Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

NASA Astrophysics Data System (ADS)

Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

2017-06-01

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

Development of a hybrid broadband NIRS/diffusion correlation spectroscopy system to monitor preterm brain injury (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rajaram, Ajay; St. Lawrence, Keith; Diop, Mamadou

2017-02-01

In Canada, 8% of births occur prematurely. Preterm infants weighing less than 1500g are at a high risk of neurodevelopmental impairment: 5-10% develop major disabilities such as cerebral palsy and 40-50% show other cognitive and behavioural deficits. The brain is vulnerable to periods of low cerebral blood flow (CBF) that can impair energy metabolism and cause tissue damage. There is, therefore, a need for an efficient neuromonitoring system to alert the neonatal intensive care team to clinically significant changes in CBF and metabolism, before injury occurs. Optical technologies offer safe, non-invasive, and cost-effective methods for neuromonitoring. Cerebral oxygen saturation (ScO2) can be measured by exploiting the absorption properties of hemoglobin though Near-Infrared Spectroscopy (NIRS), and Diffuse Correlation Spectroscopy (DCS) can monitor CBF by tracking red blood cells. These measures can be combined to describe metabolism, a key indicator of tissue viability. In this study we present the development and testing of a hybrid broadband NIRS/DCS neuromonitor. This system is novel in its ability to simultaneously acquire broadband NIRS and DCS signals, providing a truly real-time measure of metabolism. Narrow bandpass and notch filters have been incorporated to diminish light contamination between the two modalities, preferentially filtering out each source from the opposing detector, allowing for an accurate measure of ScO2, CBF, and metabolism. With a broadband NIRS/DCS system, a real-time measure of CBF and metabolism within the developing brain can aid clinicians in monitoring events that precede brain injury, ultimately leading to better clinical outcomes.

Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts.

PubMed

Baker, Wesley B; Parthasarathy, Ashwin B; Ko, Tiffany S; Busch, David R; Abramson, Kenneth; Tzeng, Shih-Yu; Mesquita, Rickson C; Durduran, Turgut; Greenberg, Joel H; Kung, David K; Yodh, Arjun G

2015-07-01

We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm's ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.

Fast blood flow monitoring in deep tissues with real-time software correlators

PubMed Central

Wang, Detian; Parthasarathy, Ashwin B.; Baker, Wesley B.; Gannon, Kimberly; Kavuri, Venki; Ko, Tiffany; Schenkel, Steven; Li, Zhe; Li, Zeren; Mullen, Michael T.; Detre, John A.; Yodh, Arjun G.

2016-01-01

We introduce, validate and demonstrate a new software correlator for high-speed measurement of blood flow in deep tissues based on diffuse correlation spectroscopy (DCS). The software correlator scheme employs standard PC-based data acquisition boards to measure temporal intensity autocorrelation functions continuously at 50 – 100 Hz, the fastest blood flow measurements reported with DCS to date. The data streams, obtained in vivo for typical source-detector separations of 2.5 cm, easily resolve pulsatile heart-beat fluctuations in blood flow which were previously considered to be noise. We employ the device to separate tissue blood flow from tissue absorption/scattering dynamics and thereby show that the origin of the pulsatile DCS signal is primarily flow, and we monitor cerebral autoregulation dynamics in healthy volunteers more accurately than with traditional instrumentation as a result of increased data acquisition rates. Finally, we characterize measurement signal-to-noise ratio and identify count rate and averaging parameters needed for optimal performance. PMID:27231588

Establishing the diffuse correlation spectroscopy signal relationship with blood flow.

