Pisanti, Renato; van der Doef, Margot; Maes, Stan; Meier, Laurenz Linus; Lazzari, David; Violani, Cristiano

2016-01-01

Aims: The main aim of this longitudinal study was to test the Job Demand-Control-Support (JDCS) model and to analyze whether changes in psychosocial job characteristics are related to (changes in) burnout. Background: Previous studies on the effects of JDCS variables on burnout dimensions have indicated that the iso-strain hypothesis (i.e., high job demands, low control, and low support additively predict high stress reactions) and the buffer hypotheses (i.e., high job control and/or social support is expected to moderate the negative impact of high demands on stress reactions) have hardly been examined concurrently in a longitudinal design; and that the effects of changes of psychosocial job variables on burnout dimensions have hardly been analyzed. Design: This two wave study was carried out over a period of 14 months in a sample of 217 Italian nurses. Method: Hierarchical regression analyses were used to test the cross lagged main and interactive effects of JDCS variables, and to analyse the across-time effects of changes in JDCS dimensions on burnout variables. Results: The Time 1 job characteristics explained 2–8% of the variance in the Time 2 burnout dimensions, but no support for the additive, or the buffer hypothesis of the JDCS model was found. Changes in job characteristics explained an additional 3–20% of variance in the Time 2 burnout dimensions. Specifically, high levels of emotional exhaustion at Time 2 were explained by high levels of social support at Time 1, and unfavorable changes in demands, control, and support over time; high depersonalization at Time 2 was explained by high social support at time 1 and by an increase in demands over time; and high personal accomplishment at Time 2 was predicted by high demands, high control, interactive effect demands × control × social support, at Time 1, and by a decrease in demands over time. No reversed effects of burnout on work characteristics have been found. Conclusion: Our findings suggest that the work environment is subject to changes: the majority of employees experienced considerable changes in all job conditions over time. These changes impacted employee burnout. Limitations and implications of the study are discussed. PMID:27507952

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

PubMed

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

2017-09-13

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

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

PubMed Central

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. PMID:27031726

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

PubMed

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

2010-07-01

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

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

PubMed

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

2016-10-01

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

Evidence for local dendritic cell activation in pulmonary sarcoidosis

PubMed Central

2012-01-01

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

An experience sampling study of learning, affect, and the demands control support model.

PubMed

Daniels, Kevin; Boocock, Grahame; Glover, Jane; Holland, Julie; Hartley, Ruth

2009-07-01

The demands control support model (R. A. Karasek & T. Theorell, 1990) indicates that job control and social support enable workers to engage in problem solving. In turn, problem solving is thought to influence learning and well-being (e.g., anxious affect, activated pleasant affect). Two samples (N = 78, N = 106) provided data up to 4 times per day for up to 5 working days. The extent to which job control was used for problem solving was assessed by measuring the extent to which participants changed aspects of their work activities to solve problems. The extent to which social support was used to solve problems was assessed by measuring the extent to which participants discussed problems to solve problems. Learning mediated the relationship between changing aspects of work activities to solve problems and activated pleasant affect. Learning also mediated the relationship between discussing problems to solve problems and activated pleasant affect. The findings indicated that how individuals use control and support to respond to problem-solving demands is associated with organizational and individual phenomena, such as learning and affective well-being.

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

PubMed

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

2017-10-01

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

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

PubMed

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.

Porphyromonas gingivalis-dendritic cell interactions: consequences for coronary artery disease.

PubMed

Zeituni, Amir E; Carrion, Julio; Cutler, Christopher W

2010-12-21

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Iso-risk air no decompression limits after scoring marginal decompression sickness cases as non-events.

PubMed

Murphy, F Gregory; Swingler, Ashleigh J; Gerth, Wayne A; Howle, Laurens E

2018-01-01

Decompression sickness (DCS) in humans is associated with reductions in ambient pressure that occur during diving, aviation, or certain manned spaceflight operations. Its signs and symptoms can include, but are not limited to, joint pain, radiating abdominal pain, paresthesia, dyspnea, general malaise, cognitive dysfunction, cardiopulmonary dysfunction, and death. Probabilistic models of DCS allow the probability of DCS incidence and time of occurrence during or after a given hyperbaric or hypobaric exposure to be predicted based on how the gas contents or gas bubble volumes vary in hypothetical tissue compartments during the exposure. These models are calibrated using data containing the pressure and respired gas histories of actual exposures, some of which resulted in DCS, some of which did not, and others in which the diagnosis of DCS was not clear. The latter are referred to as marginal DCS cases. In earlier works, a marginal DCS event was typically weighted as 0.1, with a full DCS event being weighted as 1.0, and a non-event being weighted as 0.0. Recent work has shown that marginal DCS events should be weighted as 0.0 when calibrating gas content models. We confirm this indication in the present work by showing that such models have improved performance when calibrated to data with marginal DCS events coded as non-events. Further, we investigate the ramifications of derating marginal events on model-prescribed air diving no-stop limits. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2010-11-01

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

Information modeling system for blast furnace control

NASA Astrophysics Data System (ADS)

Spirin, N. A.; Gileva, L. Y.; Lavrov, V. V.

2016-09-01

Modern Iron & Steel Works as a rule are equipped with powerful distributed control systems (DCS) and databases. Implementation of DSC system solves the problem of storage, control, protection, entry, editing and retrieving of information as well as generation of required reporting data. The most advanced and promising approach is to use decision support information technologies based on a complex of mathematical models. The model decision support system for control of blast furnace smelting is designed and operated. The basis of the model system is a complex of mathematical models created using the principle of natural mathematical modeling. This principle provides for construction of mathematical models of two levels. The first level model is a basic state model which makes it possible to assess the vector of system parameters using field data and blast furnace operation results. It is also used to calculate the adjustment (adaptation) coefficients of the predictive block of the system. The second-level model is a predictive model designed to assess the design parameters of the blast furnace process when there are changes in melting conditions relative to its current state. Tasks for which software is developed are described. Characteristics of the main subsystems of the blast furnace process as an object of modeling and control - thermal state of the furnace, blast, gas dynamic and slag conditions of blast furnace smelting - are presented.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

PubMed Central

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

2017-01-01

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

Probabilistic pharmacokinetic models of decompression sickness in humans, part 1: Coupled perfusion-limited compartments.

PubMed

Murphy, F Gregory; Hada, Ethan A; Doolette, David J; Howle, Laurens E

2017-07-01

Decompression sickness (DCS) is a disease caused by gas bubbles forming in body tissues following a reduction in ambient pressure, such as occurs in scuba diving. Probabilistic models for quantifying the risk of DCS are typically composed of a collection of independent, perfusion-limited theoretical tissue compartments which describe gas content or bubble volume within these compartments. It has been previously shown that 'pharmacokinetic' gas content models, with compartments coupled in series, show promise as predictors of the incidence of DCS. The mechanism of coupling can be through perfusion or diffusion. This work examines the application of five novel pharmacokinetic structures with compartments coupled by perfusion to the prediction of the probability and time of onset of DCS in humans. We optimize these models against a training set of human dive trial data consisting of 4335 exposures with 223 DCS cases. Further, we examine the extrapolation quality of the models on an additional set of human dive trial data consisting of 3140 exposures with 147 DCS cases. We find that pharmacokinetic models describe the incidence of DCS for single air bounce dives better than a single-compartment, perfusion-limited model. We further find the U.S. Navy LEM-NMRI98 is a better predictor of DCS risk for the entire training set than any of our pharmacokinetic models. However, one of the pharmacokinetic models we consider, the CS2T3 model, is a better predictor of DCS risk for single air bounce dives and oxygen decompression dives. Additionally, we find that LEM-NMRI98 outperforms CS2T3 on the extrapolation data. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

Vallée, Nicolas; Ignatescu, Mihaela; Bourdon, Lionel

2011-01-01

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

A Distributed Control System Prototyping Environment to Support Control Room Modernization

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

Lew, Roger Thomas; Boring, Ronald Laurids; Ulrich, Thomas Anthony

Operators of critical processes, such as nuclear power production, must contend with highly complex systems, procedures, and regulations. Developing human-machine interfaces (HMIs) that better support operators is a high priority for ensuring the safe and reliable operation of critical processes. Human factors engineering (HFE) provides a rich and mature set of tools for evaluating the performance of HMIs, however the set of tools for developing and designing HMIs is still in its infancy. Here we propose a rapid prototyping approach for integrating proposed HMIs into their native environments before a design is finalized. This approach allows researchers and developers tomore » test design ideas and eliminate design flaws prior to fully developing the new system. We illustrate this approach with four prototype designs developed using Microsoft’s Windows Presentation Foundation (WPF). One example is integrated into a microworld environment to test the functionality of the design and identify the optimal level of automation for a new system in a nuclear power plant. The other three examples are integrated into a full-scale, glasstop digital simulator of a nuclear power plant. One example demonstrates the capabilities of next generation control concepts; another aims to expand the current state of the art; lastly, an HMI prototype was developed as a test platform for a new control system currently in development at U.S. nuclear power plants. WPF possesses several characteristics that make it well suited to HMI design. It provides a tremendous amount of flexibility, agility, robustness, and extensibility. Distributed control system (DCS) specific environments tend to focus on the safety and reliability requirements for real-world interfaces and consequently have less emphasis on providing functionality to support novel interaction paradigms. Because of WPF’s large user-base, Microsoft can provide an extremely mature tool. Within process control applications,WPF is platform independent and can communicate with popular full-scope process control simulator vendor plant models and DCS platforms.« less

Is Motor Learning Mediated by tDCS Intensity?

PubMed Central

van den Berg, Femke E.; Nitsche, Michael A.; Thijs, Herbert; Wenderoth, Nicole; Meesen, Raf L. J.

2013-01-01

Although tDCS has been shown to improve motor learning, previous studies reported rather small effects. Since physiological effects of tDCS depend on intensity, the present study evaluated this parameter in order to enhance the effect of tDCS on skill acquisition. The effect of different stimulation intensities of anodal tDCS (atDCS) was investigated in a double blind, sham controlled crossover design. In each condition, thirteen healthy subjects were instructed to perform a unimanual motor (sequence) learning task. Our results showed (1) a significant increase in the slope of the learning curve and (2) a significant improvement in motor performance at retention for 1.5 mA atDCS as compared to sham tDCS. No significant differences were reported between 1 mA atDCS and sham tDCS; and between 1.5 mA atDCS and 1 mA atDCS. PMID:23826272

Job Demands-Control-Support model and employee safety performance.

PubMed

Turner, Nick; Stride, Chris B; Carter, Angela J; McCaughey, Deirdre; Carroll, Anthony E

2012-03-01

The aim of this study was to explore whether work characteristics (job demands, job control, social support) comprising Karasek and Theorell's (1990) Job Demands-Control-Support framework predict employee safety performance (safety compliance and safety participation; Neal and Griffin, 2006). We used cross-sectional data of self-reported work characteristics and employee safety performance from 280 healthcare staff (doctors, nurses, and administrative staff) from Emergency Departments of seven hospitals in the United Kingdom. We analyzed these data using a structural equation model that simultaneously regressed safety compliance and safety participation on the main effects of each of the aforementioned work characteristics, their two-way interactions, and the three-way interaction among them, while controlling for demographic, occupational, and organizational characteristics. Social support was positively related to safety compliance, and both job control and the two-way interaction between job control and social support were positively related to safety participation. How work design is related to employee safety performance remains an important area for research and provides insight into how organizations can improve workplace safety. The current findings emphasize the importance of the co-worker in promoting both safety compliance and safety participation. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression

PubMed Central

Verma, Vivek; Kim, Young; Lee, Min-Cheol; Lee, Jae-Tae; Cho, Sunghoon; Park, In-Kyu; Min, Jung Joon; Lee, Je Jung; Lee, Shee Eun; Rhee, Joon Haeng

2016-01-01

Dendritic cell (DC) based anti-cancer immunotherapy is well tolerated in patients with advanced cancers. However, the clinical responses seen after adoptive DC therapy have been suboptimal. Several factors including scarce DC numbers in tumors and immunosuppressive tumor microenvironments contribute to the inefficacy of DCs as cellular vaccines. Hence DC based vaccines can benefit from novel methods of cell delivery that would prevent the direct exposure of immune cells to suppressive tumor microenvironments. Here we evaluated the ability of DCs harbored in biocompatible scaffolds (referred to as biomatrix entrapped DCs; beDCs) in activating specific anti-tumor immune responses against primary and post-surgery secondary tumors. Using a preclinical cervical cancer and a melanoma model in mice, we show that single treatment of primary and post-surgery secondary tumors using beDCs resulted in significant tumor growth retardation while multiple inoculations were required to achieve a significant anti-tumor effect when DCs were given in free form. Additionally, we found that, compared to the tumor specific E6/E7 peptide vaccine, total tumor lysate induced higher expression of CD80 and CD40 on DCs that induced increased levels of IFNγ production upon interaction with host lymphocytes. Remarkably, a strong immunocyte infiltration into the host-implanted DC-scaffold was observed. Importantly, the host-implanted beDCs induced the anti-tumor immune responses in the absence of any stromal cell support, and the biomatrix structure was eventually absorbed into the surrounding host tissue. Collectively, these data indicate that the scaffold-based DC delivery may provide an efficient and safe way of delivering cell-based vaccines for treatment of primary and post-surgery secondary tumors. PMID:27223090

Cerebellar transcranial direct current stimulation improves adaptive postural control.

PubMed

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

2018-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2018-02-01

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

Job Stress across Gender: The Importance of Emotional and Intellectual Demands and Social Support in Women

PubMed Central

Rivera-Torres, Pilar; Araque-Padilla, Rafael Angel; Montero-Simó, María José

2013-01-01

This study aims to analyse whether any differences exist between the genders with respect to the effect of perceived Job Demands, Control and Support (JDCS model) on how individuals reach high levels of job stress. To do this, the perceived risk of suffering an illness or having an accident in the workplace is used as an outcome measure. The study is based on the First Survey on Working Conditions in Andalusia, which has a sample of 5,496 men and 2,779 women. We carry out a multi-sample analysis with structural equation models, controlling for age and sector. The results show that the generation of job stress has a different pattern in men and women. In the case of men, the results show that only one dimension of the job demands stressor is significant (quantitative demands), whose effect on job stress is weakened slightly by the direct effects of control and support. With women, in contrast, emotional and intellectual aspects (qualitative demands) are also statistically significant. Moreover, social support has a greater weakening effect on the levels of job stress in women than in men. These results suggest that applying the JDCS model in function of the gender will contribute to a greater understanding of how to reduce the levels of job stress in men and women, helping the design of more effective policies in this area. PMID:23343989

Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization

PubMed Central

Gillick, Bernadette T.; Kirton, Adam; Carmel, Jason B.; Minhas, Preet; Bikson, Marom

2014-01-01

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials. PMID:25285077

Colon Trauma: Evidence-Based Practices.

PubMed

Yamamoto, Ryo; Logue, Alicia J; Muir, Mark T

2018-01-01

Colon injury is not uncommon and occurs in about a half of patients with penetrating hollow viscus injuries. Despite major advances in the operative management of penetrating colon wounds, there remains discussion regarding the appropriate treatment of destructive colon injuries, with a significant amount of scientific evidence supporting segmental resection with primary anastomosis in most patients without comorbidities or large transfusion requirement. Although literature is sparse concerning the management of blunt colon injuries, some studies have shown operative decision based on an algorithm originally defined for penetrating wounds should be considered in blunt colon injuries. The optimal management of colonic injuries in patients requiring damage control surgery (DCS) also remains controversial. Studies have recently reported that there is no increased risk compared with patients treated without DCS if fascial closure is completed on the first reoperation, or that a management algorithm for penetrating colon wounds is probably efficacious for colon injuries in the setting of DCS as well.

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

PubMed

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

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

Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex.

PubMed

Hussey, Erika K; Ward, Nathan; Christianson, Kiel; Kramer, Arthur F

2015-01-01

Recent research demonstrates that performance on executive-control measures can be enhanced through brain stimulation of lateral prefrontal regions. Separate psycholinguistic work emphasizes the importance of left lateral prefrontal cortex executive-control resources during sentence processing, especially when readers must override early, incorrect interpretations when faced with temporary ambiguity. Using transcranial direct current stimulation, we tested whether stimulation of left lateral prefrontal cortex had discriminate effects on language and memory conditions that rely on executive-control (versus cases with minimal executive-control demands, even in the face of task difficulty). Participants were randomly assigned to receive Anodal, Cathodal, or Sham stimulation of left lateral prefrontal cortex while they (1) processed ambiguous and unambiguous sentences in a word-by-word self-paced reading task and (2) performed an n-back memory task that, on some trials, contained interference lure items reputed to require executive-control. Across both tasks, we parametrically manipulated executive-control demands and task difficulty. Our results revealed that the Anodal group outperformed the remaining groups on (1) the sentence processing conditions requiring executive-control, and (2) only the most complex n-back conditions, regardless of executive-control demands. Together, these findings add to the mounting evidence for the selective causal role of left lateral prefrontal cortex for executive-control tasks in the language domain. Moreover, we provide the first evidence suggesting that brain stimulation is a promising method to mitigate processing demands encountered during online sentence processing.

Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex

PubMed Central

Hussey, Erika K.; Ward, Nathan; Christianson, Kiel; Kramer, Arthur F.

2015-01-01

Recent research demonstrates that performance on executive-control measures can be enhanced through brain stimulation of lateral prefrontal regions. Separate psycholinguistic work emphasizes the importance of left lateral prefrontal cortex executive-control resources during sentence processing, especially when readers must override early, incorrect interpretations when faced with temporary ambiguity. Using transcranial direct current stimulation, we tested whether stimulation of left lateral prefrontal cortex had discriminate effects on language and memory conditions that rely on executive-control (versus cases with minimal executive-control demands, even in the face of task difficulty). Participants were randomly assigned to receive Anodal, Cathodal, or Sham stimulation of left lateral prefrontal cortex while they (1) processed ambiguous and unambiguous sentences in a word-by-word self-paced reading task and (2) performed an n-back memory task that, on some trials, contained interference lure items reputed to require executive-control. Across both tasks, we parametrically manipulated executive-control demands and task difficulty. Our results revealed that the Anodal group outperformed the remaining groups on (1) the sentence processing conditions requiring executive-control, and (2) only the most complex n-back conditions, regardless of executive-control demands. Together, these findings add to the mounting evidence for the selective causal role of left lateral prefrontal cortex for executive-control tasks in the language domain. Moreover, we provide the first evidence suggesting that brain stimulation is a promising method to mitigate processing demands encountered during online sentence processing. PMID:26528814

SH2 domain-containing adaptor protein B expressed in dendritic cells is involved in T-cell homeostasis by regulating dendritic cell-mediated Th2 immunity.

PubMed

Ahmed, Md Selim; Kang, Myeong-Ho; Lee, Ezra; Park, Yujin; Jeong, Yideul; Bae, Yong-Soo

2017-01-01

The Src homology 2 domain-containing adaptor protein B (SHB) is widely expressed in immune cells and acts as an important regulator for hematopoietic cell function. SHB silencing induces Th2 immunity in mice. SHB is also involved in T-cell homeostasis in vivo . However, SHB has not yet been studied and addressed in association with dendritic cells (DCs). The effects of SHB expression on the immunogenicity of DCs were assessed by Shb gene silencing in mouse bone marrow-derived DCs (BMDCs). After silencing, surface phenotype, cytokine expression profile, and T-cell stimulation capacity of BMDCs were examined. We investigated the signaling pathways involved in SHB expression during BMDC development. We also examined the immunogenicity of SHB-knockdown (SHB KD ) BMDCs in a mouse atopic dermatitis model. SHB was steadily expressed in mouse splenic DCs and in in vitro -generated BMDCs in both immature and mature stages. SHB expression was contingent on activation of the mitogen- activated protein kinase/Foxa2 signaling pathway during DC development. SHB KD increased the expression of MHC class II and costimulatory molecules without affecting the cytokine expression of BMDCs. When co-cultured with T cells, SHB KD in BMDCs significantly induced CD4 + T-cell proliferation and the expression of Th2 cytokines, while the regulatory T cell (Treg) population was downregulated. In mouse atopic dermatitis model, mice inoculated with SHB KD DCs developed more severe symptoms of atopic dermatitis compared with mice injected with control DCs. SHB expression in DCs plays an important role in T-cell homeostasis in vivo by regulating DC-mediated Th2 polarization.

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

PubMed

Heinitz, Sascha; Reinhardt, Martin; Piaggi, Paolo; Weise, Christopher M; Diaz, Enrique; Stinson, Emma J; Venti, Colleen; Votruba, Susanne B; Wassermann, Eric M; Alonso-Alonso, Miguel; Krakoff, Jonathan; Gluck, Marci E

2017-12-01

Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity. Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake-related appetite ratings in individuals with obesity. Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m 2 ): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables. Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more ( P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals ( P = 0.01), after long-term tDCS. Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. This trial was registered at clinicaltrials.gov as NCT00739362. © 2017 American Society for Nutrition.

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

PubMed Central

de Xivry, Jean-Jacques Orban; Shadmehr, Reza

2014-01-01

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

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

PubMed

Orban de Xivry, Jean-Jacques; Shadmehr, Reza

2014-11-01

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

Leishmania-infected MHC class IIhigh dendritic cells polarize CD4+ T cells toward a nonprotective T-bet+ IFN-γ+ IL-10+ phenotype.

PubMed

Resende, Mariana; Moreira, Diana; Augusto, Jorge; Cunha, Joana; Neves, Bruno; Cruz, Maria Teresa; Estaquier, Jérôme; Cordeiro-da-Silva, Anabela; Silvestre, Ricardo

2013-07-01

A differential behavior among infected and bystander dendritic cells (DCs) has been explored in different infection models. We have analyzed both populations sorted on contact with visceral Leishmania infantum on a susceptible mice model evaluating the subsequent repercussions on adaptive immune response. Our results demonstrate a clear dichotomy between the immunomodulatory abilities of bystander and infected DCs. The bystander population presents increased levels of IL-12p40 and costimulatory molecules being capable to induce CD4(+) T cell activation with immune protective capabilities. In contrast, infected DCs, which express lower costimulatory molecules and higher levels of IL-10, promote the development of Leishmania Ag-specific, nonprotective T-bet(+)IFN-γ(+)IL-10(+) CD4(+) T cells with an effector phenotype. This specific polarization was found to be dependent on IL-12p70. Splenic infected DCs recovered from chronic infected animals are similarly capable to polarize ex vivo syngeneic naive CD4(+) T cells toward a T-bet(+)IFN-γ(+)IL-10(+) phenotype. Further analysis revealed that only MHC class II(high)-infected DCs were responsible for this polarization. The adoptive transfer of such polarized CD4(+) T cells facilitates visceral leishmaniasis in BALB/c mice in a clear contrast with their counterpart generated with bystander DCs that significantly potentiate protection. Further, we demonstrated that CD4(+) T cells primed by infected DCs in an IL-10 free system, thus deprived of T-bet(+)IFN-γ(+)IL-10(+) population, restore the immune response and reduce parasite load, supporting a deleterious role of IFN-γ(+)IL-10(+) T cells in the maintenance of infection. Overall, our results highlight novel subversion mechanisms by which nonprotective T-bet(+)IFN-γ(+)IL-10(+) T cells are associated with chronicity and prolonged parasite persistence.

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

PubMed Central

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

2017-01-01

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

Antifungal Activity of Plasmacytoid Dendritic Cells and the Impact of Chronic HIV Infection.

PubMed

Maldonado, Samuel; Fitzgerald-Bocarsly, Patricia

2017-01-01

Due to the effectiveness of combined antiretroviral therapy, people living with HIV can control viral replication and live longer lifespans than ever. However, HIV-positive individuals still face challenges to their health and well-being, including dysregulation of the immune system resulting from years of chronic immune activation, as well as opportunistic infections from pathogenic fungi. This review focuses on one of the key players in HIV immunology, the plasmacytoid dendritic cell (pDC), which links the innate and adaptive immune response and is notable for being the body's most potent producer of type-I interferons (IFNs). During chronic HIV infection, the pDC compartment is greatly dysregulated, experiencing a substantial depletion in number and compromise in function. This immune dysregulation may leave patients further susceptible to opportunistic infections. This is especially important when considering a new role for pDCs currently emerging in the literature: in addition to their role in antiviral immunity, recent studies suggest that pDCs also play an important role in antifungal immunity. Supporting this new role, pDCs express C-type lectin receptors including dectin-1, dectin-2, dectin-3, and mannose receptor, and toll-like receptors-4 and -9 that are involved in recognition, signaling, and response to a wide variety of fungal pathogens, including Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans , and Pneumocystis jirovecii . Accordingly, pDCs have been demonstrated to recognize and respond to certain pathogenic fungi, measured via activation, cytokine production, and fungistatic activity in vitro , while in vivo mouse models indicated a strikingly vital role for pDCs in survival against pulmonary Aspergillus challenge. Here, we discuss the role of the pDC compartment and the dysregulation it undergoes during chronic HIV infection, as well as what is known so far about the role and mechanisms of pDC antifungal activity.

Prefrontal tDCS Decreases Pain in Patients with Multiple Sclerosis

PubMed Central

Ayache, Samar S.; Palm, Ulrich; Chalah, Moussa A.; Al-Ani, Tarik; Brignol, Arnaud; Abdellaoui, Mohamed; Dimitri, Dalia; Sorel, Marc; Créange, Alain; Lefaucheur, Jean-Pascal

2016-01-01

Background: In the last few years, transcranial direct current stimulation (tDCS) has emerged as an appealing therapeutic option to improve brain functions. Promising data support the role of prefrontal tDCS in augmenting cognitive performance and ameliorating several neuropsychiatric symptoms, namely pain, fatigue, mood disturbances, and attentional impairment. Such symptoms are commonly encountered in patients with multiple sclerosis (MS). Objective: The main objective of the current work was to evaluate the tDCS effects over the left dorsolateral prefrontal cortex (DLPFC) on pain in MS patients.Our secondary outcomes were to study its influence on attention, fatigue, and mood. Materials and Methods: Sixteen MS patients with chronic neuropathic pain were enrolled in a randomized, sham-controlled, and cross-over study.Patients randomly received two anodal tDCS blocks (active or sham), each consisting of three consecutive daily tDCS sessions, and held apart by 3 weeks. Evaluations took place before and after each block. To evaluate pain, we used the Brief Pain Inventory (BPI) and the Visual Analog Scale (VAS). Attention was assessed using neurophysiological parameters and the Attention Network Test (ANT). Changes in mood and fatigue were measured using various scales. Results: Compared to sham, active tDCS yielded significant analgesic effects according to VAS and BPI global scales.There were no effects of any block on mood, fatigue, or attention. Conclusion: Based on our results, anodal tDCS over the left DLPFC appears to act in a selective manner and would ameliorate specific symptoms, particularly neuropathic pain. Analgesia might have occurred through the modulation of the emotional pain network. Attention, mood, and fatigue were not improved in this work. This could be partly attributed to the short protocol duration, the small sample size, and the heterogeneity of our MS cohort. Future large-scale studies can benefit from comparing the tDCS effects over different cortical sites, changing the stimulation montage, prolonging the duration of protocol, and coupling tDCS with neuroimaging techniques for a better understanding of its possible mechanism of action. PMID:27092048

Predictors of new graduate nurses' workplace well-being: testing the job demands-resources model.

PubMed

Spence Laschinger, Heather K; Grau, Ashley L; Finegan, Joan; Wilk, Piotr

2012-01-01

New graduate nurses currently experience a stressful transition into the workforce, resulting in high levels of burnout and job turnover in their first year of practice. This study tested a theoretical model of new graduate nurses' worklife derived from the job demands-resources model to better understand how job demands (workload and bullying), job resources (job control and supportive professional practice environments), and a personal resource (psychological capital) combine to influence new graduate experiences of burnout and work engagement and, ultimately, health and job outcomes. A descriptive correlational design was used to test the hypothesized model in a sample of newly graduated nurses (N = 420) working in acute care hospitals in Ontario, Canada. Data were collected from July to November 2009. Participants were mailed questionnaires to their home address using the Total Design Method to improve response rates. All variables were measured using standardized questionnaires, and structural equation modeling was used to test the model. The final model fit statistics partially supported the original hypothesized model. In the final model, job demands (workload and bullying) predicted burnout and, subsequently, poor mental health. Job resources (supportive practice environment and control) predicted work engagement and, subsequently, lower turnover intentions. Burnout also was a significant predictor of turnover intent (a crossover effect). Furthermore, personal resources (psychological capital) significantly influenced both burnout and work engagement. The model suggests that managerial strategies targeted at specific job demands and resources can create workplace environments that promote work engagement and prevent burnout to support the retention and well-being of the new graduate nurse population.

Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

PubMed

Forbes, Angela S; Regis, David P; Hall, Aaron A; Mahon, Richard T; Cronin, William A

2017-04-01

Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.

PubMed

Thewissen, Kristof; Nuyts, Amber H; Deckx, Nathalie; Van Wijmeersch, Bart; Nagels, Guy; D'hooghe, Marie; Willekens, Barbara; Cras, Patrick; Eijnde, Bert O; Goossens, Herman; Van Tendeloo, Viggo F I; Stinissen, Piet; Berneman, Zwi N; Hellings, Niels; Cools, Nathalie

2014-04-01

The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

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

PubMed

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

2011-03-01

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

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

PubMed

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

2015-10-01

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

New Zealand Diabetes Cohort Study cardiovascular risk score for people with Type 2 diabetes: validation in the PREDICT cohort.

PubMed

Robinson, Tom; Elley, C Raina; Wells, Sue; Robinson, Elizabeth; Kenealy, Tim; Pylypchuk, Romana; Bramley, Dale; Arroll, Bruce; Crengle, Sue; Riddell, Tania; Ameratunga, Shanthi; Metcalf, Patricia; Drury, Paul L

2012-09-01

New Zealand (NZ) guidelines recommend treating people for cardiovascular disease (CVD) risk on the basis of five-year absolute risk using a NZ adaptation of the Framingham risk equation. A diabetes-specific Diabetes Cohort Study (DCS) CVD predictive risk model has been developed and validated using NZ Get Checked data. To revalidate the DCS model with an independent cohort of people routinely assessed using PREDICT, a web-based CVD risk assessment and management programme. People with Type 2 diabetes without pre-existing CVD were identified amongst people who had a PREDICT risk assessment between 2002 and 2005. From this group we identified those with sufficient data to allow estimation of CVD risk with the DCS models. We compared the DCS models with the NZ Framingham risk equation in terms of discrimination, calibration, and reclassification implications. Of 3044 people in our study cohort, 1829 people had complete data and therefore had CVD risks calculated. Of this group, 12.8% (235) had a cardiovascular event during the five-year follow-up. The DCS models had better discrimination than the currently used equation, with C-statistics being 0.68 for the two DCS models and 0.65 for the NZ Framingham model. The DCS models were superior to the NZ Framingham equation at discriminating people with diabetes who will have a cardiovascular event. The adoption of a DCS model would lead to a small increase in the number of people with diabetes who are treated with medication, but potentially more CVD events would be avoided.

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

PubMed

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

2016-01-01

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

Guidewire exchange vs new site placement for temporary dialysis catheter insertion in ICU patients: is there a greater risk of colonization or dysfunction?

PubMed

Coupez, Elisabeth; Timsit, Jean-François; Ruckly, Stéphane; Schwebel, Carole; Gruson, Didier; Canet, Emmanuel; Klouche, Kada; Argaud, Laurent; Bohe, Julien; Garrouste-Orgeas, Maïté; Mariat, Christophe; Vincent, François; Cayot, Sophie; Cointault, Olivier; Lepape, Alain; Darmon, Michael; Boyer, Alexandre; Azoulay, Elie; Bouadma, Lila; Lautrette, Alexandre; Souweine, Bertrand

2016-07-30

Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction. GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction. This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.

PubMed

Kamboj, Sunjeev K; Massey-Chase, Rachel; Rodney, Lydia; Das, Ravi; Almahdi, Basil; Curran, H Valerie; Morgan, Celia J A

2011-09-01

The effects of D-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl D-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect. The objective of this study is to investigate the effect of DCS on exposure/response prevention in heavy drinkers. In a randomised, double-blind, placebo-controlled study, heavy social drinkers recruited from the community received either DCS (125 mg; n = 19) or placebo (n = 17) 1 h prior to each of two sessions of exposure/response prevention. Cue reactivity and attentional bias were assessed during these two sessions and at a third follow-up session. Between-session drinking behaviour was recorded. Robust cue reactivity and attentional bias to alcohol cues was evident, as expected of heavy drinkers. Within- and between-session habituation of cue reactivity, as well as a reduction in attentional bias to alcohol cues over time was found. However, there was no evidence of greater habituation in the DCS group. Subtle stimulant effects (increased subjective contentedness and euphoria) which were unrelated to exposure/response prevention were found following DCS. DCS does not appear to enhance habituation of alcohol cue reactivity in heavy non-dependent drinkers. Its utility in enhancing treatments based on exposure/response prevention in dependent drinkers or drug users remains open.

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

PubMed

Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Perceived information and communication technology (ICT) demands on employee outcomes: the moderating effect of organizational ICT support.

PubMed

Day, Arla; Paquet, Stephanie; Scott, Natasha; Hambley, Laura

2012-10-01

Although many employees are using more information communication technology (ICT) as part of their jobs, few studies have examined the impact of ICT on their well-being, and there is a lack of validated measures designed to assess the ICT factors that may impact employee well-being. Therefore, we developed and validated a measure of ICT demands and supports. Using Exploratory Structural Equation Modeling, we found support for 8 ICT demands (i.e., availability, communication, ICT control, ICT hassles, employee monitoring, learning, response expectations, and workload) and two facets of ICT support (personal assistance and resources/upgrades support). Jointly, the ICT demands were associated with increased strain, stress, and burnout and were still associated with stress and strain after controlling for demographics, job variables, and job demands. The two types of ICT support were associated with lower stress, strain, and burnout. Resources/upgrades support moderated the relationship between learning expectations and most strain outcomes and between ICT hassles and strain. Personal assistance support moderated the relationship between ICT hassles and strain.

Cross-lagged relationships between workplace demands, control, support, and sleep problems.

PubMed

Hanson, Linda L Magnusson; Åkerstedt, Torbjörn; Näswall, Katharina; Leineweber, Constanze; Theorell, Töres; Westerlund, Hugo

2011-10-01

Sleep problems are experienced by a large part of the population. Work characteristics are potential determinants, but limited longitudinal evidence is available to date, and reverse causation is a plausible alternative. This study examines longitudinal, bidirectional relationships between work characteristics and sleep problems. Prospective cohort/two-wave panel. Sweden. 3065 working men and women approximately representative of the Swedish workforce who responded to the 2006 and 2008 waves of the Swedish Longitudinal Occupational Survey of Health (SLOSH). N/A. Bidirectional relationships between, on the one hand, workplace demands, decision authority, and support, and, on the other hand, sleep disturbances (reflecting lack of sleep continuity) and awakening problems (reflecting feelings of being insufficiently restored), were investigated by structural equation modeling. All factors were modeled as latent variables and adjusted for gender, age, marital status, education, alcohol consumption, and job change. Concerning sleep disturbances, the best fitting models were the "forward" causal model for demands and the "reverse" causal model for support. Regarding awakening problems, reciprocal models fitted the data best. Cross-lagged analyses indicates a weak relationship between demands at Time 1 and sleep disturbances at Time 2, a "reverse" relationship from support T1 to sleep disturbances T2, and bidirectional associations between work characteristics and awakening problems. In contrast to an earlier study on demands, control, sleep quality, and fatigue, this study suggests reverse and reciprocal in addition to the commonly hypothesized causal relationships between work characteristics and sleep problems based on a 2-year time lag.

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

PubMed

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

2017-03-01

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

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

PubMed

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.

Towards Data Repository Interoperability: The Data Conservancy Data Packaging Specification

NASA Astrophysics Data System (ADS)

DiLauro, T.; Duerr, R.; Thessen, A. E.; Rippin, M.; Pralle, B.; Choudhury, G. S.

2013-12-01

A modern data archive must support a variety of functions and services for a broad set of stakeholders over a variety of content. Data producers need to deposit this content; data consumers need to find and access it; journal publishers need to link to and from it; funders need to ensure that it is protected and its value enhanced; research institutions need to track it; and the archive itself needs to manage and preserve it. But there is not an optimal information model that supports all of these tasks. The attributes needed to manage format transformations for long-term preservation are different from, for example, those needed to understand provenance relationships among the various entities modeled in the archive. Exposing all possible properties to every function burdens users and makes it difficult to maintain a separation of concerns among the functional components. The Data Conservancy Software (DCS) manages these overlapping information needs by defining strict interfaces between components and providing mappers between the layers of the architecture. Still, work remains to make deposit more intuitive. Currently, depositing content into a DCS instance requires either very simple objects (e.g., one file equals one data item), significant manual effort, or detailed knowledge of DCS-internal data model serializations. And if one were to deposit that content into another type of archive, it would be necessary to repeat this effort. To allow data producers and consumers to interact with data in a more natural manner, the Data Conservancy[1] is developing a packaging approach that eases this burden and allows a semantic overlay atop the directory/folder and file metaphor that is more familiar. The standards-based packaging scheme augments the payload and validation capabilities of Bagit[2] with the relationship and resource description capabilities of the Open Archives Initiative (OAI) Object Reuse and Exchange (ORE)[3] model. In the absence of the ORE resource description, the DCS instance will be able to provide default mappings for the directories and files within the package payload and enable support for deposited content at a lower level of service. Internally, the DCS will map these hybrid package serializations to its own internal business objects and their properties. Thus, this approach is highly extensible, as other packaging formats could be mapped in a similar manner. In addition, this scheme supports establishing the fixity of the payload while still supporting update of the semantic overlay data. This allows a data producer with scarce resources or an archivist who acquires a researcher's data to package the data for deposit with the intention of augmenting the resource description in the future. The Data Conservancy is partnering with the Sustainable Environment Actionable Data[4] project to test the interoperability of this new packaging mechanism. [1] Data Conservancy: http://dataconservancy.org/ [2] BagIt: https://datatracker.ietf.org/doc/draft-kunze-bagit/ [3] OAI-ORE: http://www.openarchives.org/ore/1.0/ [4] SEAD: http://sead-data.net/

Relating Venous Gas Emboli (VGE) Scores to Altitude Decompression Sickness (DCS) Symptoms

NASA Technical Reports Server (NTRS)

Pilmanis, A. A.; Kannan, N.; Krause, K. M.; Webb, J. T.

1999-01-01

Purpose. It is generally accepted that DCS symptoms are caused by gas bubbles in tissues. However, current technology of bubble detection only permits monitoring of circulating bubbles, primarily intracardiac. Since the majority of DCS symptoms appear to be caused by extravascular bubbles, it has been suggested that current bubble detection techniques target bubbles that are of importance in only a minority of DCS cases. The purpose of this study is to determine the relationships between measured VGE and DCS symptoms in human subjects exposed to altitude. Methods. The AFRL DCS Research Database contains records on 2044 subject-exposures to simulated altitudes in a hypobaric chamber. VGE monitoring was accomplished using Doppler/Echo Imaging techniques. The Spencer Scale was used to score the VGE. Reporting of DCS symptoms by the subject was the primary end-point of the exposures. Results: The Mantel- Haenzel test indicated a strong correlation between DCS and bubble grade (p-value =0.001). Conclusions. A positive correlation between increasing VGE scores and DCS symptoms, does not imply causatinn. If all non-zero VGE grades are considered, 45.9% of the cases had VGE, but no DCS symptoms. Conversely, almost 1 in 5 subject-exposures resulted in DCS with NO VGE detected. VGE scores are not . good predictors of altitude DCS symptoms and field use of bubble detection for DCS prevention is not supported by this study.

[Damage control in field surgery].

PubMed

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

2011-09-01

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

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

PubMed Central

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

2015-01-01

IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population. PMID:25658840

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

ERIC Educational Resources Information Center

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

2017-01-01

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

Psychosocial safety climate buffers effects of job demands on depression and positive organizational behaviors.

PubMed

Hall, Garry B; Dollard, Maureen F; Winefield, Anthony H; Dormann, Christian; Bakker, Arnold B

2013-01-01

In a general population sample of 2343 Australian workers from a wide ranging employment demographic, we extended research testing the buffering role of psychosocial safety climate (PSC) as a macro-level resource within the health impairment process of the Job Demands-Resources (JD-R) model. Moderated structural equation modeling was used to test PSC as a moderator between emotional and psychological job demands and worker depression compared with control and social support as alternative moderators. We also tested PSC as a moderator between depression and positive organizational behaviors (POB; engagement and job satisfaction) compared with control and social support as moderators. As expected we found PSC moderated the effects of job demands on depression and further moderated the effects of depression on POB with fit to the data that was as good as control and social support as moderators. This study has shown that PSC is a macro-level resource and safety signal for workers acting to reduce demand-induced depression. We conclude that organizations need to focus on the development of a robust PSC that will operate to buffer the effects of workplace psychosocial hazards and to build environments conducive to worker psychological health and positive organizational behaviors.

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

PubMed

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

2016-05-01

Randomized, controlled pilot trial. The present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tDCS) for pain and patient-controlled analgesia (PCA) opioid usage among patients receiving spine surgery. Lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including tDCS are beginning to demonstrate promise as treatments for a variety of pain conditions. Twenty-seven patients undergoing lumbar spine procedures at Medical University of South Carolina were randomly assigned to receive four 20-minute sessions of real or sham tDCS during their postsurgical hospital stay. Patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. The effect of tDCS on the slope of the cumulative PCA curve was significant (P < 0.001) and tDCS was associated with a 23% reduction in PCA usage. In the real tDCS group a 31% reduction was observed in pain-at-its-least ratings from admission to discharge (P = 0.027), but no other changes in numeric rating scale pain ratings were significant in either group. The present pilot trial is the first study to demonstrate an opioid sparing effect of tDCS after spine surgical procedures. Although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tDCS, suggesting that future work in this area is warranted. 2.

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

PubMed

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

2016-11-01

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

Using bioimpedance spectroscopy parameters as real-time feedback during tDCS.

PubMed

Nejadgholi, Isar; Caytak, Herschel; Bolic, Miodrag

2016-08-01

An exploratory analysis is carried out to investigate the feasibility of using BioImpedance Spectroscopy (BIS) parameters, measured on scalp, as real-time feedback during Transcranial Direct Current Stimulation (tDCS). TDCS is shown to be a potential treatment for neurological disorders. However, this technique is not considered as a reliable clinical treatment, due to the lack of a measurable indicator of treatment efficacy. Although the voltage that is applied on the head is very simple to measure during a tDCS session, changes of voltage are difficult to interpret in terms of variables that affect clinical outcome. BIS parameters are considered as potential feedback parameters, because: 1) they are shown to be associated with the DC voltage applied on the head, 2) they are interpretable in terms of conductive and capacitive properties of head tissues, 3) physical interpretation of BIS measurements makes them prone to be adjusted by clinically controllable variables, 4) BIS parameters are measurable in a cost-effective and safe way and do not interfere with DC stimulation. This research indicates that a quadratic regression model can predict the DC voltage between anode and cathode based on parameters extracted from BIS measurements. These parameters are extracted by fitting the measured BIS spectra to an equivalent electrical circuit model. The effect of clinical tDCS variables on BIS parameters needs to be investigated in future works. This work suggests that BIS is a potential method to be used for monitoring a tDCS session in order to adjust, tailor, or personalize tDCS treatment protocols.

Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.

PubMed

Bravo, Gabriela L; Poje, Albert B; Perissinotti, Iago; Marcondes, Bianca F; Villamar, Mauricio F; Manzardo, Ann M; Luque, Laura; LePage, Jean F; Stafford, Diane; Fregni, Felipe; Butler, Merlin G

2016-03-01

Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P < 0.05, 30 days) and Total Scores (Ƶ = 2.3, P < 0.02, 30 days), and participant ratings of the DHQ Severity (Ƶ = 1.8, P < 0.06, 5 days) and Total Scores (Ƶ = 1.9, P < 0.05, 15 days). These findings support sustained neuromodulatory effects and efficacy of tDCS to reduce food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS. © 2015 Wiley Periodicals, Inc.

CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation1,2

PubMed Central

Thauland, Timothy J.; Koguchi, Yoshinobu; Dustin, Michael L.; Parker, David C.

2014-01-01

Regulatory T cells (Tregs) are essential for tolerance to self and environmental antigens, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naïve CD4 T cell-DC interactions. Here, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down, but maintain a highly polarized and motile phenotype after recognizing antigen in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or ‘kinapse’. However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking antibodies, we show that, while CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of antigen. Together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals. PMID:25355918

Incorporating home demands into models of job strain: findings from the work, family, and health network.

PubMed

Ertel, Karen A; Koenen, Karestan C; Berkman, Lisa F

2008-11-01

The purpose of this article was to integrate home demands with the demand-control-support model to test if home demands interact with job strain to increase depressive symptoms. Data were from 431 employees in four extended care facilities. Presence of a child younger than 18 years in the household signified home demands. The outcome was depressive symptoms based on a shortened version of the Center for Epidemiologic Studies Depression Scale. The association between job strain and depressive symptoms was moderated by social support (SS) and presence of a child in the household (child). There was no association among participants with high SS and no child, but a positive one among participants with low SS and a child. Job strain may be a particularly important determinant of depressive symptoms among employees with family demands. Models of job strain should expand to incorporate family demands.

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

PubMed Central

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

High-Definition Transcranial Direct Current Stimulation Enhances Conditioned Pain Modulation in Healthy Volunteers: A Randomized Trial.

PubMed

Flood, Andrew; Waddington, Gordon; Cathcart, Stuart

2016-05-01

Transcranial direct current stimulation (tDCS) is a form of brain stimulation that allows for the selective increase or decrease in the cortical excitability of a targeted region. When applied over the motor cortex it has been shown to induce changes in cortical and subcortical brain regions involved in descending pain inhibition or conditioned pain modulation (CPM). The aim of the current study was to assess whether activation of pain inhibitory pathways via tDCS of the motor cortex facilitates the CPM response. Elevated CPM after active tDCS of the motor cortex was hypothesized. Thirty healthy male volunteers attended 2 experimental sessions separated by 7 days. Both sessions consisted of CPM assessment after 20 minutes of either active or sham (placebo) tDCS over the motor cortex. CPM capacity was assessed via the pain-inhibits-pain protocol; CPM responses were shown to be elevated after active compared with sham tDCS. This report concludes that tDCS of the motor cortex enhances the CPM response in healthy men. This finding supports the potential utility of tDCS interventions in clinical pain treatment. The use of noninvasive brain stimulation over the motor cortex was shown to enhance the CPM effect. This finding supports the use of tDCS in the treatment of chronic pain, particularly in sufferers exhibiting maladaptive CPM. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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 Index (BI) points; 95% confidence interval (CI) -0.52 to 11.14; inverse variance method with random-effects model), whereas at follow-up (MD 11.13 BI points; 95% CI 2.89 to 19.37; inverse variance method with random-effects model), we found evidence of an effect. However, the confidence intervals were wide and the effect was not sustained when only studies with low risk of bias were included. For our secondary outcome, upper limb function, we analysed eight trials with 358 participants, which showed evidence of an effect in favour of tDCS at the end of the intervention phase (MD 3.45 Upper Extremity Fugl-Meyer Score points (UE-FM points); 95% CI 1.24 to 5.67; inverse variance method with random-effects model) but not at the end of follow-up three months after the intervention (MD 9.23 UE-FM points; 95% CI -13.47 to 31.94; inverse variance method with random-effects model). These results were sensitive to inclusion of studies at high risk of bias. Adverse events were reported and the proportions of dropouts and adverse events were comparable between groups (risk difference (RD) 0.00; 95% CI -0.02 to 0.03; Mantel-Haenszel method with random-effects model). At the moment, evidence of very low to low quality is available on the effectiveness of tDCS (anodal/cathodal/dual) versus control (sham/any other intervention) for improving ADL performance and function after stroke. Future research should investigate the effects of tDCS on lower limb function and should address methodological issues by routinely reporting data on adverse events and dropouts and allocation concealment, and by performing intention-to-treat analyses.

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

PubMed Central

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

2017-01-01

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

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

PubMed Central

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

2016-01-01

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

BDNF Val66Met but not transcranial direct current stimulation affects motor learning after stroke.

PubMed

van der Vliet, Rick; Ribbers, Gerard M; Vandermeeren, Yves; Frens, Maarten A; Selles, Ruud W

tDCS is a non-invasive neuromodulation technique that has been reported to improve motor skill learning after stroke. However, the contribution of tDCS to motor skill learning has only been investigated in a small number of studies. In addition, it is unclear if tDCS effects are mediated by activity-dependent BDNF release and dependent on timing of tDCS relative to training. Investigate the role of activity-dependent BDNF release and timing of tDCS relative to training in motor skill learning. Double-blind, between-subjects randomized controlled trial of circuit tracing task improvement (ΔMotor skill) in 80 chronic stroke patients who underwent tDCS and were genotyped for BDNF Val66Met. Patients received either short-lasting tDCS (20 min) during training (short-lasting online group), long-lasting tDCS (10 min-25 min break - 10 min) one day before training (long-lasting offline group), short-lasting tDCS one day before training (short-lasting offline group), or sham tDCS. ΔMotor skill was defined as the skill difference on the circuit tracing task between day one and day nine of the study. Having at least one BDNF Met allele was found to diminish ΔMotor skill (β BDNF,Met  = -0.217 95%HDI = [-0.431 -0.0116]), indicating activity-dependent BDNF release is important for motor skill learning after stroke. However, none of the tDCS protocols affected ΔMotor skill (β Short-lasting,online  = 0.0908 95%HDI = [-0.227 0.403]; β Long-lasting,offline  = 0.0242 95%HDI = [-0.292 0.349]; β Short-lasting,offline  = -0.108 95%HDI = [-0.433 0.210]). BDNF Val66Met is a determinant of motor skill learning after stroke and could be important for prognostic models. tDCS does not modulate motor skill learning in our study and might be less effective than previously assumed. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-12-01

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

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

PubMed

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

2011-06-01

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

The role of early stages of cortical visual processing in size and distance judgment: a transcranial direct current stimulation study.

PubMed

Costa, Thiago L; Costa, Marcelo F; Magalhães, Adsson; Rêgo, Gabriel G; Nagy, Balázs V; Boggio, Paulo S; Ventura, Dora F

2015-02-19

Recent research suggests that V1 plays an active role in the judgment of size and distance. Nevertheless, no research has been performed using direct brain stimulation to address this issue. We used transcranial direct-current stimulation (tDCS) to directly modulate the early stages of cortical visual processing while measuring size and distance perception with a psychophysical scaling method of magnitude estimation in a repeated-measures design. The subjects randomly received anodal, cathodal, and sham tDCS in separate sessions starting with size or distance judgment tasks. Power functions were fit to the size judgment data, whereas logarithmic functions were fit to distance judgment data. Slopes and R(2) were compared with separate repeated-measures analyses of variance with two factors: task (size vs. distance) and tDCS (anodal vs. cathodal vs. sham). Anodal tDCS significantly decreased slopes, apparently interfering with size perception. No effects were found for distance perception. Consistent with previous studies, the results of the size task appeared to reflect a prothetic continuum, whereas the results of the distance task seemed to reflect a metathetic continuum. The differential effects of tDCS on these tasks may support the hypothesis that different physiological mechanisms underlie judgments on these two continua. The results further suggest the complex involvement of the early visual cortex in size judgment tasks that go beyond the simple representation of low-level stimulus properties. This supports predictive coding models and experimental findings that suggest that higher-order visual areas may inhibit incoming information from the early visual cortex through feedback connections when complex tasks are performed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

A Log Logistic Survival Model Applied to Hypobaric Decompression Sickness

NASA Technical Reports Server (NTRS)

Conkin, Johnny

2001-01-01

Decompression sickness (DCS) is a complex, multivariable problem. A mathematical description or model of the likelihood of DCS requires a large amount of quality research data, ideas on how to define a decompression dose using physical and physiological variables, and an appropriate analytical approach. It also requires a high-performance computer with specialized software. I have used published DCS data to develop my decompression doses, which are variants of equilibrium expressions for evolved gas plus other explanatory variables. My analytical approach is survival analysis, where the time of DCS occurrence is modeled. My conclusions can be applied to simple hypobaric decompressions - ascents lasting from 5 to 30 minutes - and, after minutes to hours, to denitrogenation (prebreathing). They are also applicable to long or short exposures, and can be used whether the sufferer of DCS is at rest or exercising at altitude. Ultimately I would like my models to be applied to astronauts to reduce the risk of DCS during spacewalks, as well as to future spaceflight crews on the Moon and Mars.

Potential Fifty Percent Reduction in Saturation Diving Decompression Time Using a Combination of Intermittent Recompression and Exercise

NASA Technical Reports Server (NTRS)

Gernhardt, Michael I.; Abercromby, Andrew; Conklin, Johnny

2007-01-01

Conventional saturation decompression protocols use linear decompression rates that become progressively slower at shallower depths, consistent with free gas phase control vs. dissolved gas elimination kinetics. If decompression is limited by control of free gas phase, linear decompression is an inefficient strategy. The NASA prebreathe reduction program demonstrated that exercise during O2 prebreathe resulted in a 50% reduction (2 h vs. 4 h) in the saturation decompression time from 14.7 to 4.3 psi and a significant reduction in decompression sickness (DCS: 0 vs. 23.7%). Combining exercise with intermittent recompression, which controls gas phase growth and eliminates supersaturation before exercising, may enable more efficient saturation decompression schedules. A tissue bubble dynamics model (TBDM) was used in conjunction with a NASA exercise prebreathe model (NEPM) that relates tissue inert gas exchange rate constants to exercise (ml O2/kg-min), to develop a schedule for decompression from helium saturation at 400 fsw. The models provide significant prediction (p < 0.001) and goodness of fit with 430 cases of DCS in 6437 laboratory dives for TBDM (p = 0.77) and with 22 cases of DCS in 159 altitude exposures for NEPM (p = 0.70). The models have also been used operationally in over 25,000 dives (TBDM) and 40 spacewalks (NEPM). The standard U.S. Navy (USN) linear saturation decompression schedule from saturation at 400 fsw required 114.5 h with a maximum Bubble Growth Index (BGI(sub max)) of 17.5. Decompression using intermittent recompression combined with two 10 min exercise periods (75% VO2 (sub peak)) per day required 54.25 h (BGI(sub max): 14.7). Combined intermittent recompression and exercise resulted in a theoretical 53% (2.5 day) reduction in decompression time and theoretically lower DCS risk compared to the standard USN decompression schedule. These results warrant future decompression trials to evaluate the efficacy of this approach.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2015-04-01

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

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

PubMed

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

2013-11-01

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

Effect of pore size of three-dimensionally ordered macroporous chitosan-silica matrix on solubility, drug release, and oral bioavailability of loaded-nimodipine.

PubMed

Gao, Yikun; Xie, Yuling; Sun, Hongrui; Zhao, Qinfu; Zheng, Xin; Wang, Siling; Jiang, Tongying

2016-01-01

To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan-silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug. 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated. With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively. Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.

Effects of transcranial direct current stimulation of primary somatosensory cortex on vibrotactile detection and discrimination

PubMed Central

Labbé, Sara; Meftah, El-Mehdi

2016-01-01

Anodal transcranial direct current stimulation (a-tDCS) of primary somatosensory cortex (S1) has been shown to enhance tactile spatial acuity, but there is little information as to the underlying neuronal mechanisms. We examined vibrotactile perception on the distal phalanx of the middle finger before, during, and after contralateral S1 tDCS [a-, cathodal (c)-, and sham (s)-tDCS]. The experiments tested our shift-gain hypothesis, which predicted that a-tDCS would decrease vibrotactile detection and discrimination thresholds (leftward shift of the stimulus-response function with increased gain/slope) relative to s-tDCS, whereas c-tDCS would have the opposite effects (relative to s-tDCS). The results showed that weak a-tDCS (1 mA, 20 min) led to a reduction in both vibrotactile detection and discrimination thresholds to 73–76% of baseline during the application of the stimulation in subjects categorized as responders. These effects persisted after the end of a-tDCS but were absent 30 min later. Most, but not all, subjects showed a decrease in threshold (8/12 for detection; 9/12 for discrimination). Intersubject variability was explained by a ceiling effect in the discrimination task. c-tDCS had no significant effect on either detection or discrimination threshold. Taken together, our results supported our shift-gain hypothesis for a-tDCS but not c-tDCS. PMID:26864757

Thoracic Inlet Parameters for Degenerative Cervical Spondylolisthesis Imaging Measurement.

PubMed

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

2018-04-05

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

The effect of simulated weightlessness on hypobaric decompression sickness

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Association of work-related stress with mental health problems in a special police force unit.

PubMed

Garbarino, Sergio; Cuomo, Giovanni; Chiorri, Carlo; Magnavita, Nicola

2013-01-01

Law and order enforcement tasks may expose special force police officers to significant psychosocial risk factors. The aim of this work is to investigate the relationship between job stress and the presence of mental health symptoms while controlling sociodemographical, occupational and personality variables in special force police officers. At different time points, 292 of 294 members of the 'VI Reparto Mobile', a special police force engaged exclusively in the enforcement of law and order, responded to our invitation to complete questionnaires for the assessment of personality traits, work-related stress (using the Demand-Control-Support (DCS) and the Effort-Reward-Imbalance (ERI) models) and mental health problems such as depression, anxiety and burnout. Regression analyses showed that lower levels of support and reward and higher levels of effort and overcommitment were associated with higher levels of mental health symptoms. Psychological screening revealed 21 (7.3%) likely cases of mild depression (Beck Depression Inventory, BDI≥10). Officers who had experienced a discrepancy between work effort and rewards showed a marked increase in the risk of depression (OR 7.89, 95% CI 2.32 to 26.82) when compared with their counterparts who did not perceive themselves to be in a condition of distress. The findings of this study suggest that work-related stress may play a role in the development of mental health problems in police officers. The prevalence of mental health symptoms in the cohort investigated here was low, but not negligible in the case of depression. Since special forces police officers have to perform sensitive tasks for which a healthy psychological functioning is needed, the results of this study suggest that steps should be taken to prevent distress and improve the mental well-being of these workers.

Validation of a Measure of Non-Commissioned Officer Leadership

DTIC Science & Technology

2006-01-20

trauma, aside from injury, include cardiovascular distress and somatic complaints (Belkic, Emdad, & Theorell , 1998; Zatzick, Russo, & Katon, 2003...hypothesis emerged from the DC model, and posits that high strain jobs are characterized as high in demands and low in control ( Karasek , 1979). NCO...leadership three months following a combat deployment, in the context of Leader-Member Exchange theory (Graen, 1976), Demand-Control-Support model ( Karasek

Occupational coping self-efficacy explains distress and well-being in nurses beyond psychosocial job characteristics

PubMed Central

Pisanti, Renato; van der Doef, Margot; Maes, Stan; Lombardo, Caterina; Lazzari, David; Violani, Cristiano

2015-01-01

Aim: The main purpose of the present study was to extend the Job Demand Control Support (JDCS) model analyzing the direct and interactive role of occupational coping self-efficacy (OCSE) beliefs. Background: OCSE refers to an individual’s beliefs about their ability to cope with occupational stressors. The interplay between occupational stressors, job resources, and self-efficacy beliefs is poorly investigated. The present research attempts to address this gap. Design: Cross-sectional survey. Method: Questionnaire data from 1479 nurses (65% response) were analyzed. Hierarchical regression analyses were used to test the direct and moderating role of OCSE in conjunction with job demands (i.e., time pressure), and two job resources: job control (i.e., decision latitude and skill discretion) and social support (i.e., supervisor support and coworker support) in predicting psychological distress and well-being. Results: Our findings indicated that high demands, low job control, and low social support additively predicted the distress/well-being outcomes (job satisfaction, emotional exhaustion, depersonalization, psychological distress, and somatic complaints). Beyond the main effects, no significant interactive effects of demands, control, and support were found. OCSE accounted for an additional 1–4% of the variance in the outcomes, after controlling for the JDCS variables. In addition, the results indicate that OCSE buffers the association between low job control and the distress dimensions emotional exhaustion, depersonalization, and psychological distress. Low control was detrimental only for nurses with low OCSE. Conclusion: Our results suggest expanding the JDCS model incorporating individual characteristics such as OCSE beliefs, for predicting psychological distress and well-being. Limitations of the study and practical implications are discussed. PMID:26300827

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

PubMed

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

2012-09-01

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

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

PubMed

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

2017-05-01

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

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

PubMed

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

2017-10-01

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

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

NASA Astrophysics Data System (ADS)

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 (\

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

PubMed Central

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

2009-01-01

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

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

PubMed Central

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:28659772

Job demands-control-social support model and coping strategies: predicting burnout and wellbeing in a group of Italian nurses.

PubMed

Pisanti, R

2012-01-01

Nursing is generally considered to be a stressful profession. The purpose of the present study was to test the core hypotheses of the job demands-control-social support model (JDCS) of Karasek & Theorell (1990). In order to refine and extend the JDCS model, we also analyzed the direct and interactive role of three coping strategies: task- oriented, emotion-oriented, and avoidance-oriented coping. Questionnaire data from 1383 nurses (77%female) were collected. Controlling for demographic variables and non-linearity of the associations between job characteristics and outcomes (job satisfaction; burnout dimensions, psychological distress, and somatic complaints), hierarchical regression analyses indicated that job control and social support combined additively (p < 0.001) with job demands to explain the wellbeing outcomes (explained variance between 6% and 28%). Coping strategies accounted for additional variance (p < 0.001; explained variance between 4% and 15%) in all outcomes except in job satisfaction. Support was found for main effects of coping. Coping strategies did not moderate the impact of job characteristics on burnout and wellbeing. Emotion-oriented coping emerged as the most important predictor and was consistently associated with higher burnout levels and lower wellbeing levels. The results demonstrated the need to include the role of individual variables in the JDCS model. The limitations of the study, and theoretical and practical implications are discussed.

Trichinella spiralis Excretory–Secretory Products Induce Tolerogenic Properties in Human Dendritic Cells via Toll-Like Receptors 2 and 4

PubMed Central

Ilic, Nataša; Gruden-Movsesijan, Alisa; Cvetkovic, Jelena; Tomic, Sergej; Vucevic, Dragana Bozidar; Aranzamendi, Carmen; Colic, Miodrag; Pinelli, Elena; Sofronic-Milosavljevic, Ljiljana

2018-01-01

Trichinella spiralis, as well as its muscle larvae excretory–secretory products (ES L1), given either alone or via dendritic cells (DCs), induce a tolerogenic immune microenvironment in inbred rodents and successfully ameliorate experimental autoimmune encephalomyelitis. ES L1 directs the immunological balance away from T helper (Th)1, toward Th2 and regulatory responses by modulating DCs phenotype. The ultimate goal of our work is to find out if it is possible to translate knowledge obtained in animal model to humans and to generate human tolerogenic DCs suitable for therapy of autoimmune diseases through stimulation with ES L1. Here, the impact of ES L1 on the activation of human monocyte-derived DCs is explored for the first time. Under the influence of ES L1, DCs acquired tolerogenic (semi-matured) phenotype, characterized by low expression of HLA-DR, CD83, and CD86 as well as moderate expression of CD40, along with the unchanged production of interleukin (IL)-12 and elevated production of IL-10 and transforming growth factor (TGF)-β, compared to controls. The interaction with DCs involved toll-like receptors (TLR) 2 and 4, and this interaction was mainly responsible for the phenotypic and functional properties of ES L1-treated DCs. Importantly, ES L1 potentiated Th2 polarizing capacity of DCs, and impaired their allo-stimulatory and Th1/Th17 polarizing properties. Moreover, ES L1-treated DCs promoted the expansion of IL-10- and TGF-β- producing CD4+CD25hiFoxp3hi T cells in indolamine 2, 3 dioxygenase (IDO)-1-dependent manner and increased the suppressive potential of the primed T cell population. ES L1-treated DCs retained the tolerogenic properties, even after the challenge with different pro-inflammatory stimuli, including those acting via TLR3 and, especially TLR4. These results suggest that the induction of tolerogenic properties of DCs through stimulation with ES L1 could represent an innovative approach for the preparation of tolerogenic DC for treatment of inflammatory and autoimmune disorders. PMID:29416536

Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.

PubMed

Zhang, Bin; Liu, Rui; Shi, Dan; Liu, Xingxia; Chen, Yuan; Dou, Xiaowei; Zhu, Xishan; Lu, Chunhua; Liang, Wei; Liao, Lianming; Zenke, Martin; Zhao, Robert C H

2009-01-01

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

Animal models of transcranial direct current stimulation: Methods and mechanisms.

PubMed

Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom

2016-11-01

The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the complexity of normal and pathological brain function, and how recent studies have already indicated more sophisticated approaches are necessary. One tDCS theory regarding "functional targeting" suggests the specificity of tDCS effects are possible by modulating ongoing function (plasticity). Use of animal models of disease are summarized including pain, movement disorders, stroke, and epilepsy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Animal Models of transcranial Direct Current Stimulation: Methods and Mechanisms

PubMed Central

Jackson, Mark P.; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C.; Bikson, Marom

2016-01-01

The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: 1) transcranial stimulation; 2) direct cortical stimulation in vivo and 3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching “quasi-uniform” assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the complexity of normal and pathological brain function, and how recent studies have already indicated more sophisticated approaches are necessary. One tDCS theory regarding “functional targeting” suggests the specificity of tDCS effects are possible by modulating ongoing function (plasticity). Use of animal models of disease are summarized including pain, movement disorders, stroke, and epilepsy. PMID:27693941

Effects of Individual Differences and Job Characteristics on the Psychological Health of Italian Nurses

PubMed Central

Zurlo, Maria Clelia; Vallone, Federica; Smith, Andrew P.

2018-01-01

The Demand Resources and Individual Effects Model (DRIVE Model) is a transactional model that integrates Demands- Control-Support and Effort-Reward Imbalance models emphasising the role of individual (Coping Strategies; Overcommitment) and job characteristics (Job Demands, Social Support, Decision Latitude, Skill Discretion, Effort, Rewards) in the work-related stress process. The present study aimed to test the DRIVE Model in a sample of 450 Italian nurses and to compare findings with those of a study conducted in a sample of UK nurses. A questionnaire composed of Ways of Coping Checklist-Revised (WCCL-R); Job Content Questionnaire (JCQ); ERI Test; Hospital Anxiety and Depression Scale (HADS) was used. Data supported the application of the DRIVE Model to the Italian context, showing significant associations of the individual characteristics of Problem-focused, Seek Advice and Wishful Thinking coping strategies and the job characteristics of Job Demands, Skill Discretion, Decision Latitude, and Effort with perceived levels of Anxiety and Depression. Effort represented the best predictor for psychological health conditions among Italian nurses, and Social Support significantly moderated the effects of Job Demands on perceived levels of Anxiety. The comparison study showed significant differences in the risk profiles of Italian and UK nurses. Findings were discussed in order to define focused interventions to promote nurses’ wellbeing.

The Integration of DCS I/O to an Existing PLC

NASA Technical Reports Server (NTRS)

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.

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

PubMed

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

2014-01-01

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

Presenting risk information to people with diabetes: evaluating effects and preferences for different formats by a web-based randomised controlled trial.

PubMed

Edwards, Adrian; Thomas, Richard; Williams, Rhys; Ellner, Andrew L; Brown, Polly; Elwyn, Glyn

2006-11-01

Web-based patient information is widespread and information on the benefits and risks of treatments is often difficult to understand. We therefore evaluated different risk presentation formats - numerical, graphical and others - addressing the pros and cons of tight control versus usual treatment approaches for diabetes. Randomised controlled trial. Online. Publicity disseminated via Diabetes UK. People with diabetes or their carers. Control group information based on British Medical Journal 'Best Treatments'. Four intervention groups received enhanced information resources: (1) detailed numerical information (absolute/relative risk, numbers-needed-to-treat); (2) 'anchoring' to familiar risks or descriptions; (3) graphical (bar charts, thermometer scales, crowd figure formats); (4) combination of 1-3. Decision conflict scale (DCS, a measure of uncertainty); satisfaction with information; further free text responses for qualitative content analysis. Seven hundred and ten people visited the website and were randomised. Five hundred and eight completed the questionnaire for quantitative data. Mean DCS scores ranged from 2.12 to 2.24 for the five randomisation groups, indicating neither clear delay or vacillation about decisions (usually DCS>2.5) nor tending to make decisions (usually DCS<2.0). There were no statistically significant effects of the interventions on DCS, or satisfaction with information. Two hundred and fifty-six participants provided responses for qualitative analysis: most found graphical representations helpful, specifically bar chart formats; many found other graphic formats (thermometer style, crowd figures/smiley faces) and 'anchoring' information unhelpful, and indicated information overload. Many negative experiences with healthcare indicate a challenging context for effective information provision and decision support. Online evaluation of different risk representation formats was feasible. There was a lack of intervention effects on quantitative outcomes, perhaps reflecting already well-informed participants from the Diabetes UK patient organisation. The large qualitative dataset included many comments about what participants found helpful as formats for communicating risk information. These findings assist the design of online decision aids and the representation of risk information. The challenge is to provide more information, in appropriate and clear formats, but without risking information overload. Interactive web designs hold much promise to achieve this.

Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice.

PubMed

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.

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

PubMed

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

2015-06-15

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

Strategies and Pitfalls of Motor-Evoked Potential Monitoring during Supratentorial Aneurysm Surgery.

PubMed

Maruta, Yuichi; Fujii, Masami; Imoto, Hirochika; Nomura, Sadahiro; Tanaka, Nobuhiro; Inamura, Akinori; Sadahiro, Hirokazu; Oka, Fumiaki; Goto, Hisaharu; Shirao, Satoshi; Ideguchi, Makoto; Yoneda, Hiroshi; Suehiro, Eiichi; Koizumi, Hiroyasu; Ishihara, Hideyuki; Suzuki, Michiyasu

2016-02-01

The aims of this study were to reveal the strategies and pitfalls of motor-evoked potential (MEP) monitoring methods during supratentorial aneurysm surgery, and to discuss the drawbacks and advantages of each method by reviewing our experiences. Intraoperative MEP monitoring was performed in 250 patients. Results from 4 monitoring techniques using combinations of 2 stimulation sites and 2 recording sites were analyzed retrospectively. MEP was recorded successfully in 243 patients (97.2%). Direct cortical stimulation (DCS)-spinal recorded MEP (sMEP) was used in 134 patients, DCS-muscle recorded MEP (mMEP) in 97, transcranial electrical stimulation (TES)-mMEP in 11 and TES-sMEP in 1. TES-mMEP during closure of the skull was used in 21 patients. DCS-mMEP was able to detect waveforms from upper and/or lower limb muscles. Alternatively, DCS-sMEP (direct [D]-wave) could accurately estimate amplitude changes. A novel "early warning sign" indicating ischemia was found in 21 patients, which started with a transiently increased amplitude of D-wave and then decreased after proximal interruption of major arteries. False-negative findings in MEP monitoring in 2 patients were caused by a blood insufficiency in the lenticulostriate artery and by a TES-sMEP recording, respectively. The results of this study suggest that to perform accurate MEP monitoring, DCS-mMEP or DCS-sMEP recording should be used as the situation demands, with combined use of TES-mMEP recording during closure of the skull. DCS-sMEP is recommended for accurate analysis of waveforms. We also propose a novel "early warning sign" of blood insufficiency in the D-wave. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Neurocognitive mechanisms behind emotional attention: Inverse effects of anodal tDCS over the left and right DLPFC on gaze disengagement from emotional faces.

PubMed

Sanchez-Lopez, Alvaro; Vanderhasselt, Marie-Anne; Allaert, Jens; Baeken, Chris; De Raedt, Rudi

2018-06-01

Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted. A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions). Compared to sham, active tDCS over the left DLPFC led to faster gaze disengagement, whereas active tDCS over the right DLPFC led to slower gaze disengagement from emotional faces. Between-group comparisons showed that such inverse change patterns were significantly different and generalized for all types of emotion. Our findings support a lateralized role of left and right DLPFC activity in enhancing/worsening the top-down regulation of emotional attention processing. These results support the rationale of new therapies for affective disorders aimed to increase the activation of the left over the right DLPFC in combination with attentional control training, and identify specific target attention mechanisms to be trained.

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

PubMed Central

Jacoby, Noa; Lavidor, Michal

2018-01-01

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

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

PubMed

Jacoby, Noa; Lavidor, Michal

2018-01-01

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

A new method for assessment of the sludge disintegration degree with the use of differential centrifugal sedimentation.

PubMed

Silvestri, Daniele; Wacławek, Stanisław; Gončuková, Zuzanna; Padil, Vinod V T; Grübel, Klaudiusz; Černík, Miroslav

2018-05-24

A novel method for assessing the disintegration degree (DD) of waste activated sludge (WAS) with the use of differential centrifugal sedimentation method (DCS) was shown herein. The method was validated for a WAS sample at four levels of disintegration in the range of 14.4-82.6% corresponding to the median particle size range of 8.5-1.6 µm. From the several sludge disintegration methods used (i.e. microwave, alkalization, ultrasounds and peroxydisulfate activated by ultrasounds), the activated peroxydisulfate disintegration resulted in the greatest DD 83% and the smallest median particle size of WAS. Particle size distribution of pretreated sludge, measured by DCS, was in a negative correlation with the DD, determined from soluble chemical oxygen demand (SCOD; determination coefficient of 0.995). Based on the obtained results, it may be concluded that the DCS analysis can approximate the WAS disintegration degree.

Transcranial Direct Current Stimulation to Enhance Dual-Task Gait Training in Parkinson's Disease: A Pilot RCT.

PubMed

Schabrun, Siobhan M; Lamont, Robyn M; Brauer, Sandra G

2016-01-01

To investigate the feasibility and safety of a combined anodal transcranial direct current stimulation (tDCS) and dual task gait training intervention in people with Parkinson's Disease (PD) and to provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. A pilot, randomized, double-blind, sham-controlled parallel group trial with 12 week follow-up. A university physiotherapy department. Sixteen participants diagnosed with PD received nine dual task gait training sessions over 3 weeks. Participants were randomized to receive either active or sham tDCS applied for the first 20 minutes of each session. The primary outcome was gait speed while undertaking concurrent cognitive tasks (word lists, counting, conversation). Secondary measures included step length, cadence, Timed Up and Go, bradykinesia and motor speed. Gait speed, step length and cadence improved in both groups, under all dual task conditions. This effect was maintained at follow-up. There was no difference between the active and sham tDCS groups. Time taken to perform the TUGwords also improved, with no difference between groups. The active tDCS group did however increase their correct cognitive response rate during the TUGwords and TUGcount. Bradykinesia improved after training in both groups. Three weeks of dual task gait training resulted in improved gait under dual task conditions, and bradykinesia, immediately following training and at 12 weeks follow-up. The only parameter enhanced by tDCS was the number of correct responses while performing the dual task TUG. tDCS applied to M1 may not be an effective adjunct to dual task gait training in PD. Australia-New Zealand Clinical Trials Registry ACTRN12613001093774.

Effector and regulatory dendritic cells display distinct patterns of miRNA expression.

PubMed

Lombardi, Vincent; Luce, Sonia; Moussu, Hélène; Morizur, Lise; Gueguen, Claire; Neukirch, Catherine; Chollet-Martin, Sylvie; Mascarell, Laurent; Aubier, Michel; Baron-Bodo, Véronique; Moingeon, Philippe

2017-09-01

MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome. Using specific culture conditions, we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of T H 1, T H 2 or regulatory T cells, respectively). Profiling of miRNA expression was performed in these DC subpopulations using microarrays. Levels of miRNAs specific for polarized DCs were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non-allergic controls, as well as in samples from 30 subjects treated with sublingual grass pollen tablets or placebo for four months. We successfully identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of those miRNAs (miR-132 and miR-155), was down-regulated compared to non-allergic individuals. However, the levels of these miRNAs were not significantly modified following four months of grass pollen immunotherapy. Studying polarized DCs and clinical samples from subjects with or without allergic rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent relevant biomarkers to predict or follow-up AIT efficacy. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Effector and regulatory dendritic cells display distinct patterns of miRNA expression

PubMed Central

Luce, Sonia; Moussu, Hélène; Morizur, Lise; Gueguen, Claire; Neukirch, Catherine; Chollet‐Martin, Sylvie; Mascarell, Laurent; Aubier, Michel; Baron‐Bodo, Véronique; Moingeon, Philippe

2017-01-01

Abstract Introduction MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome. Method Using specific culture conditions, we differentiated immature human monocyte‐derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of TH1, TH2 or regulatory T cells, respectively). Profiling of miRNA expression was performed in these DC subpopulations using microarrays. Levels of miRNAs specific for polarized DCs were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non‐allergic controls, as well as in samples from 30 subjects treated with sublingual grass pollen tablets or placebo for four months. Results We successfully identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of those miRNAs (miR‐132 and miR‐155), was down‐regulated compared to non‐allergic individuals. However, the levels of these miRNAs were not significantly modified following four months of grass pollen immunotherapy. Conclusions Studying polarized DCs and clinical samples from subjects with or without allergic rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent relevant biomarkers to predict or follow‐up AIT efficacy. PMID:28497578

[Noninvasive cerebral stimulation for treatment of ADHD: A review of the literature].

PubMed

Brandejsky, L; Micoulaud Franchi, J-A; Lopez, R; Bioulac, S; Da Fonseca, D; Daudet, C; Boyer, L; Richieri, R; Lançon, C

2017-10-01

The aim of this review is to summarize the available data in the literature about the therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in attention-deficit hyperactivity disorder (ADHD). The scientific literature search of international articles was performed in February 2016 using the PubMed electronic database. The following MeSH terms were employed: "attention-deficit disorder with hyperactivity" AND "transcranial magnetic stimulation", "attention-deficit disorder with hyperactivity" AND "transcranial direct current stimulation". Five studies were retained by the literature search and were included in the review about rTMS and ADHD. Except for one study, they all showed significant positive effects of rTMS on ADHD. Four studies were retained by the literature search and were included in the review about tDCS and ADHD. Three of them showed significant positive effects of tDCS on ADHD. Two of them used tDCS during sleep at a frequency<1Hz. Only low-level evidences are available to support treatment with rTMS or tDCS in patients with ADHD. Indeed, randomized controlled trials are rare in this field of research. Additional studies are needed to confirm the efficacy of rTMS and tDCS in ADHD. rTMS could be used as an alternative therapy when methylphenidate is not well tolerated or shows an insufficient efficacy. Nevertheless, the optimal target, frequency and duration remain to be determined. tDCS can modulate attention in healthy subjects but data are insufficient in ADHD to conclude. It could be interesting to study its use in association with cognitive remediation to enhance its cognitive efficacy. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

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

PubMed

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.

USDI DCS technical support: Mississippi Test Facility

NASA Technical Reports Server (NTRS)

Preble, D. M.

1975-01-01

The objective of the technical support effort is to provide hardware and data processing support to DCS users so that application of the system may be simply and effectively implemented. Technical support at Mississippi Test Facility (MTF) is concerned primarily with on-site hardware. The first objective of the DCP hardware support was to assure that standard measuring apparatus and techniques used by the USGS could be adapted to the DCS. The second objective was to try to standardize the miscellaneous variety of parameters into a standard instrument set. The third objective was to provide the necessary accessories to simplify the use and complement the capabilities of the DCP. The standard USGS sites have been interfaced and are presently operating. These sites are stream gauge, ground water level and line operated quality of water. Evapotranspiration, meteorological and battery operated quality of water sites are planned for near future DCP operation. Three accessories which are under test or development are the Chu antenna, solar power supply and add-on memory. The DCP has proven to be relatively easy to interface with many monitors. The large antenna is awkward to install and transport. The DCS has met the original requirements well; it has and is proving that an operation, satellite-based data collection system is feasible.

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

PubMed

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

2011-03-01

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

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

PubMed Central

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

2015-01-01

Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. PMID:25934490

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

PubMed

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

2017-12-01

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

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

PubMed

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

2016-07-19

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

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

PubMed Central

Veinotte, Linnea; Gebremeskel, Simon; Johnston, Brent

2016-01-01

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

Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption.

PubMed

Pedron, Solène; Monnin, Julie; Haffen, Emmanuel; Sechter, Daniel; Van Waes, Vincent

2014-03-01

Successful available treatments to quit smoking remain scarce. Recently, the potential of transcranial direct current stimulation (tDCS) as a tool to reduce craving for nicotine has gained interest. However, there is no documented animal model to assess the neurobiological mechanisms of tDCS on addiction-related behaviors. To address this topic, we have developed a model of repeated tDCS in mice and used it to validate its effectiveness in relieving nicotine addiction. Anodal repeated tDCS was applied over the frontal cortex of Swiss female mice. The stimulation electrode (anode) was fixed directly onto the cranium, and the reference electrode was placed onto the ventral thorax. A 2 × 20 min/day stimulation paradigm for five consecutive days was used (0.2 mA). In the first study, we screened for behaviors altered by the stimulation. Second, we tested whether tDCS could alleviate abnormal behaviors associated with abstinence from nicotine consumption. In naive animals, repeated tDCS had antidepressant-like properties 3 weeks after the last stimulation, improved working memory, and decreased conditioned place preference for nicotine without affecting locomotor activity and anxiety-related behavior. Importantly, abnormal behaviors associated with chronic nicotine exposure (ie, depression-like behavior, increase in nicotine-induced place preference) were normalized by repeated tDCS. Our data show for the first time in an animal model that repeated tDCS is a promising, non-expensive clinical tool that could be used to reduce smoking craving and facilitate smoking cessation. Our animal model will be useful to investigate the mechanisms underlying the effects of tDCS on addiction and other psychiatric disorders.

OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury.

PubMed

Fazal, Nadeem

2013-01-01

Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury.

OX62+OX6+OX35+ rat dendritic cells are unable to prime CD4+ T cells for an effective immune response following acute burn injury☆

PubMed Central

Fazal, Nadeem

2013-01-01

Co-stimulatory molecules expressed on Dendritic Cells (DCs) function to coordinate an efficient immune response by T cells in the peripheral lymph nodes. We hypothesized that CD4+ T cell-mediated immune suppression following burn injury may be related to dysfunctional DCs residing in gut associated lymphoid tissues (GALT), such as Mesenteric Lymph Nodes (MLN). Therefore, we studied co-stimulatory molecules expressed on burn rat MLN DCs as an index of functional DCs that would mount an effective normal CD4+ T cell immune response. In a rat model of 30% Total Body Surface Area (TBSA) scald burn, OX62+OX6+OX35+ DCs and CD4+ T cells were isolated from MLN of day 3 post-burn and sham control rats. DCs were tested for their expression of co-stimulatory molecules, and prime CD4+ T cell (DC:CD4+T cell co-culture assays) to determine an effector immune response such as CD4+ T cell proliferation. The surface receptor expressions of MLN DCs co-stimulatory molecules, i.e., MHC-II, CD40, CD80 (B7-1), and CD86 (B7-2) were determined by Flow cytometry (quantitatively) and confocal microscopy (qualitatively). Tritiated thymidine and CFDA-SE determined CD4+ T cell proliferation following co-incubation with DCs. Cytokine milieu of MLN (IL-12 and IL-10) was assessed by mRNA determination by RT-PCR. The results showed down-regulated expressions of co-stimulatory markers (CD80, CD86, CD40 and MHC-II) of MLN DCs obtained from burn-injured rats, as well as lack of ability of these burn-induced DCs to stimulate CD4+ T cell proliferation in co-culture assays, as compared to the sham rats. Moreover, anti-CD40 stimulation of affected burn MLN DCs did not reverse this alteration. Furthermore, a marked up-regulation of mRNA IL-10 and down-regulation of mRNA IL-12 in burn MLN as compared to sham animals was also observed. To surmise, the data indicated that dysfunctional OX62+OX6+OX35+ rat MLN DCs may contribute to CD4+ T-cell-mediated immune suppression observed following acute burn injury. PMID:24600560

Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

PubMed Central

Luo, Shasha; Zou, Qiang

2016-01-01

It is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG-) specific experimental autoimmune encephalomyelitis (EAE) model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS). Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT) disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs). Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS. PMID:28070525

NASA Tech Briefs, February 2006

NASA Technical Reports Server (NTRS)

2006-01-01

Topics discussed include: Nearly Direct Measurement of Relative Permittivity; DCS-Neural-Network Program for Aircraft Control and Testing; Dielectric Heaters for Testing Spacecraft Nuclear Reactors; Using Doppler Shifts of GPS Signals To Measure Angular Speed; Monitoring Temperatures of Tires Using Luminescent Materials; Highly Efficient Multilayer Thermoelectric Devices; Very High-Speed Digital Video Capability for In-Flight Use; MMIC DHBT Common-Base Amplifier for 172 GHz; Modular, Microprocessor-Controlled Flash Lighting System; Generic Environment for Simulating Launch Operations; Modular Aero-Propulsion System Simulation; X-Windows Socket Widget Class; Infrastructure for Rapid Development of Java GUI Programs; Processing Raman Spectra of High-Pressure Hydrogen Flames; X-Windows Information Sharing Protocol Widget Class; Simulating Humans as Integral Parts of Spacecraft Missions; Analyzing Power Supply and Demand on the ISS; Polyimides From a-BPDA and Aromatic Diamines; Making Plant-Support Structures From Waste Plant Fiber; Large Deployable Reflectarray Antenna; Periodically Discharging, Gas-Coalescing Filter; Ion Milling On Steps for Fabrication of Nanowires; Neuro-Prosthetic Implants With Adjustable Electrode Arrays; Microfluidic Devices for Studying Biomolecular Interactions; Studying Functions of All Yeast Genes Simultaneously; Polarization Phase-Compensating Coats for Metallic Mirrors; Tunable-Bandwidth Filter System; Methodology for Designing Fault-Protection Software; and Ground-Based Localization of Mars Rovers.