PubMed

Boas, David A; Sakadžić, Sava; Selb, Juliette; Farzam, Parisa; Franceschini, Maria Angela; Carp, Stefan A

2016-07-01

Diffuse correlation spectroscopy (DCS) measurements of blood flow rely on the sensitivity of the temporal autocorrelation function of diffusively scattered light to red blood cell (RBC) mean square displacement (MSD). For RBCs flowing with convective velocity [Formula: see text], the autocorrelation is expected to decay exponentially with [Formula: see text], where [Formula: see text] is the delay time. RBCs also experience shear-induced diffusion with a diffusion coefficient [Formula: see text] and an MSD of [Formula: see text]. Surprisingly, experimental data primarily reflect diffusive behavior. To provide quantitative estimates of the relative contributions of convective and diffusive movements, we performed Monte Carlo simulations of light scattering through tissue of varying vessel densities. We assumed laminar vessel flow profiles and accounted for shear-induced diffusion effects. In agreement with experimental data, we found that diffusive motion dominates the correlation decay for typical DCS measurement parameters. Furthermore, our model offers a quantitative relationship between the RBC diffusion coefficient and absolute tissue blood flow. We thus offer, for the first time, theoretical support for the empirically accepted ability of the DCS blood flow index ([Formula: see text]) to quantify tissue perfusion. We find [Formula: see text] to be linearly proportional to blood flow, but with a proportionality modulated by the hemoglobin concentration and the average blood vessel diameter.

EEG-NIRS based assessment of neurovascular coupling during anodal transcranial direct current stimulation--a stroke case series.

PubMed

Dutta, Anirban; Jacob, Athira; Chowdhury, Shubhajit Roy; Das, Abhijit; Nitsche, Michael A

2015-04-01

A method for electroencephalography (EEG) - near-infrared spectroscopy (NIRS) based assessment of neurovascular coupling (NVC) during anodal transcranial direct current stimulation (tDCS). Anodal tDCS modulates cortical neural activity leading to a hemodynamic response, which was used to identify impaired NVC functionality. In this study, the hemodynamic response was estimated with NIRS. NIRS recorded changes in oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) concentrations during anodal tDCS-induced activation of the cortical region located under the electrode and in-between the light sources and detectors. Anodal tDCS-induced alterations in the underlying neuronal current generators were also captured with EEG. Then, a method for the assessment of NVC underlying the site of anodal tDCS was proposed that leverages the Hilbert-Huang Transform. The case series including four chronic (>6 months) ischemic stroke survivors (3 males, 1 female from age 31 to 76) showed non-stationary effects of anodal tDCS on EEG that correlated with the HbO2 response. Here, the initial dip in HbO2 at the beginning of anodal tDCS corresponded with an increase in the log-transformed mean-power of EEG within 0.5Hz-11.25Hz frequency band. The cross-correlation coefficient changed signs but was comparable across subjects during and after anodal tDCS. The log-transformed mean-power of EEG lagged HbO2 response during tDCS but then led post-tDCS. This case series demonstrated changes in the degree of neurovascular coupling to a 0.526 A/m(2) square-pulse (0-30 s) of anodal tDCS. The initial dip in HbO2 needs to be carefully investigated in a larger cohort, for example in patients with small vessel disease.

Modified Beer-Lambert law for blood flow

NASA Astrophysics Data System (ADS)

Baker, Wesley B.; Parthasarathy, Ashwin B.; Busch, David R.; Mesquita, Rickson C.; Greenberg, Joel H.; Yodh, A. G.

2015-03-01

The modified Beer-Lambert law is among the most widely used approaches for analysis of near-infrared spectroscopy (NIRS) reflectance signals for measurements of tissue blood volume and oxygenation. Briefly, the modified Beer-Lambert paradigm is a scheme to derive changes in tissue optical properties based on continuous-wave (CW) diffuse optical intensity measurements. In its simplest form, the scheme relates differential changes in light transmission (in any geometry) to differential changes in tissue absorption. Here we extend this paradigm to the measurement of tissue blood flow by diffuse correlation spectroscopy (DCS). In the new approach, differential changes of the intensity temporal auto-correlation function at a single delay-time are related to differential changes in blood flow. The key theoretical results for measurement of blood flow changes in any tissue geometry are derived, and we demonstrate the new method to monitor cerebral blood flow in a pig under conditions wherein the semi-infinite geometry approximation is fairly good. Specifically, the drug dinitrophenol was injected in the pig to induce a gradual 200% increase in cerebral blood flow, as measured with MRI velocity flow mapping and by DCS. The modified Beer-Lambert law for flow accurately recovered these flow changes using only a single delay-time in the intensity auto-correlation function curve. The scheme offers increased DCS measurement speed of blood flow. Further, the same techniques using the modified Beer-Lambert law to filter out superficial tissue effects in NIRS measurements of deep tissues can be applied to the DCS modified Beer-Lambert law for blood flow monitoring of deep tissues.

Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts

PubMed Central

Baker, Wesley B.; Parthasarathy, Ashwin B.; Ko, Tiffany S.; Busch, David R.; Abramson, Kenneth; Tzeng, Shih-Yu; Mesquita, Rickson C.; Durduran, Turgut; Greenberg, Joel H.; Kung, David K.; Yodh, Arjun G.

2015-01-01

Abstract. We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm’s ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy. PMID:26301255

Extraction of diffuse correlation spectroscopy flow index by integration of Nth-order linear model with Monte Carlo simulation

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

Shang, Yu; Lin, Yu; Yu, Guoqiang, E-mail: guoqiang.yu@uky.edu

2014-05-12

Conventional semi-infinite solution for extracting blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements may cause errors in estimation of BFI (αD{sub B}) in tissues with small volume and large curvature. We proposed an algorithm integrating Nth-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in tissue for the extraction of αD{sub B}. The volume and geometry of the measured tissue were incorporated in the Monte Carlo simulation, which overcome the semi-infinite restrictions. The algorithm was tested using computer simulations on four tissue models with varied volumes/geometries and applied on an in vivo strokemore » model of mouse. Computer simulations shows that the high-order (N ≥ 5) linear algorithm was more accurate in extracting αD{sub B} (errors < ±2%) from the noise-free DCS data than the semi-infinite solution (errors: −5.3% to −18.0%) for different tissue models. Although adding random noises to DCS data resulted in αD{sub B} variations, the mean values of errors in extracting αD{sub B} were similar to those reconstructed from the noise-free DCS data. In addition, the errors in extracting the relative changes of αD{sub B} using both linear algorithm and semi-infinite solution were fairly small (errors < ±2.0%) and did not rely on the tissue volume/geometry. The experimental results from the in vivo stroke mice agreed with those in simulations, demonstrating the robustness of the linear algorithm. DCS with the high-order linear algorithm shows the potential for the inter-subject comparison and longitudinal monitoring of absolute BFI in a variety of tissues/organs with different volumes/geometries.« less

Diffuse optical monitoring of peripheral tissues during uncontrolled internal hemorrhage in a porcine model

PubMed Central

Vishwanath, Karthik; Gurjar, Rajan; Wolf, David; Riccardi, Suzannah; Duggan, Michael; King, David

2018-01-01

Reliable, continuous and noninvasive blood flow and hemoglobin monitoring in trauma patients remains a critical, but generally unachieved goal. Two optical sensing methods - diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) – are used to monitor and detect internal hemorrhage. Specifically, we investigate if cutaneous perfusion measurements acquired using DCS and DRS in peripheral (thighs and ear-lobe) tissues could detect severe hemorrhagic shock in a porcine model. Four animals underwent high-grade hepato-portal injury in a closed abdomen, to induce uncontrolled hemorrhage and were subsequently allowed to bleed for 10 minutes before fluid resuscitation. DRS and DCS measurements of cutaneous blood flow were acquired using fiber optical probes placed on the thigh and earlobe of the animals and were obtained repeatedly starting from 1 to 5 minutes pre-injury, up to several minutes post shock. Clear changes were observed in measured optical spectra across all animals at both sites. DCS-derived cutaneous blood flow decreased sharply during hemorrhage, while DRS-derived vascular saturation and hemoglobin paralleled cardiac output. All derived optical parameters had the steepest changes during the rapid initial hemorrhage unambiguously. This suggests that a combined DCS and DRS based device might provide an easy-to-use, non-invasive, internal-hemorrhage detection system that can be used across a wide array of clinical settings. PMID:29552394