Brain Switches Utilitarian Behavior: Does Gender Make the Difference?

PubMed Central

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

2010-01-01

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

Effects of psychosocial work factors on lifestyle changes: a cohort study.

PubMed

Allard, Karin Olofsson; Thomsen, Jane Frølund; Mikkelsen, Sigurd; Rugulies, Reiner; Mors, Ole; Kærgaard, Anette; Kolstad, Henrik A; Kaerlev, Linda; Andersen, Johan Hviid; Hansen, Ase Marie; Bonde, Jens Peter

2011-12-01

To evaluate the effect of the demand-control-support model, the effort-reward imbalance model, and emotional demands on smoking, alcohol consumption, physical activity, and body mass index. This is a 2-year prospective cohort study of 3224 public sector employees. Measures were assessed with questionnaires. Multiple regression analyses were used to predict changes in lifestyle factors. Low reward predicted smoking, low-decision latitude predicted being inactive, and high demands predicted high-alcohol consumption but only for men at follow-up even after controlling for potential confounders. There were no other significant findings in the expected direction except for some of the confounders. We found only limited and inconsistent support for the hypothesis that a poor psychosocial work environment is associated with an adverse lifestyle.

The demand control model and circadian saliva cortisol variations in a Swedish population based sample (The PART study)

PubMed Central

Alderling, Magnus; Theorell, Töres; de la Torre, Bartolomé; Lundberg, Ingvar

2006-01-01

Background Previous studies of the relationship between job strain and blood or saliva cortisol levels have been small and based on selected occupational groups. Our aim was to examine the association between job strain and saliva cortisol levels in a population-based study in which a number of potential confounders could be adjusted for. Methods The material derives from a population-based study in Stockholm on mental health and its potential determinants. Two data collections were performed three years apart with more than 8500 subjects responding to a questionnaire in both waves. In this paper our analyses are based on 529 individuals who held a job, participated in both waves as well as in an interview linked to the second wave. They gave saliva samples at awakening, half an hour later, at lunchtime and before going to bed on a weekday in close connection with the interview. Job control and job demands were assessed from the questionnaire in the second wave. Mixed models were used to analyse the association between the demand control model and saliva cortisol. Results Women in low strain jobs (high control and low demands) had significantly lower cortisol levels half an hour after awakening than women in high strain (low control and high demands), active (high control and high demands) or passive jobs (low control and low demands). There were no significant differences between the groups during other parts of the day and furthermore there was no difference between the job strain, active and passive groups. For men, no differences were found between demand control groups. Conclusion This population-based study, on a relatively large sample, weakly support the hypothesis that the demand control model is associated with saliva cortisol concentrations. PMID:17129377

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

PubMed

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

2013-09-27

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

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

PubMed Central

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

2005-01-01

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

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

PubMed

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.

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

PubMed Central

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

2018-01-01

BACKGROUND 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. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. PMID:25547776

Ebola virus infection induces irregular dendritic cell gene expression.

PubMed

Melanson, Vanessa R; Kalina, Warren V; Williams, Priscilla

2015-02-01

Filoviruses subvert the human immune system in part by infecting and replicating in dendritic cells (DCs). Using gene arrays, a phenotypic profile of filovirus infection in human monocyte-derived DCs was assessed. Monocytes from human donors were cultured in GM-CSF and IL-4 and were infected with Ebola virus Kikwit variant for up to 48 h. Extracted DC RNA was analyzed on SuperArray's Dendritic and Antigen Presenting Cell Oligo GEArray and compared to uninfected controls. Infected DCs exhibited increased expression of cytokine, chemokine, antiviral, and anti-apoptotic genes not seen in uninfected controls. Significant increases of intracellular antiviral and MHC I and II genes were also noted in EBOV-infected DCs. However, infected DCs failed to show any significant difference in co-stimulatory T-cell gene expression from uninfected DCs. Moreover, several chemokine genes were activated, but there was sparse expression of chemokine receptors that enabled activated DCs to home to lymph nodes. Overall, statistically significant expression of several intracellular antiviral genes was noted, which may limit viral load but fails to stop replication. EBOV gene expression profiling is of vital importance in understanding pathogenesis and devising novel therapeutic treatments such as small-molecule inhibitors.

Why the long hours? Job demands and social exchange dynamics.

PubMed

Genin, Emilie; Haines, Victor Y; Pelletier, David; Rousseau, Vincent; Marchand, Alain

2016-11-22

This study investigates the determinants of long working hours from the perspectives of the demand-control model [Karasek, 1979] and social exchange theory [Blau, 1964; Goulder, 1960]. These two theoretical perspectives are tested to understand why individuals work longer (or shorter) hours. The hypotheses are tested with a representative sample of 1,604 employed Canadians. In line with Karasek's model, the results support that high job demands are positively associated with longer work hours. The social exchange perspective would predict a positive association between skill discretion and work hours. This hypothesis was supported for individuals with a higher education degree. Finally, the results support a positive association between active jobs and longer work hours. Our research suggests that job demands and social exchange dynamics need to be considered together in the explanation of longer (or shorter) work hours.

The role of sleep disturbances in the longitudinal relationship between psychosocial working conditions, measured by work demands and support, and depression.

PubMed

Magnusson Hanson, Linda L; Chungkham, Holendro Singh; Åkerstedt, Torbjörn; Westerlund, Hugo

2014-12-01

Because work demands and lack of social support seem to be prospectively linked to sleep problems, and sleep problems are linked to depression, sleep problems may play a role in the relationship between these work characteristics and depressive symptoms. In order to shed more light on this relationship, the current study investigated whether disturbed sleep is a mediator in the longitudinal relationships between work demands, social support, and depression. Longitudinal cohort study with repeated survey measures on four occasions. Swedish workforce. 2,017 working participants from the Swedish Longitudinal Occupational Survey of Health in 2006, 2008, 2010, and 2012. Work demands (four items) and social support (six items) were assessed with the Demand Control Questionnaire, disturbed sleep (four items) with the Karolinska Sleep Questionnaire, and depressive symptoms with a brief subscale (six items) from the Symptom Checklist. Autoregressive longitudinal mediation models using structural equation modeling were tested. The work characteristics, and disturbed sleep, were found to be separately associated with depressive symptoms in subsequent waves. However, only demands were found to be longitudinally related to subsequent disturbed sleep. The longitudinal autoregressive models supported a weak mediating role of disturbed sleep in the relationship between demands and depressive symptoms (standardized beta 0.008, P < 0.001), but not between support and depressive symptoms. These results indicate that higher demands at work might cause an increase in depressive symptoms, in part, by increasing disturbed sleep, although the mediated effect was relatively small compared to the total effect. © 2014 Associated Professional Sleep Societies, LLC.

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

PubMed

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

2017-08-01

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

Work stress models and diurnal cortisol variations: The SALVEO study.

PubMed

Marchand, Alain; Juster, Robert-Paul; Durand, Pierre; Lupien, Sonia J

2016-04-01

The objective of this study was to assess components, subscales, and interactions proposed by the popular Job Demand-Control (JDC), Job Demand-Control-Support (JDCS), and Effort-Reward Imbalance (ERI) work stress models in relation to diurnal variation of the stress hormone cortisol. Participants included 401 day-shift workers employed from a random sampling of 34 Canadian workplaces. Questionnaires included the Job Content Questionnaire to measure psychological demands, decision latitude, and social support as well as the Effort-Reward Imbalance Questionnaire to measure effort, reward, and overcommitment. Salivary cortisol was collected on 2 working days at awaking, +30 min after awaking, 1400h, 1600h, and bedtime. Multilevel regressions with 3 levels (time of day, workers, workplaces) were performed. Results revealed that JDC, JDCS and ERI interactions were not statistically associated with variations in diurnal cortisol concentrations. By contrast when assessing specific work stress subscales, increased psychological demands were linked to decreased bedtime cortisol, increased job recognition was linked to increased cortisol +30 min after waking and at bedtime, and finally increased overcommitment was linked to increased awakening cortisol and decreased cortisol at 1400h, 1600h, and bedtime. Sex moderation effects principally among men were additionally detected for psychological demands, total social support, and supervisor support. Our findings suggest that components and subsubscales of these popular work stress models rather than theorized interactions are more meaningful in explaining diurnal cortisol variations. In particular, psychological demands, job recognition, overcommitment, and to a lesser extent social support at work are the most significant predictors of diurnal cortisol variation in this large sample of Canadian workers. Importantly, the overall effect sizes of these subscales that explained diurnal cortisol concentrations were weak. (c) 2016 APA, all rights reserved).

Different Expression of Interferon-Stimulated Genes in Response to HIV-1 Infection in Dendritic Cells Based on Their Maturation State

PubMed Central

Calonge, Esther; Bermejo, Mercedes; Diez-Fuertes, Francisco; Mangeot, Isabelle; González, Nuria; Coiras, Mayte; Jiménez Tormo, Laura; García-Perez, Javier; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

2017-01-01

ABSTRACT Dendritic cells (DCs) are professional antigen-presenting cells whose functions are dependent on their degree of differentiation. In their immature state, DCs capture pathogens and migrate to the lymph nodes. During this process, DCs become resident mature cells specialized in antigen presentation. DCs are characterized by a highly limiting environment for human immunodeficiency virus type 1 (HIV-1) replication due to the expression of restriction factors such as SAMHD1 and APOBEC3G. However, uninfected DCs capture and transfer viral particles to CD4 lymphocytes through a trans-enhancement mechanism in which chemokines are involved. We analyzed changes in gene expression with whole-genome microarrays when immature DCs (IDCs) or mature DCs (MDCs) were productively infected using Vpx-loaded HIV-1 particles. Whereas productive HIV infection of IDCs induced expression of interferon-stimulated genes (ISGs), such induction was not produced in MDCs, in which a sharp decrease in ISG- and CXCR3-binding chemokines was observed, lessening trans-infection of CD4 lymphocytes. Similar patterns of gene expression were found when DCs were infected with HIV-2 that naturally expresses Vpx. Differences were also observed under conditions of restrictive HIV-1 infection, in the absence of Vpx. ISG expression was not modified in IDCs, whereas an increase of ISG- and CXCR3-binding chemokines was observed in MDCs. Overall these results suggest that sensing and restriction of HIV-1 infection are different in IDCs and MDCs. We propose that restrictive infection results in increased virulence through different mechanisms. In IDCs avoidance of sensing and induction of ISGs, whereas in MDCs increased production of CXCR3-binding chemokines, would result in lymphocyte attraction and enhanced infection at the immune synapse. IMPORTANCE In this work we describe for the first time the activation of a different genetic program during HIV-1 infection depending on the state of maturation of DCs. This represents a breakthrough in the understanding of the restriction to HIV-1 infection of DCs. The results show that infection of DCs by HIV-1 reprograms their gene expression pattern. In immature cells, productive HIV-1 infection activates interferon-related genes involved in the control of viral replication, thus inducing an antiviral state in surrounding cells. Paradoxically, restriction of HIV-1 by SAMHD1 would result in lack of sensing and IFN activation, thus favoring initial HIV-1 escape from the innate immune response. In mature DCs, restrictive infection results in HIV-1 sensing and induction of ISGs, in particular CXCR3-binding chemokines, which could favor the transmission of HIV to lymphocytes. Our data support the hypothesis that genetic DC reprograming by HIV-1 infection favors viral escape and dissemination, thus increasing HIV-1 virulence. PMID:28148784

A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders.

PubMed

Minshawi, Noha F; Wink, Logan K; Shaffer, Rebecca; Plawecki, Martin H; Posey, David J; Liu, Hai; Hurwitz, Sarah; McDougle, Christopher J; Swiezy, Naomi B; Erickson, Craig A

2016-01-01

Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. ClinicalTrials.govNCT01086475.

Regulatory Dendritic Cells.

PubMed

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

2017-01-01

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

Empirical models for use in designing decompression procedures for space operations

NASA Technical Reports Server (NTRS)

Conkin, Johnny; Edwards, Benjamin F.; Waligora, James M.; Horrigan, David J., Jr.

1987-01-01

Empirical models for predicting the incidence of Type 1 altitude decompression sickness (DCS) and venous gas emboli (VGE) during space extravehicular activity (EVA), and for use in designing safe denitrogenation decompression procedures are developed. The models are parameterized using DCS and VGE incidence data from NASA and USAF manned altitude chamber decompression tests using 607 male and female subject tests. These models, and procedures for their use, consist of: (1) an exponential relaxation model and procedure for computing tissue nitrogen partial pressure resulting from a specified prebreathing and stepped decompression sequence; (2) a formula for calculating Tissue Ratio (TR), a tissue decompression stress index; (3) linear and Hill equation models for predicting the total incidence of VGE and DCS attendant with a particular TR; (4) graphs of cumulative DCS and VGE incidence (risk) versus EVA exposure time at any specified TR; and (5) two equations for calculating the average delay period for the initial detection of VGE or indication of Type 1 DCS in a group after a specific denitrogenation decompression procedure. Several examples of realistic EVA preparations are provided.

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

PubMed

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

2015-09-01

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

Contralesional Cathodal versus Dual Transcranial Direct Current Stimulation for Decreasing Upper Limb Spasticity in Chronic Stroke Individuals: A Clinical and Neurophysiological Study.

PubMed

Del Felice, Alessandra; Daloli, Verena; Masiero, Stefano; Manganotti, Paolo

2016-12-01

Different transcranial direct current stimulation (tDCS) paradigms have been implemented to treat poststroke spasticity, but discordant results have been reported. This study aimed to determine the efficacy and persistence of dual tDCS (anode over affected motor cortex [M1] and cathode over contralateral M1) compared with cathodal tDCS (cathode over contralateral M1) on upper limb (UL) functional, behavioral, and neurophysiological measures in chronic poststroke individuals. Ten subjects with UL spasticity (7 men; mean 62 years; 8 ischemic stroke; years from event: 2.3 years) were enrolled in a cross-over, double-blinded study. Cathodal and dual tDCS, both preceded by 1 week of sham stimulation 1 month before real stimulation, were applied with 3 months interval. Stimulating paradigm was 20 minutes for five consecutive days in each block. Evaluations were performed before (T1), after real or sham treatment (T2), and after 1 (T3), 4 (T4), and 8 weeks (T5). Functional, behavioral, and neurophysiological tests were performed at each time. Both tDCS paradigms decreased spasticity, increased strength, and ameliorated behavioral scales. Cathodal tDCS was superior to dual tDCS in reducing UL distal spasticity immediately after treatment (T2: cathodal > dual: P = .023) and provided a higher and longer lasting reduction at proximal districts (T3: cathodal > dual: P = .042; T4: cathodal > dual: P = .028; T5: cathodal > dual: P = .05). These findings are supported by an H-reflex modulation (overall time effect P > .002). Cathodal tDCS is slightly more effective than dual tDCS in reducing distal UL spasticity in chronic poststroke subjects. A modulation of spinal inhibitory mechanisms, demonstrated by H-reflex modifications, supports this finding. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Sham transcranial electrical stimulation and its effects on corticospinal excitability: a systematic review and meta-analysis.

PubMed

Dissanayaka, Thusharika D; Zoghi, Maryam; Farrell, Michael; Egan, Gary F; Jaberzadeh, Shapour

2018-02-23

Sham stimulation is used in randomized controlled trials (RCTs) to assess the efficacy of active stimulation and placebo effects. It should mimic the characteristics of active stimulation to achieve blinding integrity. The present study was a systematic review and meta-analysis of the published literature to identify the effects of sham transcranial electrical stimulation (tES) - including anodal and cathodal transcranial direct current stimulation (a-tDCS, c-tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) - on corticospinal excitability (CSE), compared to baseline in healthy individuals. Electronic databases - PubMed, CINAHL, Scopus, Science Direct and MEDLINE (Ovid) - were searched for RCTs of tES from 1990 to March 2017. Thirty RCTs were identified. Using a random-effects model, meta-analysis of a-tDCS, c-tDCS, tACS, tRNS and tPCS studies showed statistically non-significant pre-post effects of sham interventions on CSE. This review found evidence for statically non-significant effects of sham tES on CSE.

Extraction, -scrub, -strip test results from the interim salt disposition program macrobatch 10 tank 21H qualification samples

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

Peters, T. B.

Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Macrobatch (Salt Batch) 10 for the Interim Salt Disposition Program (ISDP). The Salt Batch 10 characterization results were previously reported.ii,iii An Extraction, -Scrub, -Strip (ESS) test was performed to determine cesium distribution ratios (D(Cs)) and cesium concentration in the strip effluent (SE) and decontaminated salt solution (DSS) streams; this data will be used by Tank Farm Engineering to project a cesium decontamination factor (DF). This test used actual Tank 21H material, and a sample of the NGS Blend solvent currently being used at the Modularmore » Caustic-Side Solvent Extraction Unit (MCU). The ESS test showed acceptable performance with an extraction D(Cs) value of 110. This value is consistent with results from previous salt batch ESS tests using similar solvent formulations. This is better than the predicted value of 39.8 from a recently created D(Cs) model.« less

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

PubMed Central

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

2016-01-01

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

Lead effects on development and function of bone marrow-derived dendritic cells promote Th2 immune responses

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

Gao Donghong; Mondal, Tapan K.; Lawrence, David A.

2007-07-01

Although lead (Pb) has significant effects on the development and function of macrophages, B cells, and T cells and has been suggested to promote allergic asthma in mice and humans, Pb modulation of bone marrow (BM)-derived dendritic cells (DCs) and the resultant DC effects on Th1 and Th2 development have not been examined. Accordingly, we cultured BM cells with murine granulocyte macrophage-colony stimulating factor (mGM-CSF) {+-} PbCl{sub 2}. At day 10, culture supernatant (SN) and non-adherent cells were harvested for analysis. Additionally, day 10 non-adherent BM-DCs were harvested and recultured with mGM-CSF + LPS {+-} Pb for 2 days. Themore » day 10 Pb exposure significantly inhibited BM-DC generation, based on CD11c expression. Although fewer DCs were generated with Pb, the existing Pb-exposed DCs had significantly greater MHC-II expression than did the non-Pb-exposed DCs. However, these differences diminished upon LPS stimulation. After LPS stimulation, CD80, CD86, CD40, CD54, and MHC-II were all up-regulated on both Pb-DCs and DCs, but Pb-DCs expressed significantly less CD80 than did DCs. The CD86:CD80 ratio suggests a Pb-DC potential for Th2 cell development. After LPS stimulation, IL-6, IL-10, IL-12 (p70), and TNF-{alpha} levels significantly increased with both Pb-DCs and DCs, but Pb-DCs produced significantly less cytokines than did DCs, except for IL-10, which further supports Pb-DC preferential skewing toward type-2 immunity. In vitro studies confirm that Pb-DCs have the ability to polarize antigen-specific T cells to Th2 cells. Pb-DCs also enhanced allogeneic and autologous T cell proliferation in vitro, and in vivo studies suggested that Pb-DCs inhibited Th1 effects on humoral and cell-mediated immunity. The Pb effect was mainly on DCs, rather than on T cells, and Pb's modification of DC function appears to be the main cause of Pb's promotion of type-2-related immunity, which may relate to Pb's enhanced activation of the Erk/MAP kinase pathway.« less

Decompression models: review, relevance and validation capabilities.

PubMed

Hugon, J

2014-01-01

For more than a century, several types of mathematical models have been proposed to describe tissue desaturation mechanisms in order to limit decompression sickness. These models are statistically assessed by DCS cases, and, over time, have gradually included bubble formation biophysics. This paper proposes to review this evolution and discuss its limitations. This review is organized around the comparison of decompression model biophysical criteria and theoretical foundations. Then, the DCS-predictive capability was analyzed to assess whether it could be improved by combining different approaches. Most of the operational decompression models have a neo-Haldanian form. Nevertheless, bubble modeling has been gaining popularity, and the circulating bubble amount has become a major output. By merging both views, it seems possible to build a relevant global decompression model that intends to simulate bubble production while predicting DCS risks for all types of exposures and decompression profiles. A statistical approach combining both DCS and bubble detection databases has to be developed to calibrate a global decompression model. Doppler ultrasound and DCS data are essential: i. to make correlation and validation phases reliable; ii. to adjust biophysical criteria to fit at best the observed bubble kinetics; and iii. to build a relevant risk function.

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

PubMed

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

2016-06-01

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

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

PubMed Central

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

2015-01-01

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

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

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

Jacques Hugo; Ronald Boring; Lew Hanes

2013-09-01

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

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

PubMed

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.

Modulation of frontal effective connectivity during speech.

PubMed

Holland, Rachel; Leff, Alex P; Penny, William D; Rothwell, John C; Crinion, Jenny

2016-10-15

Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2012-09-15

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

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

PubMed

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

2016-01-15

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

Validation of diffuse correlation spectroscopy sensitivity to nicotinamide-induced blood flow elevation in the murine hindlimb using the fluorescent microsphere technique

NASA Astrophysics Data System (ADS)

Proctor, Ashley R.; Ramirez, Gabriel A.; Han, Songfeng; Liu, Ziping; Bubel, Tracy M.; Choe, Regine

2018-03-01

Nicotinamide has been shown to affect blood flow in both tumor and normal tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was used as a simple intervention to test the sensitivity of noninvasive diffuse correlation spectroscopy (DCS) to changes in blood flow in the murine left quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard fluorescent microsphere (FM) technique for validation. The nicotinamide dose-response experiment showed that relative blood flow measured by DCS increased following treatment with 500- and 1000-mg / kg nicotinamide. The DCS and FM technique comparison showed that blood flow index measured by DCS was correlated with FM counts quantified by image analysis. The results of this study show that DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left quadriceps femoris. Additionally, the results of the comparison were consistent with similar studies in higher-order animal models, suggesting that mouse models can be effectively employed to investigate the utility of DCS for various blood flow measurement applications.

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool.

PubMed

Del Felice, Alessandra; Magalini, Alessandra; Masiero, Stefano

2015-01-01

Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

PubMed

Macedo, I C; de Oliveira, C; Vercelino, R; Souza, A; Laste, G; Medeiros, L F; Scarabelot, V L; Nunes, E A; Kuo, J; Fregni, F; Caumo, W; Torres, I L S

2016-08-01

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 μA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 μA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation. Copyright © 2016. Published by Elsevier Ltd.

Minocycline promotes the generation of dendritic cells with regulatory properties.

PubMed

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

2016-08-16

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

Electric Water Heater Modeling and Control Strategies for Demand Response

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

Diao, Ruisheng; Lu, Shuai; Elizondo, Marcelo A.

2012-07-22

Abstract— Demand response (DR) has a great potential to provide balancing services at normal operating conditions and emergency support when a power system is subject to disturbances. Effective control strategies can significantly relieve the balancing burden of conventional generators and reduce investment on generation and transmission expansion. This paper is aimed at modeling electric water heaters (EWH) in households and tests their response to control strategies to implement DR. The open-loop response of EWH to a centralized signal is studied by adjusting temperature settings to provide regulation services; and two types of decentralized controllers are tested to provide frequency supportmore » following generator trips. EWH models are included in a simulation platform in DIgSILENT to perform electromechanical simulation, which contains 147 households in a distribution feeder. Simulation results show the dependence of EWH response on water heater usage . These results provide insight suggestions on the need of control strategies to achieve better performance for demand response implementation. Index Terms— Centralized control, decentralized control, demand response, electrical water heater, smart grid« less

Cigarette smoke-induced chronic obstructive pulmonary disease is attenuated by CCL20-blocker: a rat model.

PubMed

Sun, Desheng; Ouyang, Yao; Gu, Yanhui; Liu, Xiansheng

2016-08-31

To evaluate whether the effect of dendritic cells (DCs) on chronic obstructive pulmonary disease (COPD) can be relieved by blocking CCL20. 30 Wistar rats were randomly divided into three groups: control, COPD, and COPD treated with CCL20 monoclonal antibody. In the latter two groups, COPD was induced by four-week cigarette smoke exposure and trachea injection of lipopolysaccharide solution on two occasions. CCL20 monoclonal antibody was injected intraperitoneally on the first day. All animals were sacrificed on the 29th day. Pathomorphology of the lung and bronchiole was analyzed using hematoxylin and eosin staining. The CCR6 content in the bronchoalveolar lavage fluid was detected using ELISA. DC distribution in the lung was examined by immunohistochemistry for OX62. COPD rat models showed pathological alterations similar to those in COPD patients. DCs, CCR6, and the severity of emphysema were significantly increased in the COPD group than in controls (all P values <0.001), and they were significantly reduced after anti-CCL20 treatment compared with the COPD group (all P values <0.05). The interaction between CCR6 and its ligand CCL20 promotes the effect of DCs in the COPD pathogenesis, which can be reduced by blocking CCL20.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-08-01

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

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

PubMed

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

2015-12-01

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

Factor structure and longitudinal measurement invariance of the demand control support model: an evidence from the Swedish Longitudinal Occupational Survey of Health (SLOSH).

PubMed

Chungkham, Holendro Singh; Ingre, Michael; Karasek, Robert; Westerlund, Hugo; Theorell, Töres

2013-01-01

To examine the factor structure and to evaluate the longitudinal measurement invariance of the demand-control-support questionnaire (DCSQ), using the Swedish Longitudinal Occupational Survey of Health (SLOSH). A confirmatory factor analysis (CFA) and multi-group confirmatory factor analysis (MGCFA) models within the framework of structural equation modeling (SEM) have been used to examine the factor structure and invariance across time. Four factors: psychological demand, skill discretion, decision authority and social support, were confirmed by CFA at baseline, with the best fit obtained by removing the item repetitive work of skill discretion. A measurement error correlation (0.42) between work fast and work intensively for psychological demands was also detected. Acceptable composite reliability measures were obtained except for skill discretion (0.68). The invariance of the same factor structure was established, but caution in comparing mean levels of factors over time is warranted as lack of intercept invariance was evident. However, partial intercept invariance was established for work intensively. Our findings indicate that skill discretion and decision authority represent two distinct constructs in the retained model. However removing the item repetitive work along with either work fast or work intensively would improve model fit. Care should also be taken while making comparisons in the constructs across time. Further research should investigate invariance across occupations or socio-economic classes.

Factor Structure and Longitudinal Measurement Invariance of the Demand Control Support Model: An Evidence from the Swedish Longitudinal Occupational Survey of Health (SLOSH)

PubMed Central

Chungkham, Holendro Singh; Ingre, Michael; Karasek, Robert; Westerlund, Hugo; Theorell, Töres

2013-01-01

Objectives To examine the factor structure and to evaluate the longitudinal measurement invariance of the demand-control-support questionnaire (DCSQ), using the Swedish Longitudinal Occupational Survey of Health (SLOSH). Methods A confirmatory factor analysis (CFA) and multi-group confirmatory factor analysis (MGCFA) models within the framework of structural equation modeling (SEM) have been used to examine the factor structure and invariance across time. Results Four factors: psychological demand, skill discretion, decision authority and social support, were confirmed by CFA at baseline, with the best fit obtained by removing the item repetitive work of skill discretion. A measurement error correlation (0.42) between work fast and work intensively for psychological demands was also detected. Acceptable composite reliability measures were obtained except for skill discretion (0.68). The invariance of the same factor structure was established, but caution in comparing mean levels of factors over time is warranted as lack of intercept invariance was evident. However, partial intercept invariance was established for work intensively. Conclusion Our findings indicate that skill discretion and decision authority represent two distinct constructs in the retained model. However removing the item repetitive work along with either work fast or work intensively would improve model fit. Care should also be taken while making comparisons in the constructs across time. Further research should investigate invariance across occupations or socio-economic classes. PMID:23950957

Transcranial direct current stimulation in post stroke aphasia and primary progressive aphasia: Current knowledge and future clinical applications.