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

Evaluation of blood flow in human exercising muscle by diffuse correlation spectroscopy: a phantom model study

NASA Astrophysics Data System (ADS)

Nakabayashi, Mikie; Ono, Yumie; Ichinose, Masashi

2018-02-01

Diffuse correlation spectroscopy (DCS) has a potential to noninvasively and quantitatively measure the blood flow in the exercising muscle that could contribute to the fields of sports physiology and medicine. However, the blood flow index (BFI) measured from skin surface by DCS reflects hemodynamic signals from both superficial tissue and muscle layer. Thus, an appropriate calibration technology is required to quantify the absolute blood flow in the muscle layer. We therefore fabricated a realistic two-layer phantom model consisted of a static silicon layer imitating superficial tissue and a dynamic flow layer imitating the muscle blood flow and investigated the relationship between the simulated blood flow rate in the muscle layer and the BFI measured from the surface of the phantom. The absorption coefficient and the reduced scattering coefficient of the forearm were measured from 25 healthy young adults using a time-resolved nearinfrared spectroscopy. The depths of the superficial and muscle layers of forearm were also determined by ultrasound tomography images from 25 healthy young adults. The phantoms were fabricated to satisfy these optical coefficients and anatomical constraints. The simulated blood flow rate were set from 0 mL/ min to 68.7 mL/ min in ten steps, which is considered to cover a physiological range of mean blood flow of the forearm between per 100g of muscle tissue at rest to heavy dynamic handgrip exercise. We found a proportional relationship between the flow rates and BFIs with significant correlation coefficient of R = 0.986. Our results suggest that the absolute exercising muscle blood flow could be estimated by DCS with optimal calibration using phantom models.

Dual-comb spectroscopy of molecular electronic transitions in condensed phases

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

A fiber optic probe coupled low-cost CMOS-camera-based system for simultaneous measurement of oxy-, deoxyhemoglobin, and blood flow

NASA Astrophysics Data System (ADS)

Seong, Myeongsu; Phillips, Zephaniah; Mai, Phuong M.; Yeo, Chaebeom; Song, Cheol; Lee, Kijoon; Kim, Jae G.

2015-07-01

Appropriate oxygen supply and blood flow are important in coordination of body functions and maintaining a life. To measure both oxygen supply and blood flow simultaneously, we developed a system that combined near-infrared spectroscopy (NIRS) and diffuse speckle contrast analysis (DSCA). Our system is more cost effective and compact than such combined systems as diffuse correlation spectroscopy(DCS)-NIRS or DCS flow oximeter, and also offers the same quantitative information. In this article, we present the configuration of DSCA-NIRS and preliminary data from an arm cuff occlusion and a repeated gripping exercise. With further investigation, we believe that DSCA-NIRS can be a useful tool for the field of neuroscience, muscle physiology and metabolic diseases such as diabetes.

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

PubMed

Guhathakurta, Debarpan; Dutta, Anirban

2016-01-01

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

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

PubMed Central

Guhathakurta, Debarpan; Dutta, Anirban

2016-01-01

Transcranial direct current stimulation (tDCS) modulates cortical neural activity and hemodynamics. Electrophysiological methods (electroencephalography-EEG) measure neural activity while optical methods (near-infrared spectroscopy-NIRS) measure hemodynamics coupled through neurovascular coupling (NVC). Assessment of NVC requires development of NIRS-EEG joint-imaging sensor montages that are sensitive to the tDCS affected brain areas. In this methods paper, we present a software pipeline incorporating freely available software tools that can be used to target vascular territories with tDCS and develop a NIRS-EEG probe for joint imaging of tDCS-evoked responses. We apply this software pipeline to target primarily the outer convexity of the brain territory (superficial divisions) of the middle cerebral artery (MCA). We then present a computational method based on Empirical Mode Decomposition of NIRS and EEG time series into a set of intrinsic mode functions (IMFs), and then perform a cross-correlation analysis on those IMFs from NIRS and EEG signals to model NVC at the lesional and contralesional hemispheres of an ischemic stroke patient. For the contralesional hemisphere, a strong positive correlation between IMFs of regional cerebral hemoglobin oxygen saturation and the log-transformed mean-power time-series of IMFs for EEG with a lag of about −15 s was found after a cumulative 550 s stimulation of anodal tDCS. It is postulated that system identification, for example using a continuous-time autoregressive model, of this coupling relation under tDCS perturbation may provide spatiotemporal discriminatory features for the identification of ischemia. Furthermore, portable NIRS-EEG joint imaging can be incorporated into brain computer interfaces to monitor tDCS-facilitated neurointervention as well as cortical reorganization. PMID:27378836