PubMed

Sebastian, Rajani; Tsapkini, Kyrana; Tippett, Donna C

2016-06-13

The application of transcranial direct current stimulation (tDCS) in chronic post stroke aphasia is documented in a substantial literature, and there is some new evidence that tDCS can augment favorable language outcomes in primary progressive aphasia. Anodal tDCS is most often applied to the left hemisphere language areas to increase cortical excitability (increase the threshold of activation) and cathodal tDCS is most often applied to the right hemisphere homotopic areas to inhibit over activation in contralesional right homologues of language areas. Outcomes usually are based on neuropsychological and language test performance, following a medical model which emphasizes impairment of function, rather than a model which emphasizes functional communication. In this paper, we review current literature of tDCS as it is being used as a research tool, and discuss future implementation of tDCS as an adjuvant treatment to behavioral speech-language pathology intervention. We review literature describing non-invasive brain stimulation, the mechanism of tDCS, and studies of tDCS in aphasia and neurodegenerative disorders. We discuss future clinical applications. tDCS is a promising adjunct to traditional speech-language pathology intervention to address speech-language deficits after stroke and in the neurodegenerative disease, primary progressive aphasia. Limited data are available regarding how performance on these types of specific tasks translates to functional communication outcomes.

Transcranial Direct Current Stimulation in Post Stroke Aphasia and Primary Progressive Aphasia: Current Knowledge and Future Clinical Applications

PubMed Central

Sebastian, Rajani; Tsapkini, Kyrana; Tippett, Donna C.

2016-01-01

BACKGROUND The application of transcranial direct current stimulation (tDCS) in chronic post stroke aphasia is documented in a substantial literature, and there is some new evidence that tDCS can augment favorable language outcomes in primary progressive aphasia. Anodal tDCS is most often applied to the left hemisphere language areas to increase cortical excitability (increase the threshold of activation) and cathodal tDCS is most often applied to the right hemisphere homotopic areas to inhibit over activation in contralesional right homologues of language areas. Outcomes usually are based on neuropsychological and language test performance, following a medical model which emphasizes impairment of function, rather than a model which emphasizes functional communication. OBJECTIVE In this paper, we review current literature of tDCS as it is being used as a research tool, and discuss future implementation of tDCS as an adjuvant treatment to behavioral speech-language pathology intervention. METHODS We review literature describing non-invasive brain stimulation, the mechanism of tDCS, and studies of tDCS in aphasia and neurodegenerative disorders. We discuss future clinical applications. RESULTS/CONCLUSIONS tDCS is a promising adjunct to traditional speech-language pathology intervention to address speech-language deficits after stroke and in the neurodegenerative disease, primary progressive aphasia. Limited data are available regarding how performance on these types of specific tasks translates to functional communication outcomes. PMID:27314871

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

PubMed

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

2016-10-01

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

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

PubMed

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

2016-11-01

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

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

PubMed

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

2017-09-01

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

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data.

PubMed

Mataix-Cols, David; Fernández de la Cruz, Lorena; Monzani, Benedetta; Rosenfield, David; Andersson, Erik; Pérez-Vigil, Ana; Frumento, Paolo; de Kleine, Rianne A; Difede, JoAnn; Dunlop, Boadie W; Farrell, Lara J; Geller, Daniel; Gerardi, Maryrose; Guastella, Adam J; Hofmann, Stefan G; Hendriks, Gert-Jan; Kushner, Matt G; Lee, Francis S; Lenze, Eric J; Levinson, Cheri A; McConnell, Harry; Otto, Michael W; Plag, Jens; Pollack, Mark H; Ressler, Kerry J; Rodebaugh, Thomas L; Rothbaum, Barbara O; Scheeringa, Michael S; Siewert-Siegmund, Anja; Smits, Jasper A J; Storch, Eric A; Ströhle, Andreas; Tart, Candyce D; Tolin, David F; van Minnen, Agnes; Waters, Allison M; Weems, Carl F; Wilhelm, Sabine; Wyka, Katarzyna; Davis, Michael; Rück, Christian; Altemus, Margaret; Anderson, Page; Cukor, Judith; Finck, Claudia; Geffken, Gary R; Golfels, Fabian; Goodman, Wayne K; Gutner, Cassidy; Heyman, Isobel; Jovanovic, Tanja; Lewin, Adam B; McNamara, Joseph P; Murphy, Tanya K; Norrholm, Seth; Thuras, Paul

2017-05-01

Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

Technical Advance: Live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung

PubMed Central

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G.; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-01-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. PMID:24899587

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

PubMed

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

2013-02-01

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

Increasing honesty in humans with noninvasive brain stimulation

PubMed Central

Maréchal, Michel André; Cohn, Alain; Ugazio, Giuseppe

2017-01-01

Honesty plays a key role in social and economic interactions and is crucial for societal functioning. However, breaches of honesty are pervasive and cause significant societal and economic problems that can affect entire nations. Despite its importance, remarkably little is known about the neurobiological mechanisms supporting honest behavior. We demonstrate that honesty can be increased in humans with transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex. Participants (n = 145) completed a die-rolling task where they could misreport their outcomes to increase their earnings, thereby pitting honest behavior against personal financial gain. Cheating was substantial in a control condition but decreased dramatically when neural excitability was enhanced with tDCS. This increase in honesty could not be explained by changes in material self-interest or moral beliefs and was dissociated from participants’ impulsivity, willingness to take risks, and mood. A follow-up experiment (n = 156) showed that tDCS only reduced cheating when dishonest behavior benefited the participants themselves rather than another person, suggesting that the stimulated neural process specifically resolves conflicts between honesty and material self-interest. Our results demonstrate that honesty can be strengthened by noninvasive interventions and concur with theories proposing that the human brain has evolved mechanisms dedicated to control complex social behaviors. PMID:28396395

Field Evaluation of Detection-Control System

DOT National Transportation Integrated Search

2015-04-01

In this research, a field evaluation of the Detection-Control System (D-CS) was conducted at eight sites located in four States. D-CS is similar to a traditional advance detector system in that it uses information from detectors located upstream of t...

Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles

PubMed Central

Tu, Juan; Ha Hwang, Joo; Chen, Tao; Fan, Tingbo; Guo, Xiasheng; Crum, Lawrence A.; Zhang, Dong

2012-01-01

High intensity focused ultrasound (HIFU)-induced hyperthermia is a promising tool for cancer therapy. Three-dimensional nonlinear acoustic-bioheat transfer-blood flow-coupling model simulations and in vivo thermocouple measurements were performed to study hyperthermia effects in rabbit auricular vein exposed to pulsed HIFU (pHIFU) at varied duty cycles (DCs). pHIFU-induced temperature elevations are shown to increase with increasing DC. A critical DC of 6.9% is estimated for temperature at distal vessel wall exceeding 44 °C, although different tissue depths and inclusions could affect the DC threshold. The results demonstrate clinic potentials of achieving controllable hyperthermia by adjusting pHIFU DCs, while minimizing perivascular thermal injury. PMID:23112347

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

PubMed

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

2017-08-21

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

mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

PubMed

Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz; Loebbermann, Jens; Johnson, Matthew Joseph; Hakimpour, Paul; Hagan, Thomas; Benitez, Lydia; Todor, Andrei; Machiah, Deepa; Oriss, Timothy; Ray, Anuradha; Bosinger, Steven; Ravindran, Rajesh; Li, Shuzhao; Pulendran, Bali

2017-09-08

Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

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

NASA Technical Reports Server (NTRS)

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

1991-01-01

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

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

PubMed

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

2016-12-14

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

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

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

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

1996-01-01

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

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

PubMed Central

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

2017-01-01

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

Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: role of macrophage scavenger receptor class A type I and II.

PubMed

Ilchmann, Anne; Burgdorf, Sven; Scheurer, Stephan; Waibler, Zoe; Nagai, Ryoji; Wellner, Anne; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Henle, Thomas; Kurts, Christian; Kalinke, Ulrich; Vieths, Stefan; Toda, Masako

2010-01-01

The Maillard reaction occurs between reducing sugars and proteins during thermal processing of foods. It produces chemically glycated proteins termed advanced glycation end products (AGEs). The glycation structures of AGEs are suggested to function as pathogenesis-related immune epitopes in food allergy. This study aimed at defining the T-cell immunogenicity of food AGEs by using ovalbumin (OVA) as a model allergen. AGE-OVA was prepared by means of thermal processing of OVA in the presence of glucose. Activation of OVA-specific CD4(+) T cells by AGE-OVA was evaluated in cocultures with bone marrow-derived murine myeloid dendritic cells (mDCs) as antigen-presenting cells. The uptake mechanisms of mDCs for AGE-OVA were investigated by using inhibitors of putative cell-surface receptors for AGEs, as well as mDCs deficient for these receptors. Compared with the controls (native OVA and OVA thermally processed without glucose), AGE-OVA enhanced the activation of OVA-specific CD4(+) T cells on coculture with mDCs, indicating that the glycation of OVA enhanced the T-cell immunogenicity of the allergen. The mDC uptake of AGE-OVA was significantly higher than that of the controls. We identified scavenger receptor class A type I and II (SR-AI/II) as a mediator of the AGE-OVA uptake, whereas the receptor for AGEs and galectin-3 were not responsible. Importantly, the activation of OVA-specific CD4(+) T cells by AGE-OVA was attenuated on coculture with SR-AI/II-deficient mDCs. SR-AI/II targets AGE-OVA to the MHC class II loading pathway in mDCs, leading to an enhanced CD4(+) T-cell activation. The Maillard reaction might thus play an important role in the T-cell immunogenicity of food allergens. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Cerebellar tDCS Modulates Neural Circuits during Semantic Prediction: A Combined tDCS-fMRI Study.

PubMed

D'Mello, Anila M; Turkeltaub, Peter E; Stoodley, Catherine J

2017-02-08

It has been proposed that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. In language, semantic prediction speeds speech production and comprehension. Right cerebellar lobules VI and VII (including Crus I/II) are engaged during a variety of language processes and are functionally connected with cerebral cortical language networks. Further, right posterolateral cerebellar neuromodulation modifies behavior during predictive language processing. These data are consistent with a role for the cerebellum in semantic processing and semantic prediction. We combined transcranial direct current stimulation (tDCS) and fMRI to assess the behavioral and neural consequences of cerebellar tDCS during a sentence completion task. Task-based and resting-state fMRI data were acquired in healthy human adults ( n = 32; μ = 23.1 years) both before and after 20 min of 1.5 mA anodal ( n = 18) or sham ( n = 14) tDCS applied to the right posterolateral cerebellum. In the sentence completion task, the first four words of the sentence modulated the predictability of the final target word. In some sentences, the preceding context strongly predicted the target word, whereas other sentences were nonpredictive. Completion of predictive sentences increased activation in right Crus I/II of the cerebellum. Relative to sham tDCS, anodal tDCS increased activation in right Crus I/II during semantic prediction and enhanced resting-state functional connectivity between hubs of the reading/language networks. These results are consistent with a role for the right posterolateral cerebellum beyond motor aspects of language, and suggest that cerebellar internal models of linguistic stimuli support semantic prediction. SIGNIFICANCE STATEMENT Cerebellar involvement in language tasks and language networks is now well established, yet the specific cerebellar contribution to language processing remains unclear. It is thought that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. Here we combined neuroimaging and neuromodulation to provide evidence that the cerebellum is specifically involved in semantic prediction during sentence processing. We found that activation within right Crus I/II was enhanced when semantic predictions were made, and we show that modulation of this region with transcranial direct current stimulation alters both activation patterns and functional connectivity within whole-brain language networks. For the first time, these data show that cerebellar neuromodulation impacts activation patterns specifically during predictive language processing. Copyright © 2017 the authors 0270-6474/17/371604-10$15.00/0.

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

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

Yao, Pan; Hongqian, Chu; Qinghe, Meng

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

Hypothesis for cognitive effects of transcranial direct current stimulation: Externally- and internally-directed cognition.

PubMed

Greenwood, Pamela M; Blumberg, Eric J; Scheldrup, Melissa R

2018-03-01

A comprehensive explanation is lacking for the broad array of cognitive effects modulated by transcranial direct current stimulation (tDCS). We advanced the testable hypothesis that tDCS to the default mode network (DMN) increases processing of goals and stored information at the expense of external events. We further hypothesized that tDCS to the dorsal attention network (DAN) increases processing of external events at the expense of goals and stored information. A literature search (PsychINFO) identified 42 empirical studies and 3 meta-analyses examining effects of prefrontal and/or parietal tDCS on tasks that selectively required external and/or internal processing. Most, though not all, of the studies that met our search criteria supported our hypothesis. Three meta-analyses supported our hypothesis. The hypothesis we advanced provides a framework for the design and interpretation of results in light of the role of large-scale intrinsic networks that govern attention. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-08-01

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

Dendritic cells in transplantation and immune-based therapies.

PubMed

Young, James W; Merad, Miriam; Hart, Derek N J

2007-01-01

Dendritic cells (DCs) are specialized, bone marrow-derived leukocytes critical to the onset of both innate and adaptive immunity. The divisions of labor among distinct human DC subtypes achieve the most effective balance between steady-state tolerance and the induction of innate and adaptive immunity against pathogens, tumors, and other insults. Maintenance of tolerance in the steady state is an active process involving resting or semimature DCs. Breakdowns in this homeostasis can result in autoimmunity. Perturbation of the steady state should first lead to the onset of innate immunity mediated by rapid responders in the form of plasmacytoid and monocyte-derived DC stimulators and natural killer (NK) and NK T-cell responders. These innate effectors then provide additional inflammatory cytokines, including interferon-gamma, which support the activation and maturation of resident and circulating populations of DCs. These are critical to the onset and expansion of adaptive immunity, including Th1, Th2, and cytotoxic T-lymphocyte responses. Rodent models are now revealing important data about distinct DC precursors, homeostasis of tissue-resident DCs, and DC turnover in response to inflammation and pathological conditions like graft-versus-host disease. The use of defined DC subtypes to stimulate both innate and adaptive immunity, either in combination or in a prime-boost vaccine sequence, may prove most useful clinically by harnessing both effector cell compartments.

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

PubMed

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

2017-05-01

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

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

PubMed

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.

Fault detection of Tennessee Eastman process based on topological features and SVM

NASA Astrophysics Data System (ADS)

Zhao, Huiyang; Hu, Yanzhu; Ai, Xinbo; Hu, Yu; Meng, Zhen

2018-03-01

Fault detection in industrial process is a popular research topic. Although the distributed control system(DCS) has been introduced to monitor the state of industrial process, it still cannot satisfy all the requirements for fault detection of all the industrial systems. In this paper, we proposed a novel method based on topological features and support vector machine(SVM), for fault detection of industrial process. The proposed method takes global information of measured variables into account by complex network model and predicts whether a system has generated some faults or not by SVM. The proposed method can be divided into four steps, i.e. network construction, network analysis, model training and model testing respectively. Finally, we apply the model to Tennessee Eastman process(TEP). The results show that this method works well and can be a useful supplement for fault detection of industrial process.

Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

PubMed

Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

2016-01-01

Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

Increased B7-H1 expression on dendritic cells correlates with programmed death 1 expression on T cells in simian immunodeficiency virus-infected macaques and may contribute to T cell dysfunction and disease progression.

PubMed

Xu, Huanbin; Wang, Xiaolei; Pahar, Bapi; Moroney-Rasmussen, Terri; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2010-12-15

Suppression of dendritic cell (DC) function in HIV-1 infection is thought to contribute to inhibition of immune responses and disease progression, but the mechanism of this suppression remains undetermined. Using the rhesus macaque model, we show B7-H1 (programmed death [PD]-L1) is expressed on lymphoid and mucosal DCs (both myeloid DCs and plasmacytoid DCs), and its expression significantly increases after SIV infection. Meanwhile, its receptor, PD-1, is upregulated on T cells in both peripheral and mucosal tissues and maintained at high levels on SIV-specific CD8(+) T cell clones in chronic infection. However, both B7-H1 and PD-1 expression in SIV controllers was similar to that of controls. Expression of B7-H1 on both peripheral myeloid DCs and plasmacytoid DCs positively correlated with levels of PD-1 on circulating CD4(+) and CD8(+) T cells, viremia, and declining peripheral CD4(+) T cell levels in SIV-infected macaques. Importantly, blocking DC B7-H1 interaction with PD-1(+) T cells could restore SIV-specific CD4(+) and CD8(+) T cell function as evidenced by increased cytokine secretion and proliferative capacity. Combined, the results indicate that interaction of B7-H1-PD-1 between APCs and T cells correlates with impairment of CD4(+) Th cells and CTL responses in vivo, and all are associated with disease progression in SIV infection. Blockade of this pathway may have therapeutic implications for HIV-infected patients.

Job stress and job satisfaction: home care workers in a consumer-directed model of care.

PubMed

Delp, Linda; Wallace, Steven P; Geiger-Brown, Jeanne; Muntaner, Carles

2010-08-01

To investigate determinants of job satisfaction among home care workers in a consumer-directed model. Analysis of data collected from telephone interviews with 1,614 Los Angeles home care workers on the state payroll in 2003. Multivariate logistic regression analysis was used to determine the odds of job satisfaction using job stress model domains of demands, control, and support. Abuse from consumers, unpaid overtime hours, and caring for more than one consumer as well as work-health demands predict less satisfaction. Some physical and emotional demands of the dyadic care relationship are unexpectedly associated with greater job satisfaction. Social support and control, indicated by job security and union involvement, have a direct positive effect on job satisfaction. Policies that enhance the relational component of care may improve workers' ability to transform the demands of their job into dignified and satisfying labor. Adequate benefits and sufficient authorized hours of care can minimize the stress of unpaid overtime work, caring for multiple consumers, job insecurity, and the financial constraints to seeking health care. Results have implications for the structure of consumer-directed models of care and efforts to retain long-term care workers.

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

PubMed

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

2015-02-01

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

In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

PubMed Central

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

2015-01-01

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection. PMID:25658925

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2014-01-01

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

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

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

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

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

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

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

Pollet, J.

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-criticalmore » 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)« less

Epifluorescence Intravital Microscopy of Murine Corneal Dendritic Cells

PubMed Central

Rosenbaum, James T.; Planck, Stephen R.

2010-01-01

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

The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

PubMed

Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

2017-07-28

Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

IL-23 (Interleukin-23)-Producing Conventional Dendritic Cells Control the Detrimental IL-17 (Interleukin-17) Response in Stroke.

PubMed

Gelderblom, Mathias; Gallizioli, Mattia; Ludewig, Peter; Thom, Vivien; Arunachalam, Priyadharshini; Rissiek, Björn; Bernreuther, Christian; Glatzel, Markus; Korn, Thomas; Arumugam, Thiruma Valavan; Sedlacik, Jan; Gerloff, Christian; Tolosa, Eva; Planas, Anna M; Magnus, Tim

2018-01-01

Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels. We used conditional DC depletion, bone marrow chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further explore the functional role of DCs. We show that the ischemic brain was rapidly infiltrated by IRF4 + /CD172a + conventional type 2 DCs and that conventional type 2 DCs were the most abundant subset in comparison with all other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs became the major source of IL-23, promoting neutrophil infiltration by induction of IL-17 (interleukin-17) in γδ T cells. Functionally, the depletion of CD11c + cells or the genetic disruption of the IL-23 signaling abrogated both IL-17 production in γδ T cells and neutrophil infiltration. Interruption of the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome after stroke. Our results suggest a central role for interferon regulatory factor 4-positive IL-23-producing conventional DCs in the IL-17-dependent secondary tissue damage in stroke. © 2017 American Heart Association, Inc.

MERTK as negative regulator of human T cell activation

PubMed Central

Cabezón, Raquel; Carrera-Silva, E. Antonio; Flórez-Grau, Georgina; Errasti, Andrea E.; Calderón-Gómez, Elisabeth; Lozano, Juan José; España, Carolina; Ricart, Elena; Panés, Julián; Rothlin, Carla Vanina; Benítez-Ribas, Daniel

2015-01-01

The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whether MERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol-DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction with MERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response. PMID:25624460

Targeting the Intratumoral Dendritic Cells by the Oncolytic Adenoviral Vaccine Expressing RANTES Elicits Potent Antitumor Immunity

PubMed Central

Lapteva, Natalia; Aldrich, Melissa; Weksberg, David; Rollins, Lisa; Goltsova, Tatiana; Chen, Si-Yi; Huang, Xue F.

2014-01-01

Summary Dendritic cells (DCs) are professional antigen (Ag)-presenting cells capable of inducing immune responses to tumor Ags and, therefore, play a central role in the induction of antitumor immunity. There is a large amount of evidence, however, about paucity of tumor-associated DCs and that DCs’ immunogenic functions are suppressed in a tumor environment. Here we describe a potent in situ vaccine targeting tumoral DCs in vivo. This vaccine comprised of an oncolytic adenovirus expressing RANTES (regulated upon activation, normally T expressed, and presumably secreted) (Ad-RANTES-E1A), enhanced tumor infiltration, and maturation of Ag-presenting cells in vivo. In this study, we show that intratumoral vaccinations with Ad-RANTES-E1A induced significant primary tumor growth regression and blocked metastasis formation in JC and E.G-7 murine tumor models. This vaccine recruited DCs, macrophages, natural killer cells, and CD8+ T cells to the tumor site, and thus enhanced Ag-specific cytotoxic T lymphocyte responses and natural killer cell responses. DCs purified from the Ad-RANTES-E1A–treated E.G-7 tumors secreted significantly higher levels of interferon-γ and interleukin-12, as compared with control groups and more efficiently enhanced CD8+ T-cell response. This in situ immunization strategy could be a potent antitumor immunotherapy approach for aggressive established tumors. PMID:19238013

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

PubMed

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

2012-05-01

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

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

PubMed Central

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

2014-01-01

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

Immunomodulatory function of regulatory dendritic cells induced by mesenchymal stem cells.

PubMed

Zhao, Zhi-Gang; Xu, Wen; Sun, Li; You, Yong; Li, Fang; Li, Qiu-Bai; Zou, Ping

2012-01-01

Mesenchymal stem cells (MSCs) provide an excellent model for development of stem cell therapeutics, and their potential treatment in the immunopathogenic diseases have gained further interest after demonstration of immunomodulatory effects on complicated interactions between T cells and even dendritic cells (DCs). However, the mechanisms underlying these immunoregulatory effects of MSCs are poorly understood. In this study, we show that bone marrow derived MSCs can differentiate mature DCs (mDCs) into a distinct regulatory DC population. Compared with mDCs, they have lower expression of CD1a, CD80, CD86 and CD40, but higher expression of CD11b. MSCs induced DCs (MSC-DCs) can hardly stimulate T-cell proliferation even when MSC-DCs are stimulated by LPS. In addition, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-DCs are also observed. Moreover, MSC-DCs can efficiently generate CD4+CD25+Foxp3+ Treg cells from CD4+CD25-Foxp3-T cells. The inhibitory function of MSC-DCs is mediated not only through TGF-β1, but also by inducing the production of Treg cells or T-cell anergy. These results demonstrate that the immunomodulatory effects of regulatory DCs induced by MSCs provide efficacious treatment for immunopathogenic diseases.

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

PubMed

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

2016-11-15

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

Shaping memory accuracy by left prefrontal transcranial direct current stimulation.

PubMed

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

2014-03-12

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

Construction of new skin models and calculation of skin dose coefficients for electron exposures

NASA Astrophysics Data System (ADS)

Yeom, Yeon Soo; Kim, Chan Hyeong; Nguyen, Thang Tat; Choi, Chansoo; Han, Min Cheol; Jeong, Jong Hwi

2016-08-01

The voxel-type reference phantoms of the International Commission on Radiological Protection (ICRP), due to their limited voxel resolutions, cannot represent the 50- μm-thick radiosensitive target layer of the skin necessary for skin dose calculations. Alternatively, in ICRP Publication 116, the dose coefficients (DCs) for the skin were calculated approximately, averaging absorbed dose over the entire skin depth of the ICRP phantoms. This approximation is valid for highly-penetrating radiations such as photons and neutrons, but not for weakly penetrating radiations like electrons due to the high gradient in the dose distribution in the skin. To address the limitation, the present study introduces skin polygon-mesh (PM) models, which have been produced by converting the skin models of the ICRP voxel phantoms to a high-quality PM format and adding a 50- μm-thick radiosensitive target layer into the skin models. Then, the constructed skin PM models were implemented in the Geant4 Monte Carlo code to calculate the skin DCs for external exposures of electrons. The calculated values were then compared with the skin DCs of the ICRP Publication 116. The results of the present study show that for high-energy electrons (≥ 1 MeV), the ICRP-116 skin DCs are, indeed, in good agreement with the skin DCs calculated in the present study. For low-energy electrons (< 1 MeV), however, significant discrepancies were observed, and the ICRP-116 skin DCs underestimated the skin dose as much as 15 times for some energies. Besides, regardless of the small tissue weighting factor of the skin ( w T = 0.01), the discrepancies in the skin dose were found to result in significant discrepancies in the effective dose, demonstarting that the effective DCs in ICRP-116 are not reliable for external exposure to electrons.

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

PubMed

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

2016-01-04

Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations. Copyright © 2015 Elsevier Inc. All rights reserved.

Combining Carbon Ion Radiotherapy and Local Injection of {alpha}-Galactosylceramide-Pulsed Dendritic Cells Inhibits Lung Metastases in an In Vivo Murine Model

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

Ohkubo, Yu; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi; Iwakawa, Mayumi, E-mail: mayumii@nirs.go.j

2010-12-01

Purpose: Our previous report indicated that carbon ion beam irradiation upregulated membrane-associated immunogenic molecules, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of local combination therapy of carbon ion radiotherapy and immunotherapy was examined by use of an in vivo murine model. Methods and Materials: Tumors of mouse squamous cell carcinoma (NR-S1) cells inoculated in the legs of C3H/HeSlc mice were locally irradiated with a single 6-Gy dose of carbon ions (290 MeV/nucleon, 6-cm spread-out Bragg peak). Thirty-six hours after irradiation, {alpha}-galactosylceramide-pulsed dendritic cells (DCs) were injected into the leg tumor. We investigated the effects on distant lungmore » metastases by counting the numbers of lung tumor colonies, making pathologic observations, and assessing immunohistochemistry. Results: The mice with no treatment (control) presented with 168 {+-} 53.8 metastatic nodules in the lungs, whereas the mice that received the combination therapy of carbon ion irradiation and DCs presented with 2.6 {+-} 1.9 (P = 0.009) at 2 weeks after irradiation. Immunohistochemistry showed that intracellular adhesion molecule 1, which activates DCs, increased from 6 h to 36 h after irradiation in the local tumors of the carbon ion-irradiated group. The expression of S100A8 in lung tissue, a marker of the lung pre-metastatic phase, was decreased only in the group with a combination of carbon ions and DCs. Conclusions: The combination of carbon ion radiotherapy with the injection of {alpha}-galactosylceramide-pulsed DCs into the primary tumor effectively inhibited distant lung metastases.« less

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

PubMed

Brückner, Sabrina; Kammer, Thomas

2017-02-20

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

Radiation- and Age-Associated Changes in Peripheral Blood Dendritic Cell Populations among Aging Atomic Bomb Survivors in Japan.

PubMed

Kajimura, Junko; Lynch, Heather E; Geyer, Susan; French, Benjamin; Yamaoka, Mika; Shterev, Ivo D; Sempowski, Gregory D; Kyoizumi, Seishi; Yoshida, Kengo; Misumi, Munechika; Ohishi, Waka; Hayashi, Tomonori; Nakachi, Kei; Kusunoki, Yoichiro

2017-11-30

Previous immunological studies in atomic bomb survivors have suggested that radiation exposure leads to long-lasting changes, similar to immunological aging observed in T-cell-adaptive immunity. However, to our knowledge, late effects of radiation on dendritic cells (DCs), the key coordinators for activation and differentiation of T cells, have not yet been investigated in humans. In the current study, we hypothesized that numerical and functional decreases would be observed in relationship to radiation dose in circulating conventional DCs (cDCs) and plasmacytoid DCs (pDCs) among 229 Japanese A-bomb survivors. Overall, the evidence did not support this hypothesis, with no overall changes in DCs or functional changes observed with radiation dose. Multivariable regression analysis for radiation dose, age and gender effects revealed that total DC counts as well as subpopulation counts decreased in relationship to increasing age. Further analyses revealed that in women, absolute numbers of pDCs showed significant decreases with radiation dose. A hierarchical clustering analysis of gene expression profiles in DCs after Toll-like receptor stimulation in vitro identified two clusters of participants that differed in age-associated expression levels of genes involved in antigen presentation and cytokine/chemokine production in cDCs. These results suggest that DC counts decrease and expression levels of gene clusters change with age. More than 60 years after radiation exposure, we also observed changes in pDC counts associated with radiation, but only among women.

Radiation- and Age-Associated Changes in Peripheral Blood Dendritic Cell Populations among Aging Atomic Bomb Survivors in Japan.

PubMed

Kajimura, Junko; Lynch, Heather E; Geyer, Susan; French, Benjamin; Yamaoka, Mika; Shterev, Ivo D; Sempowski, Gregory D; Kyoizumi, Seishi; Yoshida, Kengo; Misumi, Munechika; Ohishi, Waka; Hayashi, Tomonori; Nakachi, Kei; Kusunoki, Yoichiro

2018-01-01

Previous immunological studies in atomic bomb survivors have suggested that radiation exposure leads to long-lasting changes, similar to immunological aging observed in T-cell-adaptive immunity. However, to our knowledge, late effects of radiation on dendritic cells (DCs), the key coordinators for activation and differentiation of T cells, have not yet been investigated in humans. In the current study, we hypothesized that numerical and functional decreases would be observed in relationship to radiation dose in circulating conventional DCs (cDCs) and plasmacytoid DCs (pDCs) among 229 Japanese A-bomb survivors. Overall, the evidence did not support this hypothesis, with no overall changes in DCs or functional changes observed with radiation dose. Multivariable regression analysis for radiation dose, age and gender effects revealed that total DC counts as well as subpopulation counts decreased in relationship to increasing age. Further analyses revealed that in women, absolute numbers of pDCs showed significant decreases with radiation dose. A hierarchical clustering analysis of gene expression profiles in DCs after Toll-like receptor stimulation in vitro identified two clusters of participants that differed in age-associated expression levels of genes involved in antigen presentation and cytokine/chemokine production in cDCs. These results suggest that DC counts decrease and expression levels of gene clusters change with age. More than 60 years after radiation exposure, we also observed changes in pDC counts associated with radiation, but only among women.

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

NASA Astrophysics Data System (ADS)

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.

Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers.

PubMed

Martin-Gayo, Enrique; Buzon, Maria Jose; Ouyang, Zhengyu; Hickman, Taylor; Cronin, Jacqueline; Pimenova, Dina; Walker, Bruce D; Lichterfeld, Mathias; Yu, Xu G

2015-06-01

The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.

Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii.

PubMed

John, Beena; Harris, Tajie H; Tait, Elia D; Wilson, Emma H; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A

2009-07-01

To better understand the initiation of CD8(+) T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8(+) T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8(+) T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8(+) T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8(+) T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis.

Dynamic Imaging of CD8+ T Cells and Dendritic Cells during Infection with Toxoplasma gondii

PubMed Central

John, Beena; Harris, Tajie H.; Tait, Elia D.; Wilson, Emma H.; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S.; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A.

2009-01-01

To better understand the initiation of CD8+ T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8+ T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8+ T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8+ T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8+ T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis. PMID:19578440

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

PubMed

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.

Immune phenotype in children with therapy-naïve remitted and relapsed Crohn’s disease

PubMed Central

Cseh, Aron; Vasarhelyi, Barna; Molnar, Kriszta; Szalay, Balazs; Svec, Peter; Treszl, Andras; Dezsofi, Antal; Lakatos, Peter Laszlo; Arato, Andras; Tulassay, Tivadar; Veres, Gabor

2010-01-01

AIM: To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy-naïve childhood Crohn’s disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease. METHODS: We enrolled 26 pediatric patients with CD. 14 therapy-naïve CD children; of those, 10 children remitted on conventional therapy and formed the remission group. We also tested another group of 12 children who relapsed with conventional therapy and were given infliximab; and 15 healthy children who served as controls. The prevalence of Th1 and Th2, naïve and memory, activated and regulatory T cells, along with the members of innate immunity such as natural killer (NK), NK-T, myeloid and plasmocytoid dendritic cells (DCs), monocytes and Toll-like receptor (TLR)-2 and TLR-4 expression were determined in peripheral blood samples. RESULTS: Children with therapy-naïve CD and those in relapse showed a decrease in Th1 cell prevalence. Simultaneously, an increased prevalence of memory and activated lymphocytes along with that of DCs and monocytes was observed. In addition, the ratio of myeloid /plasmocytoid DCs and the prevalence of TLR-2 or TLR-4 positive DCs and monocytes were also higher in therapy-naïve CD than in controls. The majority of alterations diminished in remitted CD irrespective of whether remission was obtained by conventional or biological therapy. CONCLUSION: The finding that immune phenotype is normalized in remission suggests a link between immune phenotype and disease activity in childhood CD. Our observations support the involvement of members of the adaptive and innate immune systems in childhood CD. PMID:21157977

Organizational consequences of staff turnover in outpatient substance abuse treatment programs.

PubMed

Knight, Danica K; Becan, Jennifer E; Flynn, Patrick M

2012-03-01

The purpose of this study was to examine the impact of staff turnover on perceptions of organizational demands and support among staff who remained employed in substance abuse treatment programs. The sample consisted of 353 clinical staff from 63 outpatient agencies. Two scales from the Survey of Organizational Functioning measured work environment demands (stress and inadequate staffing), and 3 measured supportive work relationships (communication, cohesion, and peer collaboration). Results from a series of multilevel models documented that counselors working in programs that had previously experienced high staff turnover perceived higher demands and lower support within their organization, even after controlling for other potentially burdensome factors such as budget, census, and individual measures of workload. Two individual-level variables, caseload and tenure, were important determinants of work environment demands but were not related to supportive work relationships. Findings suggest that staff turnover increases workplace demands, decreases perceptions of support, and underscores the need to reduce stress and minimize subsequent turnover among clinical staff. Copyright © 2012 Elsevier Inc. All rights reserved.

Organizational Consequences of Staff Turnover in Outpatient Substance Abuse Treatment Programs

PubMed Central

Knight, Danica K.; Edwards, Jennifer R.; Flynn, Patrick M.

2014-01-01

The purpose of this study was to examine the impact of staff turnover on perceptions of organizational demands and support among staff who remained employed in substance abuse treatment programs. The sample consisted of 353 clinical staff from 63 outpatient agencies. Two scales from the Survey of Organizational Functioning (SOF) measured work-environment demands (Stress, Inadequate Staffing), and three measured supportive work relationships (Communication, Cohesion, Peer Collaboration). Results from a series of multilevel models documented that counselors working in programs that had previously experienced high staff turnover perceived higher demands and lower support within their organization, even after controlling for other potentially burdensome factors such as budget, census, and individual measures of workload. Two individual-level variables, caseload and tenure, were important determinants of work-environment demands, but were not related to supportive work relationships. Findings suggest that staff turnover increases workplace demands and decreases perceptions of support, and underscore the need to reduce stress and minimize subsequent turnover among clinical staff. PMID:22154028

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

PubMed Central

Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory intracortical interneuron-networks, cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and validation need to be dedicated to this question to confirm this relationship. PMID:25612896

Quality controls in cellular immunotherapies: rapid assessment of clinical grade dendritic cells by gene expression profiling.

PubMed

Castiello, Luciano; Sabatino, Marianna; Zhao, Yingdong; Tumaini, Barbara; Ren, Jiaqiang; Ping, Jin; Wang, Ena; Wood, Lauren V; Marincola, Francesco M; Puri, Raj K; Stroncek, David F

2013-02-01

Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers.

Xenon Blocks Neuronal Injury Associated with Decompression

PubMed Central

Blatteau, Jean-Eric; David, Hélène N.; Vallée, Nicolas; Meckler, Cedric; Demaistre, Sebastien; Lambrechts, Kate; Risso, Jean-Jacques; Abraini, Jacques H.

2015-01-01

Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS. PMID:26469983

Xenon Blocks Neuronal Injury Associated with Decompression.

PubMed

Blatteau, Jean-Eric; David, Hélène N; Vallée, Nicolas; Meckler, Cedric; Demaistre, Sebastien; Lambrechts, Kate; Risso, Jean-Jacques; Abraini, Jacques H

2015-10-15

Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS.

Defining Nitrogen Kinetics for Air Break in Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, Johnny

2009-01-01

Actual tissue nitrogen (N2) kinetics are complex; the uptake and elimination is often approximated with a single half-time compartment in statistical descriptions of denitrogenation [prebreathe (PB)] protocols. Air breaks during PB complicate N2 kinetics. A comparison of symmetrical versus asymmetrical N2 kinetics was performed using the time to onset of hypobaric decompression sickness (DCS) as a surrogate for actual venous N2 tension. Published results of 12 tests involving 179 hypobaric exposures in altitude chambers after PB, with and without air breaks, provide the complex protocols from which to model N2 kinetics. DCS survival time for combined control and air breaks were described with an accelerated log logistic model where N2 uptake and elimination before, during, and after the air break was computed with a simple exponential function or a function that changed half-time depending on ambient N2 partial pressure. P1N2-P2 = delta P defined DCS dose for each altitude exposure, where P2 was the test altitude and P1N2 was computed N2 pressure at the beginning of the altitude exposure. The log likelihood (LL) without DCS dose (null model) was -155.6, and improved (best-fit) to -97.2 when dose was defined with a 240 min half-time for both N2 elimination and uptake during the PB. The description of DCS survival time was less precise with asymmetrical N2 kinetics, for example, LL was -98.9 with 240 min half-time elimination and 120 min half-time uptake. The statistical regression described survival time mechanistically linked to symmetrical N2 kinetics during PBs that also included air breaks. The results are data-specific, and additional data may change the conclusion. The regression is useful to compute additional PB time to compensate for an air break in PB within the narrow range of tested conditions.

Decompression sickness after air break in prebreathe described with a survival model.

PubMed

Conkin, Johnny

2011-06-01

A perception exists in aerospace that a brief interruption in a 100% oxygen prebreathe (PB) by breathing air has a substantial decompression sickness (DCS) consequence. The consequences of an air break during PB on the subsequent hypobaric DCS outcomes were evaluated. The hypothesis was that asymmetrical and not symmetrical nitrogen (N2) kinetics was best to model the distribution of subsequent DCS survival times after PBs that included air breaks. DCS survival times from 95 controls for a 60-min PB prior to 2- or 4-h exposures to 4.37 psia (9144 m; 30,000 ft) were analyzed along with 3 experimental conditions: 10-min air break (N = 40), 20-min air break (N = 40), or 60-min air break (N = 32) 30 min into the PB followed by 30 min of PB. Ascent rate was 1524 m x min(-1) and all 207 exposures included light exercise at 4.37 psia. Various computations of decompression dose were evaluated; either the difference or ratio of P1N2 and P2, where P1N2 was computed tissue N2 pressure to account for the PB and P2 was altitude pressure. Survival times were described with an accelerated log logistic model with asymmetrical N2 kinetics defining P1N2--P2 as best decompression dose. Exponential N2 uptake during the air break was described with a 10-min half time and N2 elimination during PB with a 60-min half time. A simple conclusion about compensation for air break is not possible because the duration and location of a break in a PB is variable. The resulting survival model is used to compute additional PB time to compensate for an air break in PB within the range of tested conditions.

EEG Driven tDCS Versus Bifrontal tDCS for Tinnitus

PubMed Central

De Ridder, Dirk; Vanneste, Sven

2012-01-01

Tinnitus is the perception of a sound in the absence of any objective physical sound source. Transcranial Direct Current Stimulation (tDCS) induces shifts in membrane resting potentials depending on the polarity of the stimulation: under the anode gamma band activity increases, whereas under the cathode the opposite occurs. Both single and multiple sessions of tDCS over the dorsolateral prefrontal cortex (DLPFC; anode over right DLPFC) yield a transient improvement in tinnitus intensity and tinnitus distress. The question arises whether optimization of the tDCS protocol can be obtained by using EEG driven decisions on where to place anode and cathode. Using gamma band functional connectivity could be superior to gamma band activity as functional connectivity determines the tinnitus network in many aspects of chronic tinnitus. Six-hundred-seventy-five patients were included in the study: 265 patients received tDCS with cathodal electrode placed over the left DLPFC and the anode placed overlying the right DLPFC, 380 patients received tDCS based on EEG connectivity, and 65 received no tDCS (i.e., waiting list control group). Repeated measures ANOVA revealed a significant main effect for pre versus post measurement. Bifrontal tDCS in comparison to EEG driven tDCS had a larger reduction for both tinnitus distress and tinnitus intensity. Whereas the results of the bifrontal tDCS seem to confirm previous studies, the use of gamma band functional connectivity seems not to bring any advantage to tDCS for tinnitus suppression. Using other potential biomarkers, such as gamma band activity, or theta functional connectivity could theoretically be of use. Further studies will have to elucidate whether brain state based tDCS has any advantages over “blind” bifrontal stimulation. PMID:23055986

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

PubMed

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

2014-01-01

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

Dendritic Cell Immune Responses in HIV-1 Controllers.

PubMed

Martin-Gayo, Enrique; Yu, Xu G

2017-02-01

Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.

Technical advance: live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung.

PubMed

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-09-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. © 2014 Society for Leukocyte Biology.

Impact of job characteristics on psychological health of Chinese single working women.

PubMed

Yeung, D Y; Tang, C S

2001-01-01

This study aims at investigating the impact of individual and contextual job characteristics of control, psychological and physical demand, and security on psychological distress of 193 Chinese single working women in Hong Kong. The mediating role of job satisfaction in the job characteristics-distress relation is also assessed. Multiple regression analysis results show that job satisfaction mediates the effects of job control and security in predicting psychological distress; whereas psychological job demand has an independent effect on mental distress after considering the effect of job satisfaction. This main effect model indicates that psychological distress is best predicted by small company size, high psychological job demand, and low job satisfaction. Results from a separate regression analysis fails to support the overall combined effect of job demand-control on psychological distress. However, a significant physical job demand-control interaction effect on mental distress is noted, which reduces slightly after controlling the effect of job satisfaction.

Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.

PubMed

Chhatbar, Pratik Y; Kautz, Steven A; Takacs, Istvan; Rowland, Nathan C; Revuelta, Gonzalo J; George, Mark S; Bikson, Marom; Feng, Wuwei

2018-03-13

Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of experience-based perceptual learning in the face inversion effect.

PubMed

Civile, Ciro; Obhi, Sukhvinder S; McLaren, I P L

2018-04-03

Perceptual learning of the type we consider here is a consequence of experience with a class of stimuli. It amounts to an enhanced ability to discriminate between stimuli. We argue that it contributes to the ability to distinguish between faces and recognize individuals, and in particular contributes to the face inversion effect (better recognition performance for upright vs inverted faces). Previously, we have shown that experience with a prototype defined category of checkerboards leads to perceptual learning, that this produces an inversion effect, and that this effect can be disrupted by Anodal tDCS to Fp3 during pre-exposure. If we can demonstrate that the same tDCS manipulation also disrupts the inversion effect for faces, then this will strengthen the claim that perceptual learning contributes to that effect. The important question, then, is whether this tDCS procedure would significantly reduce the inversion effect for faces; stimuli that we have lifelong expertise with and for which perceptual learning has already occurred. Consequently, in the experiment reported here we investigated the effects of anodal tDCS at Fp3 during an old/new recognition task for upright and inverted faces. Our results show that stimulation significantly reduced the face inversion effect compared to controls. The effect was one of reducing recognition performance for upright faces. This result is the first to show that tDCS affects perceptual learning that has already occurred, disrupting individuals' ability to recognize upright faces. It provides further support for our account of perceptual learning and its role as a key factor in face recognition. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transcranial direct current stimulation enhances verbal working memory training performance over time and near transfer outcomes.

PubMed

Richmond, Lauren L; Wolk, David; Chein, Jason; Olson, Ingrid R

2014-11-01

Studies attempting to increase working memory (WM) capacity show promise in enhancing related cognitive functions but have also raised criticism in the broader scientific community given the inconsistent findings produced by these studies. Transcranial direct current stimulation (tDCS) has been shown to enhance WM performance in a single session [Fregni, F., Boggio, P., Nitsche, M., Bermpohl, F., Anatal, A., Feredoes, E., et al. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Experimental Brain Research, 166, 23-30, 2005]; however, the extent to which tDCS might enhance learning on a WM training regime and the extent to which learning gains might transfer outside the training task remains largely unknown. To this end, participants engaged in an adaptive WM training task [previously utilized in Richmond, L., Morrison, A., Chein, J., & Olson, I. Working memory training and transfer in older adults. Psychology & Aging, 26, 813-822, 2011; Chein, J., & Morrison, A. Expanding the mind's workspace: Training and transfer effects with a complex working memory span task. Psychonomic Bulletin & Review, 17, 193-199, 2010] for 10 sessions over 2 weeks, concurrent with either active or sham stimulation of dorsolateral pFC. Before and after training, a battery of tests tapping domains known to relate to WM abilities was administered. Results show that tDCS enhanced learning on the verbal portion of the training task by 3.65 items. Furthermore, tDCS was shown to enhance near transfer to other untrained WM tasks in comparison with a no-contact control group. These results lend support to the idea that tDCS might bolster training and transfer gains in populations with compromised WM abilities.

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

PubMed Central

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

2017-01-01

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

Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial

PubMed Central

Chang, Wei-Ju; Bennell, Kim L.; Hodges, Paul W.; Hinman, Rana S.; Young, Carolyn L.; Buscemi, Valentina; Liston, Matthew B.

2017-01-01

A randomised, assessor- and participant-blind, sham-controlled trial was conducted to assess the safety and feasibility of adding transcranial direct current stimulation (tDCS) to quadriceps strengthening exercise in knee osteoarthritis (OA), and provide data to inform a fully powered trial. Participants were randomised to receive active tDCS+exercise (AT+EX) or sham tDCS+exercise (ST+EX) twice weekly for 8 weeks whilst completing home exercises twice per week. Feasibility, safety, patient-perceived response, pain, function, pressure pain thresholds (PPTs) and conditioned pain modulation (CPM) were assessed before and after treatment. Fifty-seven people were screened for eligibility. Thirty (52%) entered randomisation and 25 (84%) completed the trial. One episode of headache in the AT+EX group was reported. Pain reduced in both groups following treatment (AT+EX: p<0.001, partial η2 = 0.55; ST+EX: p = 0.026, partial η2 = 0.18) but no between-group differences were observed (p = 0.18, partial η2 = 0.08). Function improved in the AT+EX (p = 0.01, partial η2 = 0.22), but not the ST+EX (p = 0.16, partial η2 = 0.08) group, between-group differences did not reach significance (p = 0.28, partial η2 = 0.052). AT+EX produced greater improvements in PPTs than ST+EX (p<0.05) (superolateral knee: partial η2 = 0.17; superior knee: partial η2 = 0.3; superomedial knee: partial η2 = 0.26). CPM only improved in the AT+EX group but no between-group difference was observed (p = 0.054, partial η2 = 0.158). This study provides the first feasibility and safety data for the addition of tDCS to quadriceps strengthening exercise in knee OA. Our data suggest AT+EX may improve pain, function and pain mechanisms beyond that of ST+EX, and provides support for progression to a fully powered randomised controlled trial. PMID:28665989

Venous gas embolism after an open-water air dive and identical repetitive dive.

PubMed

Schellart, N A M; Sterk, W

2012-01-01

Decompression tables indicate that a repetitive dive to the same depth as a first dive should be shortened to obtain the same probability of occurrence of decompression sickness (pDCS). Repetition protocols are based on small numbers, a reason for re-examination. Since venous gas embolism (VGE) and pDCS are related, one would expect a higher bubble grade (BG) of VGE after the repetitive dive without reducing bottom time. BGs were determined in 28 divers after a first and an identical repetitive air dive of 40 minutes to 20 meters of sea water. Doppler BG scores were transformed to log number of bubbles/cm2 (logB) to allow numerical analysis. With a previously published model (Model2), pDCS was calculated for the first dive and for both dives together. From pDCS, theoretical logBs were estimated with a pDCS-to-logB model constructed from literature data. However, pDCS the second dive was provided using conditional probability. This was achieved in Model2 and indirectly via tissue saturations. The combination of both models shows a significant increase of logB after the second dive, whereas the measurements showed an unexpected lower logB. These differences between measurements and model expectations are significant (p-values < 0.01). A reason for this discrepancy is uncertain. The most likely speculation would be that the divers, who were relatively old, did not perform physical activity for some days before the first dive. Our data suggest that, wisely, the first dive after a period of no exercise should be performed conservatively, particularly for older divers.

tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study.

PubMed

Kim, Soyoung; Stephenson, Mary C; Morris, Peter G; Jackson, Stephen R

2014-10-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task. Copyright © 2014. Published by Elsevier Inc.

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

PubMed

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

2018-05-28

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

Demonstration of application-driven network slicing and orchestration in optical/packet domains: on-demand vDC expansion for Hadoop MapReduce optimization.

PubMed

Kong, Bingxin; Liu, Siqi; Yin, Jie; Li, Shengru; Zhu, Zuqing

2018-05-28

Nowadays, it is common for service providers (SPs) to leverage hybrid clouds to improve the quality-of-service (QoS) of their Big Data applications. However, for achieving guaranteed latency and/or bandwidth in its hybrid cloud, an SP might desire to have a virtual datacenter (vDC) network, in which it can manage and manipulate the network connections freely. To address this requirement, we design and implement a network slicing and orchestration (NSO) system that can create and expand vDCs across optical/packet domains on-demand. Considering Hadoop MapReduce (M/R) as the use-case, we describe the proposed architectures of the system's data, control and management planes, and present the operation procedures for creating, expanding, monitoring and managing a vDC for M/R optimization. The proposed NSO system is then realized in a small-scale network testbed that includes four optical/packet domains, and we conduct experiments in it to demonstrate the whole operations of the data, control and management planes. Our experimental results verify that application-driven on-demand vDC expansion across optical/packet domains can be achieved for M/R optimization, and after being provisioned with a vDC, the SP using the NSO system can fully control the vDC network and further optimize the M/R jobs in it with network orchestration.

Detoxification of corn stover and corn starch pyrolysis liquors by Pseudomonas putida and Streptomyces setonii suspended cells and plastic compost support biofilms.

PubMed

Khiyami, Mohammad A; Pometto Iii, Anthony L; Brown, Robert C

2005-04-20

Plant biomass can be liquefied into fermentable sugars (levoglucosan then to glucose) for the production of ethanol, lactic acid, enzymes, and more by a process called pyrolysis. During the process microbial inhibitors are also generated. Pseudomonas putida (ATCC 17484) and Streptomyces setonii75Vi2 (ATCC 39116) were employed to degrade microbial inhibitors in diluted corn stover (Dcs) and diluted corn starch (Dst) pyrolysis liquors. The detoxification process evaluation included measuring total phenols and changes in UV spectra, a GC-MS analysis, and a bioassay, which employed Lactobacillus casei subsp. rhamosus (ATCC 11443) growth as an indicator of detoxification. Suspended-cell cultures illustrated limited detoxification ability of Dcs and Dst. P. putida and S. setoniiplastic compost support (PCS) biofilm continuous-stirred-tank-reactor pure cultures detoxified 10 and 25% (v/v) Dcs and Dst, whereas PCS biofilm mixed culture also partially detoxified 50% (v/v) Dcs and Dst in repeated batch culture. Therefore, PCS biofilm mixed culture is the process of choice to detoxify diluted pyrolysis liquors.

Fatigue in employees with diabetes: its relation with work characteristics and diabetes related burden

PubMed Central

Weijman, I; Ros, W; Rutten, G; Schaufeli, W; Schabracq, M; Winnubst, J

2003-01-01

Aims: To examine the relations between work characteristics as defined by the Job Demand-Control-Support model (JDCS) (that is, job demands, decision latitude, and social support), diabetes related burden (symptoms, seriousness of disease, self care activities, and disease duration), and fatigue in employees with diabetes mellitus. Methods: Employees (n = 292) aged 30–60 years, with insulin treated diabetes, filled in self administered questionnaires that assess the above mentioned components of the JDCS model and diabetes related burdens. Results: Both work and diabetes related factors are related to fatigue in employees with diabetes. Regression analyses revealed that work characteristics explain 19.1% of the variance in fatigue; lack of support, and the interaction of job demands and job control contribute significantly. Diabetes related factors explain another 29.0% of the variance, with the focus on diabetes related symptoms and the burden of adjusting insulin dosage to circumstances. Fatigue is more severe in case of lack of social support at work, high job demands in combination with a lack of decision latitude, more burden of adjusting insulin dosage to circumstances, and more diabetic symptoms. Furthermore, regression analysis revealed that diabetic symptoms and the burden of adjusting the insulin dosage to circumstances are especially relevant in combination with high job demands. Conclusions: Both diabetes and work should be taken into consideration—by (occupational) physicians as well as supervisors—in the communication with people with diabetes. PMID:12782754

Role and contribution of pulmonary CD103+ dendritic cells in the adaptive immune response to Mycobacterium tuberculosis.

PubMed

Koh, Vanessa Hui Qi; Ng, See Liang; Ang, Michelle Lay Teng; Lin, Wenwei; Ruedl, Christiane; Alonso, Sylvie

2017-01-01

Despite international control programmes, the global burden of tuberculosis remains enormous. Efforts to discover novel drugs have largely focused on targeting the bacterium directly. Alternatively, manipulating the host immune response may represent a valuable approach to enhance immunological clearance of the bacilli, but necessitates a deeper understanding of the immune mechanisms associated with protection against Mycobacterium tuberculosis infection. Here, we examined the various dendritic cells (DC) subsets present in the lung and draining lymph nodes (LN) from mice intra-tracheally infected with M. tuberculosis. We showed that although limited in number, pulmonary CD103 + DCs appeared to be involved in the initial transport of mycobacteria to the draining mediastinal LN and subsequent activation of T cells. Using CLEC9A-DTR transgenic mice enabling the inducible depletion of CD103 + DCs, we established that this DC subset contributes to the control of mycobacterial burden and plays a role in the early activation of T cells, in particular CD8 + T cells. Our findings thus support a previously unidentified role for pulmonary CD103 + DCs in the rapid mobilization of mycobacteria from the lungs to the draining LN soon after exposure to M. tuberculosis, which is a critical step for the development of the host adaptive immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

The dorsolateral prefrontal cortex (DLPFC) plays an important role in the regulation of food intake. Several previous studies demonstrated that a single session of transcranial direct current stimulation (tDCS) of the DLPFC reduces food craving and caloric intake. We hypothesized that repeated tDCS of the right DLPFC cortex may exert long-term changes in food craving in young, healthy adults and that these changes may differ between normal and overweight subjects. Thirty healthy individuals who reported frequent food cravings without a prior history of eating disorders were initially recruited. Subjects were randomized into an ACTIVE group who received 5 days of real tDCS (20 minutes, anode right-cathode left montage, 2 mA with current density kept at 0.06 mA/cm2, 1 min ramp-up/ramp-down), and a SHAM group, who received one day of real tDCS, on the first day (same parameters), followed by 4 days of sham tDCS. Food craving intensity was examined by Food Craving Questionnaires State and Trait and Food Craving Inventory before, during, (5-days) and one month (30-days) after tDCS. Single session of tDCS significantly reduced the intensity of current food craving (FCQ-S). Five days of active tDCS significantly reduced habitual experiences of food craving (FCQ-T), when compared to baseline pre-stimulation levels. Furthermore, both current (FCQ-S) and habitual craving (FCQ-T) were significantly reduced 30 days after active tDCS, while sham tDCS, i.e. a single tDCS session did not have significant effects. Also, active tDCS significantly decreased craving for fast food and sweets, and to a lesser degree for fat, while it did not have significant effects on craving for carbohydrates (FCI). There were no significant differences between individual FCQ-T subscales (craving dimensions) after 5 or 30 days of either sham or active tDCS. Changes in craving were not significantly associated with the initial weight, or with weight changes 30 days after the stimulation in the subjects. The results confirm earlier findings that single session of tDCS has immediate effects in reducing food craving. They also show that repeated tDCS over the right DLPFC may increase the duration of its effects, which may be present 30 days after the stimulation. These results support further investigation of the use of tDCS in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-03-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-12-01

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

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

PubMed

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

2015-10-01

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

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

PubMed

Pulendran, Bali

2015-01-01

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

Some Results of Weak Anticipative Concept Applied in Simulation Based Decision Support in Enterprise

NASA Astrophysics Data System (ADS)

Kljajić, Miroljub; Kofjač, Davorin; Kljajić Borštnar, Mirjana; Škraba, Andrej

2010-11-01

The simulation models are used as for decision support and learning in enterprises and in schools. Tree cases of successful applications demonstrate usefulness of weak anticipative information. Job shop scheduling production with makespan criterion presents a real case customized flexible furniture production optimization. The genetic algorithm for job shop scheduling optimization is presented. Simulation based inventory control for products with stochastic lead time and demand describes inventory optimization for products with stochastic lead time and demand. Dynamic programming and fuzzy control algorithms reduce the total cost without producing stock-outs in most cases. Values of decision making information based on simulation were discussed too. All two cases will be discussed from optimization, modeling and learning point of view.