Quantifying the cerebral metabolic rate of oxygen by combining diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy.

PubMed

Verdecchia, Kyle; Diop, Mamadou; Lee, Ting-Yim; St Lawrence, Keith

2013-02-01

Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen (CMRO2) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute CMRO2 could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation (SvO2) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, CMRO2 was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of SvO2 measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding CMRO2 measurements. Bland-Altman analysis showed a mean CMRO2 difference of 0.0268 ± 0.8340 mLO2/100 g/min between the two techniques over a range from 0.3 to 4 mL O2/100 g/min.

Quantifying the cerebral metabolic rate of oxygen by combining diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Verdecchia, Kyle; Diop, Mamadou; Lee, Ting-Yim; St. Lawrence, Keith

2013-02-01

Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen (CMRO2) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute CMRO2 could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation (SvO2) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, CMRO2 was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of SvO2 measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding CMRO2 measurements. Bland-Altman analysis showed a mean CMRO2 difference of 0.0268±0.8340 mL O2/100 g/min between the two techniques over a range from 0.3 to 4 mL O2/100 g/min.

Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation.

PubMed

Muthalib, Makii; Besson, Pierre; Rothwell, John; Perrey, Stéphane

2017-07-17

High-definition transcranial direct current stimulation (HD-tDCS) using a 4 × 1 electrode montage has been previously shown using modeling and physiological studies to constrain the electric field within the spatial extent of the electrodes. The aim of this proof-of-concept study was to determine if functional near-infrared spectroscopy (fNIRS) neuroimaging can be used to determine a hemodynamic correlate of this 4 × 1 HD-tDCS electric field on the brain. In a three session cross-over study design, 13 healthy males received one sham (2 mA, 30 sec) and two real (HD-tDCS-1 and HD-tDCS-2, 2 mA, 10 min) anodal HD-tDCS targeting the left M1 via a 4 × 1 electrode montage (anode on C3 and 4 return electrodes 3.5 cm from anode). The two real HD-tDCS sessions afforded a within-subject replication of the findings. fNIRS was used to measure changes in brain hemodynamics (oxygenated hemoglobin integral-O 2 Hb int ) during each 10 min session from two regions of interest (ROIs) in the stimulated left hemisphere that corresponded to "within" (L in ) and "outside" (L out ) the spatial extent of the 4 × 1 electrode montage, and two corresponding ROIs (R in and R out ) in the right hemisphere. The ANOVA showed that both real anodal HD-tDCS compared to sham induced a significantly greater O 2 Hb int in the L in than L out ROIs of the stimulated left hemisphere; while there were no significant differences between the real and sham sessions for the right hemisphere ROIs. Intra-class correlation coefficients showed "fair-to-good" reproducibility for the left stimulated hemisphere ROIs. The greater O 2 Hb int "within" than "outside" the spatial extent of the 4 × 1 electrode montage represents a hemodynamic correlate of the electrical field distribution, and thus provides a prospective reliable method to determine the dose of stimulation that is necessary to optimize HD-tDCS parameters in various applications. © 2017 International Neuromodulation Society.

Pressure injury prediction using diffusely scattered light

NASA Astrophysics Data System (ADS)

Diaz, David; Lafontant, Alec; Neidrauer, Michael; Weingarten, Michael S.; DiMaria-Ghalili, Rose Ann; Scruggs, Ericka; Rece, Julianne; Fried, Guy W.; Kuzmin, Vladimir L.; Zubkov, Leonid

2017-02-01

Pressure injuries (PIs) originate beneath the surface of the skin at the interface between bone and soft tissue. We used diffuse correlation spectroscopy (DCS) and diffuse near-infrared spectroscopy (DNIRS) to predict the development of PIs by measuring dermal and subcutaneous red cell motion and optical absorption and scattering properties in 11 spinal cord injury subjects with only nonbleachable redness in the sacrococcygeal area in a rehabilitation hospital and 20 healthy volunteers. A custom optical probe was developed to obtain continuous DCS and DNIRS data from sacrococcygeal tissue while the subjects were placed in supine and lateral positions to apply pressure from body weight and to release pressure, respectively. Rehabilitation patients were measured up to four times over a two-week period. Three rehabilitation patients developed open PIs (POs) within four weeks and eight patients did not (PNOs). Temporal correlation functions in the area of redness were significantly different (p<0.01) during both baseline and applied pressure stages for POs and PNOs. The results show that our optical method may be used for the early prediction of ulcer progression.

In Vivo, Non-Invasive Characterization of Human Bone by Hybrid Broadband (600-1200 nm) Diffuse Optical and Correlation Spectroscopies.

PubMed

Konugolu Venkata Sekar, Sanathana; Pagliazzi, Marco; Negredo, Eugènia; Martelli, Fabrizio; Farina, Andrea; Dalla Mora, Alberto; Lindner, Claus; Farzam, Parisa; Pérez-Álvarez, Núria; Puig, Jordi; Taroni, Paola; Pifferi, Antonio; Durduran, Turgut

2016-01-01

Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600-1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care.

In Vivo, Non-Invasive Characterization of Human Bone by Hybrid Broadband (600-1200 nm) Diffuse Optical and Correlation Spectroscopies

PubMed Central

Pagliazzi, Marco; Negredo, Eugènia; Martelli, Fabrizio; Farina, Andrea; Dalla Mora, Alberto; Lindner, Claus; Farzam, Parisa; Pérez-Álvarez, Núria; Puig, Jordi; Taroni, Paola; Pifferi, Antonio; Durduran, Turgut

2016-01-01

Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600–1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care. PMID:27997565

Sensing vascularization of ex-vivo produced oral mucosal equivalent (EVPOME) skin grafts in nude mice using optical spectroscopy

NASA Astrophysics Data System (ADS)

Vishwanath, Karthik; Gurjar, Rajan; Kuo, Shiuhyang; Fasi, Anthony; Kim, Roderick; Riccardi, Suzannah; Feinberg, Stephen E.; Wolf, David E.

2014-03-01

Repair of soft tissue defects of the lips as seen in complex maxillofacial injuries, requires pre-vascularized multi-tissue composite grafts. Protocols for fabrication of human ex-vivo produced oral mucosal equivalents (EVPOME) composed of epithelial cells and a dermal equivalent are available to create prelaminated flaps for grafting in patients. However, invivo assessment of neovascularization of the buried prelaminated flaps remains clinically challenging. Here, we use diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to non-invasively quantify longitudinal changes in the vessel density and blood-flow within EVPOME grafts implanted in the backs of SCID mice and subsequently to determine the utility of these optical techniques for assessing vascularization of implanted grafts. 20 animals were implanted with EVPOME grafts (1x1x0.05 cm3) in their backs. DRS and DCS measurements were obtained from each animal both atop the graft site and far away from the graft site, at one week post-implantation, each week, for four consecutive weeks. DRS spectra were analyzed using an inverse Monte Carlo model to extract tissue absorption and scattering coefficients, which were then used to extract blood flow information by fitting the experimental DCS traces. There were clear differences in the mean optical parameters (averaged across all mice) at the graft site vs. the off-site measurements. Both the total hemoglobin concentration (from DRS) and the relative blood flow (from DCS) peaked at week 3 at the graft site and declined to the off-site values by week 4. The optical parameters remained relatively constant throughout 4 weeks for the off-site measurements.