Modeling trans-spinal direct current stimulation for the modulation of the lumbar spinal motor pathways

NASA Astrophysics Data System (ADS)

Kuck, A.; Stegeman, D. F.; van Asseldonk, E. H. F.

2017-10-01

Objective. Trans-spinal direct current stimulation (tsDCS) is a potential new technique for the treatment of spinal cord injury (SCI). TsDCS aims to facilitate plastic changes in the neural pathways of the spinal cord with a positive effect on SCI recovery. To establish tsDCS as a possible treatment option for SCI, it is essential to gain a better understanding of its cause and effects. We seek to understand the acute effect of tsDCS, including the generated electric field (EF) and its polarization effect on the spinal circuits, to determine a cellular target. We further ask how these findings can be interpreted to explain published experimental results. Approach. We use a realistic full body finite element volume conductor model to calculate the EF of a 2.5 mA direct current for three different electrode configurations. We apply the calculated electric field to realistic motoneuron models to investigate static changes in membrane resting potential. The results are combined with existing knowledge about the theoretical effect on a neuronal level and implemented into an existing lumbar spinal network model to simulate the resulting changes on a network level. Main results. Across electrode configurations, the maximum EF inside the spinal cord ranged from 0.47 V m-1 to 0.82 V m-1. Axon terminal polarization was identified to be the dominant cellular target. Also, differences in electrode placement have a large influence on axon terminal polarization. Comparison between the simulated acute effects and the electrophysiological long-term changes observed in human tsDCS studies suggest an inverse relationship between the two. Significance. We provide methods and knowledge for better understanding the effects of tsDCS and serve as a basis for a more targeted and optimized application of tsDCS.

Enhancing motor performance improvement by personalizing non-invasive cortical stimulation with concurrent functional near-infrared spectroscopy and multi-modal motor measurements

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann; Alexandrakis, George

2015-03-01

Transcranial direct current stimulation (tDCS) is a non-invasive cortical stimulation technique that can facilitate task specific plasticity that can improve motor performance. Current tDCS interventions uniformly apply a chosen electrode montage to a subject population without personalizing electrode placement for optimal motor gains. We propose a novel perturbation tDCS (ptDCS) paradigm for determining a personalized electrode montage in which tDCS intervention yields maximal motor performance improvements during stimulation. PtDCS was applied to ten healthy adults and five stroke patients with upper hemiparesis as they performed an isometric wrist flexion task with their non-dominant arm. Simultaneous recordings of torque applied to a stationary handle, muscle activity by electromyography (EMG), and cortical activity by functional near-infrared spectroscopy (fNIRS) during ptDCS helped interpret how cortical activity perturbations by any given electrode montage related to changes in muscle activity and task performance quantified by a Reaction Time (RT) X Error product. PtDCS enabled quantifying the effect on task performance of 20 different electrode pair montages placed over the sensorimotor cortex. Interestingly, the electrode montage maximizing performance in all healthy adults did not match any of the ones being explored in current literature as a means of improving the motor performance of stroke patients. Furthermore, the optimal montage was found to be different in each stroke patient and the resulting motor gains were very significant during stimulation. This study supports the notion that task-specific ptDCS optimization can lend itself to personalizing the rehabilitation of patients with brain injury.

Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

NASA Astrophysics Data System (ADS)

Shin, Da Wi; Khadka, Niranjan; Fan, Jie; Bikson, Marom; Fu, Bingmei M.

2016-03-01

Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.

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

PubMed

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

2002-01-01

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

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

PubMed

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

2018-01-10

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

Methodological and conceptual issues regarding occupational psychosocial coronary heart disease epidemiology.

PubMed

Burr, Hermann; Formazin, Maren; Pohrt, Anne

2016-05-01

Overview Psychosocial occupational epidemiology has mainly focused on the demand-control and, to a much lesser extent, the effort-reward-imbalance (ERI) models. These models and the strong focus on them raise some conceptual and methodological issues we will address in the following letter. The conceptual issues include the empirical confirmation of the assumptions of these models, the extent to which the focus on the demand-control and ERI models is warranted, and whether the sub-dimensions of the scales in these models have common health effects. We argue that there is a lack of empirical approval of (i) the assumptions behind both models and (ii) the focus on these models. The methodological issues include how exposure to job strain is categorized, how ERI previously has been measured, and the validity of self-reports of job strain. We argue that (i) a population independent definition of job strain is lacking, (ii) the older measurements of ERI mix exposure and effect, and (iii) we know little regarding the validity of the measurement of the psychosocial working environment. Finally, we suggest that analyses of monitoring data with a broader focus on the psychosocial working environment can be used to shed light to some of the issues raised above. Introduction In the last three decades (1, 2), psychosocial occupational epidemiology related to coronary heart disease (CHD) has mainly focused on the job-strain model, also referred to as the demand-control model (3, 4). In this model, two aspects of work are deemed relevant: demands and control. Negative consequences to health are to be expected when high demands are simultaneously present with low control. This combination has been termed job strain (3, 4). Recently, there has also been increased interest in the ERI model (5, 6) which considers the level of effort relative to rewards at work: an imbalance is present when the efforts outweigh the rewards (5, 6). In longitudinal studies of CHD, there has been only a limited focus on investigating occupational psychosocial factors outside of these two models (1, 2). In this letter, we would like to raise some conceptual and methodological issues which are inherent to these two stress models but also which arise from the heavy emphasis placed on them. Conceptual issues The conceptual issues we discuss below are empirical confirmation of the assumptions of these models and to what extent the focus on the demand-control and ERI models is warranted. Investigating the assumptions of the models Both the demand-control and the ERI models are based on assumptions which have only been tested empirically to a limited extent (1, 2). We pose three specific questions: (i) Does the interaction of demands and control constitute a risk factor for CHD? (ii) Does the imbalance between effort and reward explain more variance in CHD risk than high effort and low reward alone? (iii) Do the sub-dimensions of the scales in these models have common health effects? Regarding the interaction of demands and control. The concept of the demand-control model is useful when the health risk of being exposed to job strain (simultaneous high demands and low control) differs greatly from the sum of individual health risks of being exposed solely to high demands and low control. If this interaction were not present, it would be warranted to look separately at high demands and low control. This would for instance counteract overlooking those persons exposed to low control but not high demands (known as "passive work"; 3, 4). It should be emphasized that the interaction of demands and control has only been tested in very few - underpowered - cases (1, 2). Initial support for an interaction within the demand-control model can be tentatively derived from the work of the IPD-Work Consortium (7): In a reanalysis of an earlier study (8), it was shown that while neither demands nor job control alone (appendix to 8) predicted CHD, job strain did when controlling for sex, age and socioeconomic status (SES) (9). This indicates that an interaction takes place. Controlling for SES is of high relevance - otherwise, the results point in a different direction (10). However, a formal test of interaction was not performed on the IPD-Work Consortium data. Even the IPD study itself might not have sufficient statistical power to analyze a possible interaction directly: this requires many more observations than simply looking at the main effects (2). If one is interested in investigating an interaction, more incident outcomes are often required (11). Regarding effort-reward imbalance. Similarly to the combined effect of demands and control described above, focusing on the ERI model makes sense only if the imbalance of effort and reward explains the risk of CHD over and above the effect of high efforts and low rewards. To our knowledge, this has not been verified in any longitudinal study of CHD (1, 2). Regarding the effect of sub-dimensions. Finally, using the scales of the two models (demands and control or efforts and rewards) is meaningful only if the sub-dimensions of the scales all have about equal effect sizes and signs. For example, the scale psychological demands covers the sub-dimensions work pace, role conflict and work amount while control covers both influence (decision authority) and opportunities for development (skill discretion). Do these dimensions predict the risk of CHD to equal amounts within their respective scales? For now, this has not been tested elaborately to our knowledge (1, 2, 12). Consequently, it is possible that certain risk factors in the psychosocial work environment may be overlooked due to different risk factors being merged into one scale. Is the focus on the demand-control and ERI models warranted? In the past, longitudinal epidemiological research on psychosocial work characteristics and their association with the risk of CHD has mainly focused on the demand-control and - to a much lesser extent - ERI models (1). For example, in a recent review (2) covering 44 papers and including 170 analyses, 70% percent of those dealt with these models or sub-dimensions thereof. Interestingly, the demand-control model alone accounted for 66% of the analyses and ERI only 4%. A further 11% of the analyses dealt with working hours, 9% with social support, 5% with job insecurity, 3% with leadership and the remaining 3% covered conflicts, justice or predictability. Maintaining the currently high degree of focus on the DC and ERI models requires evidence that job strain and ERI are by far the most important risk factors for CHD. The review by Pejtersen et al (2) has additionally pointed out that of the 44 studies mentioned above, only two - an IPD-Work Consortium study (8) and a Swedish case-control study (13) - contained analyses with sufficient statistical power to detect an elevated CHD risk of 20%. These two sufficiently powered studies available as of April 2013 have led to the following conclusions: (i) job strain was found to be predictive of CHD in the IPD-Work Consortium study (8); and (ii) both low control and low social support predicted CHD in the Swedish study (13). Recently, a well-powered study on working hours (14) indicated that long working hours constitute a risk factor for CHD. Additionally, a recently published large study on job insecurity (15) is worth mentioning. While there was not sufficient power to detect a 20% increased risk due the relatively low prevalence of job insecurity, the study did have sufficient power to find a risk of 1.32 - which is the value actually found empirically (15). Summarizing the small number of well-powered studies available at this time indicates that both model dimensions (job strain) as well as non-model dimensions (social support and working hours) predict CHD (8, 13-15). In this context, one should bear in mind that the variety of possible dimensions that can be considered as constituting "psychosocial work environment" is large. The latter is exemplified by a recent analysis of the psychosocial content of seven European work environment monitoring questionnaires which showed that there are 34 distinct dimensions of the psychosocial work environment (16). Around half of these dimensions are not found in either the demand-control or ERI models (16). These include for instance emotional demands, demands on hiding emotions, sensorial demands, meaning of work, commitment to the workplace, organizational influence, trust, social community at work, quality of leadership, predictability, role clarity, restructuring, safety culture, work life balance, and negative acts (eg, violence, bullying). Little is currently known on the health effects of these "non-model" dimensions. Research on their possible effects might show that they are small - and that the DC and ERI dimensions are indeed the main psychosocial risk factors for CHD. However, results may also point to the importance of the non-model dimensions. To date, this remains to be investigated. Methodological issues In addition to the conceptual issues discussed above, we would like to highlight some methodological issues related to one or both of these models. The three main points address: (i) how exposure to job strain is categorized; (ii) how ERI has been measured up to now; and (iii) the validity of self-reports of job strain. Practical definition of job strain Job strain is usually operationalized as a median split of the two dimensions demands and control in the population investigated (3, 17). Hence, whether a certain worker experiences job strain or not depends on which other workers are part of the sample (18). This poses a problem when the distributions of demands and control differ between populations. Comparisons between Denmark and Spain and across Europe suggest that such differences exist (19, 20), rendering it at the least a challenge to combine populations in meta-analyses. (ABSTRACT TRUNCATED)

Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask

PubMed Central

Scheldrup, Melissa; Greenwood, Pamela M.; McKendrick, Ryan; Strohl, Jon; Bikson, Marom; Alam, Mahtab; McKinley, R. Andy; Parasuraman, Raja

2014-01-01

There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation—specifically transcranial Direct Current Stimulation (tDCS)—has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical. PMID:25249958

Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

PubMed

Scheldrup, Melissa; Greenwood, Pamela M; McKendrick, Ryan; Strohl, Jon; Bikson, Marom; Alam, Mahtab; McKinley, R Andy; Parasuraman, Raja

2014-01-01

There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation-specifically transcranial Direct Current Stimulation (tDCS)-has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2003-05-01

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

A dendritic cell-stromal axis maintains immune responses in lymph nodes

PubMed Central

Kumar, Varsha; Dasoveanu, Dragos C.; Chyou, Susan; Tzeng, Te-Chen; Rozo, Cristina; Liang, Yong; Stohl, William; Fu, Yang-Xin; Ruddle, Nancy; Lu, Theresa T.

2015-01-01

Summary Within secondary lymphoid tissues, stromal reticular cells support lymphocyte function, and targeting reticular cells is a potential strategy for controlling pathogenic lymphocytes in disease. However, the mechanisms that regulate reticular cell function are not well understood. Here we found that during an immune response in lymph nodes, dendritic cells (DCs) maintain reticular cell survival in multiple compartments. DC-derived lymphotoxin beta receptor (LTβR) ligands were critical mediators, and LTβR signaling on reticular cells mediated cell survival by modulating podoplanin (PDPN). PDPN modulated integrin-mediated cell adhesion, which maintained cell survival. This DC-stromal axis maintained lymphocyte survival and the ongoing immune response. Our findings provide insight into the functions of DCs, LTβR, and PDPN and delineate a DC-stromal axis that can potentially be targeted in autoimmune or lymphoproliferative diseases. PMID:25902483

Explaining worker strain and learning: how important are emotional job demands?

PubMed

Taris, Toon W; Schreurs, Paul J G

2009-05-01

This study examined the added value of emotional job demands in explaining worker well-being, relative to the effects of task characteristics, such as quantitative job demands, job control, and coworker support. Emotional job demands were expected to account for an additional proportion of the variance in well-being. Cross-sectional data were obtained from 11,361 female Dutch home care employees. Hierarchical stepwise regression analysis demonstrated that low control, low support and high quantitative demands were generally associated with lower well-being (as measured in terms of emotional exhaustion, dedication, professional accomplishment and learning). Moreover, high emotional demands were in three out of four cases significantly associated with adverse well-being, in these cases accounting for an additional 1-6% of the variance in the outcome variables. In three out of eight cases the main effects of emotional demands on well-being were qualified by support and control, such that high control and high support either buffered the adverse effects of high emotional demands on well-being or increased the positive effects thereof. All in all, high emotional demands are as important a risk factor for worker well-being as well-established concepts like low job control and high quantitative job demands.

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS)

PubMed Central

Dittert, Natalie; Hüttner, Sandrina; Polak, Thomas; Herrmann, Martin J.

2018-01-01

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 tested in a clinical context further investigation is needed to assess the reason for the reaction increase on CS–. If this negative side effect can be avoided, tDCS may be a tool to improve exposure-based anxiety therapies. PMID:29922133

Job Stress and Job Satisfaction: Home Care Workers in a Consumer-Directed Model of Care

PubMed Central

Delp, Linda; Wallace, Steven P; Geiger-Brown, Jeanne; Muntaner, Carles

2010-01-01

Objective To investigate determinants of job satisfaction among home care workers in a consumer-directed model. Data Sources/Setting Analysis of data collected from telephone interviews with 1,614 Los Angeles home care workers on the state payroll in 2003. Data Collection and Analysis Multivariate logistic regression analysis was used to determine the odds of job satisfaction using job stress model domains of demands, control, and support. Principal Findings Abuse from consumers, unpaid overtime hours, and caring for more than one consumer as well as work-health demands predict less satisfaction. Some physical and emotional demands of the dyadic care relationship are unexpectedly associated with greater job satisfaction. Social support and control, indicated by job security and union involvement, have a direct positive effect on job satisfaction. Conclusions Policies that enhance the relational component of care may improve workers' ability to transform the demands of their job into dignified and satisfying labor. Adequate benefits and sufficient authorized hours of care can minimize the stress of unpaid overtime work, caring for multiple consumers, job insecurity, and the financial constraints to seeking health care. Results have implications for the structure of consumer-directed models of care and efforts to retain long-term care workers. PMID:20403063

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

PubMed

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

2013-12-01

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

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

PubMed

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.

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

PubMed

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

2014-02-27

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression

PubMed Central

Podda, Maria Vittoria; Cocco, Sara; Mastrodonato, Alessia; Fusco, Salvatore; Leone, Lucia; Barbati, Saviana Antonella; Colussi, Claudia; Ripoli, Cristian; Grassi, Claudio

2016-01-01

The effects of transcranial direct current stimulation (tDCS) on brain functions and the underlying molecular mechanisms are yet largely unknown. Here we report that mice subjected to 20-min anodal tDCS exhibited one-week lasting increases in hippocampal LTP, learning and memory. These effects were associated with enhanced: i) acetylation of brain-derived neurotrophic factor (Bdnf) promoter I; ii) expression of Bdnf exons I and IX; iii) Bdnf protein levels. The hippocampi of stimulated mice also exhibited enhanced CREB phosphorylation, pCREB binding to Bdnf promoter I and recruitment of CBP on the same regulatory sequence. Inhibition of acetylation and blockade of TrkB receptors hindered tDCS effects at molecular, electrophysiological and behavioral levels. Collectively, our findings suggest that anodal tDCS increases hippocampal LTP and memory via chromatin remodeling of Bdnf regulatory sequences leading to increased expression of this gene, and support the therapeutic potential of tDCS for brain diseases associated with impaired neuroplasticity. PMID:26908001

Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells.

PubMed

Kuan, Emma L; Ivanov, Stoyan; Bridenbaugh, Eric A; Victora, Gabriel; Wang, Wei; Childs, Ed W; Platt, Andrew M; Jakubzick, Claudia V; Mason, Robert J; Gashev, Anatoliy A; Nussenzweig, Michel; Swartz, Melody A; Dustin, Michael L; Zawieja, David C; Randolph, Gwendalyn J

2015-06-01

Collecting lymphatic vessels (CLVs), surrounded by fat and endowed with contractile muscle and valves, transport lymph from tissues after it is absorbed into lymphatic capillaries. CLVs are not known to participate in immune responses. In this study, we observed that the inherent permeability of CLVs allowed broad distribution of lymph components within surrounding fat for uptake by adjacent macrophages and dendritic cells (DCs) that actively interacted with CLVs. Endocytosis of lymph-derived Ags by these cells supported recall T cell responses in the fat and also generated Ag-bearing DCs for emigration into adjacent lymph nodes (LNs). Enhanced recruitment of DCs to inflammation-reactive LNs significantly relied on adipose tissue DCs to maintain sufficient numbers of Ag-bearing DCs as the LN expanded. Thus, CLVs coordinate inflammation and immunity within adipose depots and foster the generation of an unexpected pool of APCs for Ag transport into the adjacent LN. Copyright © 2015 by The American Association of Immunologists, Inc.

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis.

PubMed

Tabarkiewicz, Jacek; Postępski, Jacek; Olesińska, Edyta; Roliński, Jacek; Tuszkiewicz-Misztal, Ewa

2011-01-01

Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA) and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs) in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients' synovial fluid. We also confirmed the presence of CD206+/CD209+ in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthritis.

Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

PubMed Central

Yeste, Ada; Nadeau, Meghan; Burns, Evan J.; Weiner, Howard L.; Quintana, Francisco J.

2012-01-01

The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3+ Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG35–55 expanded the FoxP3+ Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are potential new tools to induce functional Tregs in autoimmune disorders. PMID:22745170

The role of dendritic cells in cancer.

PubMed

Hansen, Morten; Andersen, Mads Hald

2017-04-01

Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8 + T-cells and Th1 helper CD4 + T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103 + DCs, which have been shown to be experts in cross-priming and the induction of anti-tumor immunity. We also focus on two different mediators that impair the function of tumor-associated DCs: prostaglandin E 2 and β-catenin. Both of these mediators seem to be important for the exclusion of T-cells in the tumor microenvironment and may represent key pathways to target in optimized treatment regimens against cancer.

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

PubMed

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

2018-05-01

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

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

PubMed

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

2017-11-01

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

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

PubMed

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

2016-10-01

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

What is healthy work for women and men? - A case-control study of gender- and sector-specific effects of psycho-social working conditions on long-term sickness absence.

PubMed

Lidwall, Ulrik; Marklund, Staffan

2006-01-01

The aim of the study was to investigate the relevance of the demand-control model and social support in predicting long-term sickness absence (LTSA). Identifying gender- and sector- (private vs. public) specific patterns was in focus. The study uses a cross-sectional design with a case and a control group. The cases are a sample of 2 327 long-term sick listed (>60 days) and the controls are a Swedish population-based sample of 2 063. Data on sickness absence were retrieved from the Swedish national social insurance registers. Data on health, working and living conditions were gathered through a self-administered questionnaire. The results show that employed women have a notably higher risk for LTSA than employed men. High-strain jobs increase the odds for LTSA among both women and men. Active jobs were also associated with LTSA among women. The study confirms the demand-control model (job strain hypothesis) and social support and their associations with LTSA. However, the job strain hypothesis is more evident in the private sector. Active jobs with high psychological demands and high decision latitude seem to be problematic for many women, especially in the private sector. Thus, the active learning hypothesis receives no support for women in the Swedish working population in general.

Mission Control Center (MCC) System Specification for the Shuttle Orbital Flight Test (OFT) Timeframe

NASA Technical Reports Server (NTRS)

1976-01-01

System specifications to be used by the mission control center (MCC) for the shuttle orbital flight test (OFT) time frame were described. The three support systems discussed are the communication interface system (CIS), the data computation complex (DCC), and the display and control system (DCS), all of which may interfere with, and share processing facilities with other applications processing supporting current MCC programs. The MCC shall provide centralized control of the space shuttle OFT from launch through orbital flight, entry, and landing until the Orbiter comes to a stop on the runway. This control shall include the functions of vehicle management in the area of hardware configuration (verification), flight planning, communication and instrumentation configuration management, trajectory, software and consumables, payloads management, flight safety, and verification of test conditions/environment.

Down-regulation of RBP-J mediated by microRNA-133a suppresses dendritic cells and functions as a potential tumor suppressor in osteosarcoma.

PubMed

Gao, Xuren; Han, Dong; Fan, Weimin

2016-12-10

In recent years, immunotherapy for the treatment of tumors have been established. Dendritic cells (DCs) are extremely efficient and professional antigen presenting cells (APCs), which are an important target for immune therapeutic interventions in cancer. In present study, we investigated whether RBP-J signaling regulated by miR-133a was involved in the DCs mediated tumor suppressor in osteosarcoma. DCs were isolated from 30 osteosarcoma patients and 30 healthy subjects. Mouse macrophage-like cell line RAW264.7 were cultured and osteosarcoma mouse model with injection of murine osteosarcoma cell line S180 were established. In osteosarcoma patients, miR-133a expression level of DCs was increased, and RBP-J expression in mRNA and protein levels were decreased. MiR-133a inhibitor promoted maturation and activation of DCs in osteosarcoma patients. In osteosarcoma mouse model, miR-133a mimic suppressed the maturation and activation of spleen DCs, while miR-133a inhibitor promoted them. Overexpression of miR-133a decreased therapeutic effect of DCs on osteosarcoma mice. In RAW264.7 cells, miR-133a was observed to target RBP-J and regulate its expression. MiR-133a mimic inhibited the maturation of DCs in cells exposed to LPS, the effect of which was reversed by overexpression of RBP-J. RBP-J mediated by miR-133a probably contributed to the regulation of DCs maturation and activation in osteosarcoma, which functioned as a therapeutic target for the immunotherapy in cancers. Copyright © 2016. Published by Elsevier Inc.

Evidence-Based Approach to the Analysis of Serious Decompression Sickness with Application to EVA Astronauts

NASA Technical Reports Server (NTRS)

Conkin, Johnny

2001-01-01

It is important to understand the risk of serious hypobaric decompression sickness (DCS) in order to develop procedures and treatment responses to mitigate the risk. Since it is not ethical to conduct prospective tests about serious DCS with humans, the necessary information was gathered from 73 published reports. We hypothesize that a 4-hr 100% oxygen (O2) prebreathe results in a very low risk of serious DCS, and test this through analysis. We evaluated 258 tests containing information from 79,366 exposures in attitude chambers. Serious DCS was documented in 918 men during the tests. Serious DCS are signs and symptoms broadly classified as Type II DCS. A risk function analysis with maximum likelihood optimization was performed to identify significant explanatory variables, and to create a predictive model for the probability of serious DCS [P(serious DCS)]. Useful variables were Tissue Ratio, the planned time spent at altitude (T(sub alt)), and whether or not repetitive exercise was performed at altitude. Tissue Ratio is P1N2/P2, where P1N2 is calculated nitrogen (N2) pressure in a compartment with a 180-min half-time for N2 pressure just before ascent, and P2 is ambient pressure after ascent. A prebreathe and decompression profile Shuttle astronauts use for extravehicular activity (EVA) includes a 4-hr prebreathe with 100% O2, an ascent to P2 = 4.3 lb per sq. in. absolute, and a T(sub alt) = 6 hr. The P(serious DCS) is: 0.0014 (0.00096 - 0.00196, 95% confidence interval) with exercise and 0.00025 (0.00016 - 0.00035) without exercise. Given 100 Shuttle EVAs to date and no report of serious DCS, the true risk is less than 0.03 with 95% confidence (Binomial Theorem). It is problematic to estimate the risk of serious DCS since it appears infrequently, even if the estimate is based on thousands of altitude chamber exposures. The true risk to astronauts may lie between the extremes of the confidence intervals (0.00016 - 0.00196) since the contribution of other factors, particularly exercise, to the risk of serious DCS during EVA is unknown. A simple model that only accounts for four important variables in retrospective data is still helpful to increase our understanding about the risk of serious DCS.

Interactive associations of parental support, demands, and psychological control, over adolescents' beliefs about the legitimacy of parental authority.

PubMed

Mellado, Carlos; Cumsille, Patricio; Martínez, M Loreto

2018-04-01

The present study examined the relationship between parental support, demand, psychological control and adolescents' beliefs about the legitimacy of parental authority for personal and multifaceted issues in a sample of 1342 Chilean adolescents (M = 16.38, SD = 1.24, age range 14-20). Results from multiple regression analyses separated by age indicated that demand was positively associated with adolescents' beliefs about the legitimacy of parental authority for personal and multifaceted issues and that psychological control was negatively associated with adolescents' legitimacy beliefs concerning personal issues. Furthermore, parental support moderated the relationship between parental demand and adolescents' beliefs about parental legitimacy for personal and multifaceted issues: those who display high levels of demand showed stronger beliefs about parental legitimacy at high level of support. These results support the interactive effect of parental support and demand on adolescent development. Copyright © 2018. Published by Elsevier Ltd.

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

PubMed

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

2017-04-15

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

Effect of metabolic gases and water vapor, perfluorocarbon emulsions, and nitric oxide on tissue bubbles during decompression sickness.

PubMed

Randsøe, Thomas

2016-05-01

In aviation and diving, fast decrease in ambient pressure, such as during accidental loss of cabin pressure or when a diver decompresses too fast to sea level, may cause nitrogen (N2) bubble formation in blood and tissue resulting in decompression sickness (DCS). Conventional treatment of DCS is oxygen (O2) breathing combined with recompression.  However, bubble kinetic models suggest, that metabolic gases, i.e. O2 and carbon dioxide (CO2), and water vapor contribute significantly to DCS bubble volume and growth at hypobaric altitude exposures. Further, perfluorocarbon emulsions (PFC) and nitric oxide (NO) donors have, on an experimental basis, demonstrated therapeutic properties both as treatment and prophylactic intervention against DCS. The effect was ascribed to solubility of respiratory gases in PFC, plausible NO elicited nuclei demise and/or N2 washout through enhanced blood flow rate. Accordingly, by means of monitoring injected bubbles in exposed adipose tissue or measurements of spinal evoked potentials (SEPs) in anaesthetized rats, the aim of this study was to: 1) evaluate the contribution of metabolic gases and water vapor to bubble volume at different barometrical altitude exposures, 2) clarify the O2 contribution and N2 solubility from bubbles during administration of PFC at normo- and hypobaric conditions and, 3) test the effect of different NO donors on SEPs during DCS upon a hyperbaric air dive and, to study the influence of  NO on tissue bubbles at high altitude exposures. The results support the bubble kinetic models and indicate that metabolic gases and water vapor contribute significantly to bubble volume at 25 kPa (~10,376 m above sea level) and constitute a threshold for bubble stabilization or decay at the interval of 47-36 kPa (~6,036 and ~7,920 m above sea level). The effect of the metabolic gases and water vapor seemed to compromise the therapeutic properties of both PFC and NO at altitude, while PFC significantly increased bubble disappearance rate at sea level following a hyperbaric airdive. We found no protective effect of NO donors during DCS from diving. On the contrary, there was a tendency towards a poorer outcome when decompression was combined with NO donor administration. This observation is seemingly contradictive to recent publications and may be explained by the multifactorial effect of NO in combination with a fast decompression profile, speeding up the N2 release from tissues and thereby aggravating the DCS symptoms.

Tolerogenic Dendritic Cells Generated by In Vitro Treatment With SAHA Are Not Stable In Vivo.

PubMed

Thewissen, Kristof; Broux, Bieke; Hendriks, Jerome J A; Vanhees, Mandy; Stinissen, Piet; Slaets, Helena; Hellings, Niels

2016-01-01

The aim of this study is to examine whether the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), can generate dendritic cells (DCs) with a stable tolerogenic phenotype to counteract autoimmune responses in an animal model of multiple sclerosis. We investigated if the tolerogenic potency of DCs could be increased by continuous treatment during in vitro differentiation toward DCs compared to standard 24-h in vitro treatment of already terminally differentiated DCs. We show that in vitro treatment with SAHA reduces the generation of new CD11c(+) DCs out of mouse bone marrow. SAHA-generated DCs show reduced antigen-presenting function as evidenced by a reduction in myelin endocytosis, a decreased MHC II expression, and a failure to upregulate costimulatory molecules upon LPS challenge. In addition, SAHA-generated DCs display a reduction in proinflammatory cytokines and molecules involved in apoptosis induction, inflammatory migration, and TLR signaling, and they are less immunostimulatory compared to untreated DCs. We demonstrated that the underlying mechanism involves a diminished STAT1 phosphorylation and was independent of STAT6 activation. Although in vitro results were promising, SAHA-generated DCs were not able to alleviate the development of experimental autoimmune encephalomyelitis in mice. In vitro washout experiments demonstrated that the tolerogenic phenotype of SAHA-treated DCs is reversible. Taken together, while SAHA potently boosts tolerogenic properties in DCs during the differentiation process in vitro, SAHA-generated DCs were unable to reduce autoimmunity in vivo. Our results imply that caution needs to be taken when developing DC-based therapies to induce tolerance in the context of autoimmune disease.

Dynamic Control System Mode Performance of the Space Technology-7 Disturbance Reduction System

NASA Technical Reports Server (NTRS)

O'Donnell, James R., Jr.; Hsu, Oscar; Maghami, Peiman

2017-01-01

The Space Technology-7 (ST-7) Disturbance Reduction System (DRS) is an experiment package aboard the European Space Agency (ESA) LISA Pathfinder spacecraft, launched on December 3, 2015. DRS consists of three primary components: Colloidal MicroNewton Thrusters (CMNTs), an Integrated Avionics Unit (IAU), and flight-software implementing the Command and Data Handling (C&DH) and Dynamic Control System (DCS) algorithms. The CMNTs were designed to provide thrust from 5 to 30 micro Newton, with thrust controllability and resolution of 0.1 micro Newton and thrust noise of 0.1 micro Newton/(square root of (Hz)) in the measurement band from 1-30 mHz. The IAU hosts the C&DH and DCS flight software, as well as interfaces with both the CMNT electronics and the LISA Pathfinder spacecraft. When in control, the DCS uses star tracker attitude data and capacitive or optically-measured position and attitude information from LISA Pathfinder and the LISA Technology Package (LTP) to control the attitude and position of the spacecraft and the two test masses inside the LTP. After completion of the nominal ESA LISA Pathfinder mission, the DRS experiment was commissioned followed by its nominal mission. DRS operations extended over the next five months, interspersed with station keeping, anomaly resolution, and periods where control was handed back to LISA Pathfinder for them to conduct further experiments. The primary DRS mission ended on December 6, 2016, with the experiment meeting all of its Level 1 requirements. The DCS, developed at the NASA Goddard Space Flight Center, consists of five spacecraft control modes and six test mass control modes, combined into six 'DRS Mission Modes'. Attitude Control and Zero-G were primarily used to control the spacecraft during initial handover and during many of the CMNT characterization experiments. The other Mission Modes, Drag Free Low Force, 18-DOF Transitional, and 18-DOF, were used to provide drag-free control of the spacecraft about the test masses. This paper will discuss the performance of these DCS spacecraft and test mass control modes. Flight data will be shown from each mode throughout the mission, both from nominal operations and during various flight experiments. The DCS team also made some changes to controller, filter, and limit parameters during operations; the motivation and results of these changes will be shown and discussed.

Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

PubMed

Datta, Abhishek; Baker, Julie M; Bikson, Marom; Fridriksson, Julius

2011-07-01

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here. Copyright © 2011 Elsevier Inc. All rights reserved.

Polysaccharide purified from Ganoderma atrum induced activation and maturation of murine myeloid-derived dendritic cells.

PubMed

Wang, Hui; Yu, Qiang; Nie, Shao-Ping; Xiang, Quan-Dan; Zhao, Ming-Ming; Liu, Shi-Yu; Xie, Ming-Yong; Wang, Shun-Qi

2017-10-01

Ganoderma atrum (G. atrum), a member of the genus Ganoderma, is an edible and medicinal fungus. In this study, we investigated the direct and indirect effects of G. atrum polysaccharide (PSG-1) on dendritic cells (DCs). Firstly, flow cytometric and ELISA analysis showed that PSG-1 increased cell surface molecule expression of MHC-II, CD80 and CD86, and enhanced the production of IL-12 p70, IL-6, IL-10, RANTES, MIP-1α and MCP-1 in DCs. PSG-1-treated DCs promoted the proliferation of splenic T lymphocyte of mouse in mixed lymphocyte reaction. The above results demonstrated that PSG-1 induced the maturation of DCs. Secondly, PSG-1 increased the phosphorylation of p38, ERK and JNK determined by western blot. Inhibitors of p38, ERK and JNK decreased PSG-1-induced expression of MHC-II, CD80 and CD86 and production of IL-6 and IL-10 by DCs. These results suggested that PSG-1 induced mitogen-activated protein kinase (MAPK) activation was involved in the regulation of maturation markers and cytokines expression in DCs. Finally, PSG-1 increased expression of MHC-II of DCs in a DCs-Caco-2 co-culture model, suggesting that PSG-1 could indirectly influence DCs. In summary, our data suggested that PSG-1 directly induced DCs maturation via activating MAPK pathways, and indirectly stimulated DCs separated by intestinal epithelial cells. Copyright © 2017. Published by Elsevier Ltd.

Effect of sialic acid loss on dendritic cell maturation

PubMed Central

Crespo, Hélio J; Guadalupe Cabral, M; Teixeira, Alexandra V; Lau, Joseph T Y; Trindade, Hélder; Videira, Paula A

2009-01-01

Sialic acids are key structural determinants and contribute to the functionality of a number of immune cell receptors. Previously, we demonstrated that differentiation of human dendritic cells (DCs) is accompanied by an increased expression of sialylated cell surface structures, putatively through the activity of the ST3Gal.I and ST6Gal.I sialyltransferases. Furthermore, DC endocytosis was reduced upon removal of the cell surface sialic acid residues by neuraminidase. In the present work, we evaluate the contribution of the sialic acid modifications in DC maturation. We demonstrate that neuraminidase-treated human DCs have increased expression of major histocompatibility complex (MHC) and costimulatory molecules, increased gene expression of specific cytokines and induce a higher proliferative response of T lymphocytes. Together, the data suggest that clearance of cell surface sialic acids contributes to the development of a T helper type 1 proinflammatory response. This postulate is supported by mouse models, where elevated MHC class II and increased maturation of specific DC subsets were observed in DCs harvested from ST3Gal.I−/− and ST6Gal.I−/− mice. Moreover, important qualitative differences, particularly in the extent of reduced endocytosis and in the peripheral distribution of DC subsets, existed between the ST3Gal.I−/− and ST6Gal.I−/− strains. Together, the data strongly suggest not only a role of cell surface sialic acid modifications in maturation and functionality of DCs, but also that the sialic acid linkages created by different sialyltransferases are functionally distinct. Consequently, with particular relevance to DC-based therapies, cell surface sialylation, mediated by individual sialyltransferases, can influence the immunogenicity of DCs upon antigen loading. PMID:19740323

Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review.

PubMed

Kim, Minah; Kwak, Yoo Bin; Lee, Tae Young; Kwon, Jun Soo

2018-04-27

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique increasingly used to relieve symptoms of psychiatric disorders. Electrophysiologic markers, such as electroencephalography (EEG) and event-related potentials (ERP), have high temporal resolution sensitive to detect plastic changes of the brain associated with symptomatic improvement following tDCS application. We performed systematic review to identify electrophysiological markers that reflect tDCS effects on plastic brain changes in psychiatric disorders. A total of 638 studies were identified by searching PubMed, Embase, psychINFPO. Of these, 21 full-text articles were assessed eligible and included in the review. Although the reviewed studies were heterogeneous in their choices of tDCS protocols, targeted electrophysiological markers, and disease entities, their results strongly support EEG/ERPs to sensitively reflect plastic brain changes and the associated symptomatic improvement following tDCS. EEG/ERPs may serve a potent tool in revealing the mechanisms underlying psychiatric symptoms, as well as in localizing the brain area targeted for stimulation. Future studies in each disease entities employing consistent tDCS protocols and electrophysiological markers would be necessary in order to substantiate and further elaborate the findings of studies included in the present systematic review.

Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells.

PubMed

Montoya, Carlos J; Jie, Hyun-Bae; Al-Harthi, Lena; Mulder, Candice; Patiño, Pablo J; Rugeles, María T; Krieg, Arthur M; Landay, Alan L; Wilson, S Brian

2006-07-15

CD1d-restricted invariant NK T (iNKT) cells and dendritic cells (DCs) have been shown to play crucial roles in various types of immune responses, including TLR9-dependent antiviral responses initiated by plasmacytoid DCs (pDCs). However, the mechanism by which this occurs is enigmatic because TLRs are absent in iNKT cells and human pDCs do not express CD1d. To explore this process, pDCs were activated with CpG oligodeoxyribonucleotides, which stimulated the secretion of several cytokines such as type I and TNF-alpha. These cytokines and other soluble factors potently induced the expression of activation markers on iNKT cells, selectively enhanced double-negative iNKT cell survival, but did not induce their expansion or production of cytokines. Notably, pDC-derived factors licensed iNKT cells to respond to myeloid DCs: an important downstream cellular target of iNKT cell effector function and a critical contributor to the initiation of adaptive immune responses. This interaction supports the notion that iNKT cells can mediate cross-talk between DC subsets known to express mutually exclusive TLR and cytokine profiles.

Incorporating location, routing, and inventory decisions in a bi-objective supply chain design problem with risk-pooling

NASA Astrophysics Data System (ADS)

Tavakkoli-Moghaddam, Reza; Forouzanfar, Fateme; Ebrahimnejad, Sadoullah

2013-07-01

This paper considers a single-sourcing network design problem for a three-level supply chain. For the first time, a novel mathematical model is presented considering risk-pooling, the inventory existence at distribution centers (DCs) under demand uncertainty, the existence of several alternatives to transport the product between facilities, and routing of vehicles from distribution centers to customer in a stochastic supply chain system, simultaneously. This problem is formulated as a bi-objective stochastic mixed-integer nonlinear programming model. The aim of this model is to determine the number of located distribution centers, their locations, and capacity levels, and allocating customers to distribution centers and distribution centers to suppliers. It also determines the inventory control decisions on the amount of ordered products and the amount of safety stocks at each opened DC, selecting a type of vehicle for transportation. Moreover, it determines routing decisions, such as determination of vehicles' routes starting from an opened distribution center to serve its allocated customers and returning to that distribution center. All are done in a way that the total system cost and the total transportation time are minimized. The Lingo software is used to solve the presented model. The computational results are illustrated in this paper.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2014-12-01

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

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

PubMed

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

2018-07-01

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

Dendritic cell control of tolerogenic responses

PubMed Central

Manicassamy, Santhakumar; Pulendran, Bali

2011-01-01

Summary One of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body’s own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. A fundamental role for the innate immune system, particularly dendritic cells (DCs), in orchestrating immunological tolerance has been appreciated, but emerging studies have highlighted the nature of the innate receptors and the signaling pathways that program DCs to a tolerogenic state. Furthermore, several studies have emphasized the major role played by cellular interactions, and the microenvironment in programming tolerogenic DCs. Here we review these studies and suggest that the innate control of tolerogenic responses can be viewed as different hierarchies of organization, in which DCs, their innate receptors and signaling networks, and their interactions with other cells and local microenvironments represent different levels of the hierarchy. PMID:21488899

The impact of social and organizational factors on workers' use of personal protective equipment: a multilevel approach.

PubMed

Torp, Steffen; Grøgaard, Jens B; Moen, Bente E; Bråtveit, Magne

2005-08-01

On the basis of the job demands-control-support model by Karasek and Theorell, we investigated how social and organizational factors influence workers' use of personal protective equipment (PPE). A cross-sectional study was performed among 1420 workers in 203 motor vehicle-repair garages. Multilevel modeling was performed to account for the hierarchical structure of the data. Social and management support correlated positively with PPE use at the worker level. Low demands measured at the garage level and having a health and safety management system at the garage also correlated with active use of PPE. An interaction effect between social support and garage-level demands was observed. In addition to health information and provision of PPE, focusing on social and organizational factors seems necessary to get more workers to comply with the instructions on PPE use.

Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo

PubMed Central

Laperchia, Claudia; Allegra Mascaro, Anna L.; Sacconi, Leonardo; Andrioli, Anna; Mattè, Alessandro; De Franceschi, Lucia; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Buffelli, Mario; Pavone, Francesco S.

2013-01-01

Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions. PMID:23409142

Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender.

PubMed

Meiron, Oded; Lavidor, Michal

2013-05-01

Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory representations in interference-rich conditions, and is highly dependent on DLPFC function. We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined "online" WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Experimental analysis and modeling of ultrasound assisted freezing of potato spheres.

PubMed

Kiani, Hossein; Zhang, Zhihang; Sun, Da-Wen

2015-09-01

In recent years, innovative methods such as ultrasound assisted freezing have been developed in order to improve the freezing process. During freezing of foods, accurate prediction of the temperature distribution, phase ratios, and process time is very important. In the present study, ultrasound assisted immersion freezing process (in 1:1 ethylene glycol-water solution at 253.15K) of potato spheres (0.02 m diameter) was evaluated using experimental, numerical and analytical approaches. Ultrasound (25 kHz, 890 W m(-2)) was irradiated for different duty cycles (DCs=0-100%). A finite volume based enthalpy method was used in the numerical model, based on which temperature and liquid fraction profiles were simulated by a program developed using OpenFOAM® CFD software. An analytical technique was also employed to calculate freezing times. The results showed that ultrasound irradiation could decrease the characteristic freezing time of potatoes. Since ultrasound irradiation increased the heat transfer coefficient but simultaneously generated heat at the surface of the samples, an optimum DC was needed for the shortest freezing time which occurred in the range of 30-70% DC. DCs higher than 70% increased the freezing time. DCs lower than 30% did not provide significant effects on the freezing time compared to the control sample. The numerical model predicted the characteristic freezing time in accordance with the experimental results. In addition, analytical calculation of characteristic freezing time exhibited qualitative agreement with the experimental results. As the numerical simulations provided profiles of temperature and water fraction within potatoes frozen with or without ultrasound, the models can be used to study and control different operation situations, and to improve the understanding of the freezing process. Copyright © 2015 Elsevier B.V. All rights reserved.

The diffuse chemosensory system: exploring the iceberg toward the definition of functional roles.

PubMed

Sbarbati, Andrea; Bramanti, Placido; Benati, Donatella; Merigo, Flavia

2010-05-01

The diffuse chemosensory system (DCS) is an anatomical structure composed of solitary chemosensory cells (SCCs, also called solitary chemoreceptor cells), which have analogies with taste cells but are not aggregated in buds. The concept of DCS has been advanced, after the discovery that cells similar to gustatory elements are present in several organs. The elements forming the DCS share common morphological and biochemical characteristics with the taste cells located in taste buds of the oro-pharyngeal cavity but they are localized in internal organs. In particular, they may express molecules of the chemoreceptorial cascade (e.g. trans-membrane taste receptors, the G-protein alpha-gustducin, PLCbeta2, TRPM5). This article will focus on the mammalian DCS in apparatuses of endodermic origin (i.e. digestive and respiratory systems), which is composed of an enormous number of sensory elements and presents a multiplicity of morphological aspects. Recent research has provided an adequate description of these elements, but the functional role for the DCS in these apparatuses is unknown. The initial findings led to the definition of a DCS structured like an iceberg, with a mysterious "submerged" portion localized in the distal part of endodermic apparatuses. Recent work has focussed on the discovery of this submerged portion, which now appears less puzzling. However, the functional roles of the different cytotypes belonging to the DCS are not well known. Recent studies linked chemosensation of the intraluminal content to local control of absorptive and secretory (exocrine and endocrine) processes. Control of the microbial population and detection of irritants seem to be other possible functions of the DCS. In the light of these new findings, the DCS might be thought to be involved in a wide range of diseases of both the respiratory (e.g. asthma, chronic obstructive pulmonary disease, cystic fibrosis) and digestive apparatuses (absorptive or secretive diseases, dysmicrobism), as well as in systemic diseases (e.g. obesity, diabetes). A description of the functional roles of the DCS might be a first step toward the discovery of therapeutic approaches which target chemosensory mechanisms. Copyright 2010 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-04-01

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

Synergistic interaction between job control and social support at work on depression, burnout, and insomnia among Japanese civil servants.

PubMed

Saijo, Yasuaki; Chiba, Shigeru; Yoshioka, Eiji; Nakagi, Yoshihiko; Ito, Toshihiro; Kitaoka-Higashiguchi, Kazuyo; Yoshida, Takahiko

2015-02-01

To elucidate whether low job control and low social support at work have synergistic interaction on mental health. The synergistic interaction was also analyzed after stratification by high and low job demands. Participants were 2,121 local government employees in Asahikawa city, Japan. The Brief Job Stress Questionnaire was used to assess job demands, job control, and social support. Depression was assessed using the Patient Health Questionnaire-9. The Maslach Burnout Inventory-General Survey was used to assess burnout. Insomnia was assessed using the Athens Insomnia Scale. Possible confounder-adjusted logistic regression analyses were performed to obtain odds ratios for depression, burnout, and insomnia, and synergy indices between job control and social support at work were assessed. The synergy indices among men and women, respectively, were 2.08 (80 % confidence interval: 1.01, 4.27) and 1.98 (0.67, 5.89) for depression, 1.79 (1.28, 2.51) and 2.62 (1.07, 6.40) for burnout, and 1.92 (1.22, 3.02) and 2.77 (0.43, 18.01) for insomnia. Men with high job demands had higher synergistic interaction on depression and burnout, compared to men with low job demands, and women with low job demands had higher synergistic interaction between job control and social support at work on burnout and insomnia, compared to women with high job demands. There were more-than-additive interactions of job control and social support at work on depression, burnout, and insomnia. After stratification by job demands, the synergistic interaction may be different between men and women. To assess job stress, it is necessary to consider the interactive effect of not only job demands and job control but also job control and social support at work.

Visualization of historical data for the ATLAS detector controls - DDV

NASA Astrophysics Data System (ADS)

Maciejewski, J.; Schlenker, S.

2017-10-01

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

Working conditions, self-perceived stress, anxiety, depression and quality of life: A structural equation modelling approach

PubMed Central

Rusli, Bin Nordin; Edimansyah, Bin Abdin; Naing, Lin

2008-01-01

Background The relationships between working conditions [job demand, job control and social support]; stress, anxiety, and depression; and perceived quality of life factors [physical health, psychological wellbeing, social relationships and environmental conditions] were assessed using a sample of 698 male automotive assembly workers in Malaysia. Methods The validated Malay version of the Job Content Questionnaire (JCQ), Depression Anxiety Stress Scales (DASS) and the World Health Organization Quality of Life-Brief (WHOQOL-BREF) were used. A structural equation modelling (SEM) analysis was applied to test the structural relationships of the model using AMOS version 6.0, with the maximum likelihood ratio as the method of estimation. Results The results of the SEM supported the hypothesized structural model (χ2 = 22.801, df = 19, p = 0.246). The final model shows that social support (JCQ) was directly related to all 4 factors of the WHOQOL-BREF and inversely related to depression and stress (DASS). Job demand (JCQ) was directly related to stress (DASS) and inversely related to the environmental conditions (WHOQOL-BREF). Job control (JCQ) was directly related to social relationships (WHOQOL-BREF). Stress (DASS) was directly related to anxiety and depression (DASS) and inversely related to physical health, environment conditions and social relationships (WHOQOL-BREF). Anxiety (DASS) was directly related to depression (DASS) and inversely related to physical health (WHOQOL-BREF). Depression (DASS) was inversely related to the psychological wellbeing (WHOQOL-BREF). Finally, stress, anxiety and depression (DASS) mediate the relationships between job demand and social support (JCQ) to the 4 factors of WHOQOL-BREF. Conclusion These findings suggest that higher social support increases the self-reported quality of life of these workers. Higher job control increases the social relationships, whilst higher job demand increases the self-perceived stress and decreases the self-perceived quality of life related to environmental factors. The mediating role of depression, anxiety and stress on the relationship between working conditions and perceived quality of life in automotive workers should be taken into account in managing stress amongst these workers. PMID:18254966

Working conditions, self-perceived stress, anxiety, depression and quality of life: a structural equation modelling approach.

PubMed

Rusli, Bin Nordin; Edimansyah, Bin Abdin; Naing, Lin

2008-02-06

The relationships between working conditions [job demand, job control and social support]; stress, anxiety, and depression; and perceived quality of life factors [physical health, psychological wellbeing, social relationships and environmental conditions] were assessed using a sample of 698 male automotive assembly workers in Malaysia. The validated Malay version of the Job Content Questionnaire (JCQ), Depression Anxiety Stress Scales (DASS) and the World Health Organization Quality of Life-Brief (WHOQOL-BREF) were used. A structural equation modelling (SEM) analysis was applied to test the structural relationships of the model using AMOS version 6.0, with the maximum likelihood ratio as the method of estimation. The results of the SEM supported the hypothesized structural model (chi2 = 22.801, df = 19, p = 0.246). The final model shows that social support (JCQ) was directly related to all 4 factors of the WHOQOL-BREF and inversely related to depression and stress (DASS). Job demand (JCQ) was directly related to stress (DASS) and inversely related to the environmental conditions (WHOQOL-BREF). Job control (JCQ) was directly related to social relationships (WHOQOL-BREF). Stress (DASS) was directly related to anxiety and depression (DASS) and inversely related to physical health, environment conditions and social relationships (WHOQOL-BREF). Anxiety (DASS) was directly related to depression (DASS) and inversely related to physical health (WHOQOL-BREF). Depression (DASS) was inversely related to the psychological wellbeing (WHOQOL-BREF). Finally, stress, anxiety and depression (DASS) mediate the relationships between job demand and social support (JCQ) to the 4 factors of WHOQOL-BREF. These findings suggest that higher social support increases the self-reported quality of life of these workers. Higher job control increases the social relationships, whilst higher job demand increases the self-perceived stress and decreases the self-perceived quality of life related to environmental factors. The mediating role of depression, anxiety and stress on the relationship between working conditions and perceived quality of life in automotive workers should be taken into account in managing stress amongst these workers.

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

PubMed

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

2017-01-08

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

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

PubMed Central

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

2018-01-01

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

Modelling ultrasound guided wave propagation for plate thickness measurement

NASA Astrophysics Data System (ADS)

Malladi, Rakesh; Dabak, Anand; Murthy, Nitish Krishna

2014-03-01

Structural Health monitoring refers to monitoring the health of plate-like walls of large reactors, pipelines and other structures in terms of corrosion detection and thickness estimation. The objective of this work is modeling the ultrasonic guided waves generated in a plate. The piezoelectric is excited by an input pulse to generate ultrasonic guided lamb waves in the plate that are received by another piezoelectric transducer. In contrast with existing methods, we develop a mathematical model of the direct component of the signal (DCS) recorded at the terminals of the piezoelectric transducer. The DCS model uses maximum likelihood technique to estimate the different parameters, namely the time delay of the signal due to the transducer delay and amplitude scaling of all the lamb wave modes due to attenuation, while taking into account the received signal spreading in time due to dispersion. The maximum likelihood estimate minimizes the energy difference between the experimental and the DCS model-generated signal. We demonstrate that the DCS model matches closely with experimentally recorded signals and show it can be used to estimate thickness of the plate. The main idea of the thickness estimation algorithm is to generate a bank of DCS model-generated signals, each corresponding to a different thickness of the plate and then find the closest match among these signals to the received signal, resulting in an estimate of the thickness of the plate. Therefore our approach provides a complementary suite of analytics to the existing thickness monitoring approaches.

Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines☆

PubMed Central

Truong, Dennis Q.; Magerowski, Greta; Blackburn, George L.; Bikson, Marom; Alonso-Alonso, Miguel

2013-01-01

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from “normal-lean” to “super-obese” (20.9 to 53.5 kg/m2). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population. PMID:24159560

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

PubMed

Cattaneo, Z; Pisoni, A; Papagno, C

2011-06-02

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

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.

PubMed

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.

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

PubMed

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

2017-05-01

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

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

PubMed

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 (P<0.05), whereas only group 2W obtained a significant improvement in the RR ratio compared with the control group (P<0.05). However, there were no significant differences between any of the groups at five weeks after TBI. Immunohistochemistry revealed that only group 2W had a significantly higher brain-derived neurotrophic factor (BDNF) expression in the peri-lesional cortex, which was significantly correlated with the improvement of the Rotarod test at 3-week post-injury. However, BDNF expression in the ipsi-lesional hippocampus was not significantly different among the three groups. Group 1W tended to have increased choline/creatine ratios, as measured by magnetic resonance spectroscopy in the peri-lesional cortex, than the control group (P=0.051). Neither regimen aggravated the lesion volume or brain edema measured by MRI. These beneficial effects were not observed with either regimen at five weeks post-injury. In conclusions, anodal tDCS 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.

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

PubMed

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

2018-05-04

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

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

PubMed

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

2015-02-19

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

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

PubMed

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

2017-08-01

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

New measure for fathers of children with developmental challenges.

PubMed

Ly, A R; Goldberg, W A

2014-05-01

There is a relative lack of measures tailored to the study of fathers of children with developmental challenges (DCs). The goal of the current study was to create and validate a brief measure designed to capture the perceptions and experiences of these fathers. The Fathers of Children with Developmental Challenges (FCDC) questionnaire was designed to assess fathers' perceptions of the supports for, and challenges to, their efforts to be involved in the rearing of their children. Participants were 101 fathers of children with DCs who completed an online survey. Scale validation included tests to determine reliability, validity and factor structure. Used to establish validity were measures of parenting stress, parenting commitment, parent personality and child social-communicative skills. Analyses indicated that the FCDC is reliable (α = 0.89), demonstrates content validity, construct validity and acts in theoretically expected ways. Factor analysis on the 20-item measure yielded two sub-scales: (1) impact on parenting, and (2) involvement with child intervention. The FCDC fills a gap in the literature by offering an easy-to-administer self-report measure of fathers' perceptions of supports for, and barriers to, their involvement with their children with DCs. The FCDC could assist professionals in delivering support services specifically for fathers of children with DCs. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

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

PubMed Central

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. PMID:29558513

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

PubMed

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.

Oscillating square wave Transcranial Direct Current Stimulation (tDCS) delivered during slow wave sleep does not improve declarative memory more than sham: A randomized sham controlled crossover study

PubMed Central

Sahlem, Gregory L.; Badran, Bashar W.; Halford, Jonathan J.; Williams, Nolan R.; Korte, Jeffrey E.; Leslie, Kimberly; Strachan, Martha; Breedlove, Jesse L.; Runion, Jennifer; Bachman, David L.; Uhde, Thomas W.; Borckardt, Jeffery J.; George, Mark S.

2015-01-01

Background A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current wave form (square in our study, nearly sinusoidal in the original). Objective/Hypothesis Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Methods Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517mA/CM2, and oscillated between zero and maximal current at a frequency of 0.75Hz. Stimulation occurred during five-five minute blocks with one-minute inter-block intervals (25 minutes total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. Results There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1±3.0SD more associations) (sham = 3.8±3.1S.D more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6±2.7 S.D. correctly typed sequences) compared to sham stimulation (2.3± 2.2 S.D. correctly typed sequences)]. Conclusion In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements. PMID:25795621

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

PubMed

Sahlem, Gregory L; Badran, Bashar W; Halford, Jonathan J; Williams, Nolan R; Korte, Jeffrey E; Leslie, Kimberly; Strachan, Martha; Breedlove, Jesse L; Runion, Jennifer; Bachman, David L; Uhde, Thomas W; Borckardt, Jeffery J; George, Mark S

2015-01-01

A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed sequences)]. In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements. Copyright © 2015 Elsevier Inc. All rights reserved.