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

NASA Astrophysics Data System (ADS)

Scagline, Steffany M.

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

NIRS-EEG joint imaging during transcranial direct current stimulation: Online parameter estimation with an autoregressive model.

PubMed

Sood, Mehak; Besson, Pierre; Muthalib, Makii; Jindal, Utkarsh; Perrey, Stephane; Dutta, Anirban; Hayashibe, Mitsuhiro

2016-12-01

Transcranial direct current stimulation (tDCS) has been shown to perturb both cortical neural activity and hemodynamics during (online) and after the stimulation, however mechanisms of these tDCS-induced online and after-effects are not known. Here, online resting-state spontaneous brain activation may be relevant to monitor tDCS neuromodulatory effects that can be measured using electroencephalography (EEG) in conjunction with near-infrared spectroscopy (NIRS). We present a Kalman Filter based online parameter estimation of an autoregressive (ARX) model to track the transient coupling relation between the changes in EEG power spectrum and NIRS signals during anodal tDCS (2mA, 10min) using a 4×1 ring high-definition montage. Our online ARX parameter estimation technique using the cross-correlation between log (base-10) transformed EEG band-power (0.5-11.25Hz) and NIRS oxy-hemoglobin signal in the low frequency (≤0.1Hz) range was shown in 5 healthy subjects to be sensitive to detect transient EEG-NIRS coupling changes in resting-state spontaneous brain activation during anodal tDCS. Conventional sliding window cross-correlation calculations suffer a fundamental problem in computing the phase relationship as the signal in the window is considered time-invariant and the choice of the window length and step size are subjective. Here, Kalman Filter based method allowed online ARX parameter estimation using time-varying signals that could capture transients in the coupling relationship between EEG and NIRS signals. Our new online ARX model based tracking method allows continuous assessment of the transient coupling between the electrophysiological (EEG) and the hemodynamic (NIRS) signals representing resting-state spontaneous brain activation during anodal tDCS. Published by Elsevier B.V.

Interferometric Near-Infrared Spectroscopy (iNIRS) for determination of optical and dynamical properties of turbid media

PubMed Central

Borycki, Dawid; Kholiqov, Oybek; Chong, Shau Poh; Srinivasan, Vivek J.

2016-01-01

We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts optical and dynamical properties of turbid media through analysis of a spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency-swept narrow linewidth laser. Fourier analysis of the detected signal is used to determine time-of-flight (TOF)-resolved intensity, which is then analyzed over time to yield TOF-resolved intensity autocorrelations. This approach enables quantification of optical properties, which is not possible in conventional, continuous-wave near-infrared spectroscopy (NIRS). Furthermore, iNIRS quantifies scatterer motion based on TOF-resolved autocorrelations, which is a feature inaccessible by well-established diffuse correlation spectroscopy (DCS) techniques. We prove this by determining TOF-resolved intensity and temporal autocorrelations for light transmitted through diffusive fluid phantoms with optical thicknesses of up to 55 reduced mean free paths (approximately 120 scattering events). The TOF-resolved intensity is used to determine optical properties with time-resolved diffusion theory, while the TOF-resolved intensity autocorrelations are used to determine dynamics with diffusing wave spectroscopy. iNIRS advances the capabilities of diffuse optical methods and is suitable for in vivo tissue characterization. Moreover, iNIRS combines NIRS and DCS capabilities into a single modality. PMID:26832264

Use of functional near-infrared spectroscopy to evaluate the effects of anodal transcranial direct current stimulation on brain connectivity in motor-related cortex

NASA Astrophysics Data System (ADS)

Yan, Jiaqing; Wei, Yun; Wang, Yinghua; Xu, Gang; Li, Zheng; Li, Xiaoli

2015-04-01

Transcranial direct current stimulation (tDCS) is a noninvasive, safe and convenient neuro-modulatory technique in neurological rehabilitation, treatment, and other aspects of brain disorders. However, evaluating the effects of tDCS is still difficult. We aimed to evaluate the effects of tDCS using hemodynamic changes using functional near-infrared spectroscopy (fNIRS). Five healthy participants were employed and anodal tDCS was applied to the left motor-related cortex, with cathodes positioned on the right dorsolateral supraorbital area. fNIRS data were collected from the right motor-related area at the same time. Functional connectivity (FC) between intracortical regions was calculated between fNIRS channels using a minimum variance distortion-less response magnitude squared coherence (MVDR-MSC) method. The levels of Oxy-HbO change and the FC between channels during the prestimulation, stimulation, and poststimulation stages were compared. Results showed no significant level difference, but the FC measured by MVDR-MSC significantly decreased during tDCS compared with pre-tDCS and post-tDCS, although the FC difference between pre-tDCS and post-tDCS was not significant. We conclude that coherence calculated from resting state fNIRS may be a useful tool for evaluating the effects of anodal tDCS and optimizing parameters for tDCS application.

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

PubMed Central

McKendrick, Ryan; Parasuraman, Raja; Ayaz, Hasan

2015-01-01

Contemporary studies with transcranial direct current stimulation (tDCS) provide a growing base of evidence for enhancing cognition through the non-invasive delivery of weak electric currents to the brain. The main effect of tDCS is to modulate cortical excitability depending on the polarity of the applied current. However, the underlying mechanism of neuromodulation is not well understood. A new generation of functional near infrared spectroscopy (fNIRS) systems is described that are miniaturized, portable, and include wearable sensors. These developments provide an opportunity to couple fNIRS with tDCS, consistent with a neuroergonomics approach for joint neuroimaging and neurostimulation investigations of cognition in complex tasks and in naturalistic conditions. The effects of tDCS on complex task performance and the use of fNIRS for monitoring cognitive workload during task performance are described. Also explained is how fNIRS + tDCS can be used simultaneously for assessing spatial working memory. Mobile optical brain imaging is a promising neuroimaging tool that has the potential to complement tDCS for realistic applications in natural settings. PMID:25805976

Diffuse Optics for Tissue Monitoring and Tomography

PubMed Central

Durduran, T; Choe, R; Baker, W B; Yodh, A G

2015-01-01

This review describes the diffusion model for light transport in tissues and the medical applications of diffuse light. Diffuse optics is particularly useful for measurement of tissue hemodynamics, wherein quantitative assessment of oxy- and deoxy-hemoglobin concentrations and blood flow are desired. The theoretical basis for near-infrared or diffuse optical spectroscopy (NIRS or DOS, respectively) is developed, and the basic elements of diffuse optical tomography (DOT) are outlined. We also discuss diffuse correlation spectroscopy (DCS), a technique whereby temporal correlation functions of diffusing light are transported through tissue and are used to measure blood flow. Essential instrumentation is described, and representative brain and breast functional imaging and monitoring results illustrate the workings of these new tissue diagnostics. PMID:26120204

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

PubMed Central

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

2014-01-01

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

Optical measurement of blood flow in exercising skeletal muscle: a pilot study

NASA Astrophysics Data System (ADS)

Wang, Detian; Baker, Wesley B.; Parthasarathy, Ashwin B.; Zhu, Liguo; Li, Zeren; Yodh, Arjun G.

2017-07-01

Blood flow monitoring during rhythm exercising is very important for sports medicine and muscle dieases. Diffuse correlation spectroscopy(DCS) is a relative new invasive way to monitor blood flow but suffering from muscle fiber motion. In this study we focus on how to remove exercise driven artifacts and obtain accurate estimates of the increase in blood flow from exercise. Using a novel fast software correlator, we measured blood flow in forearm flexor muscles of N=2 healthy adults during handgrip exercise, at a sampling rate of 20 Hz. Combining the blood flow and acceleration data, we resolved the motion artifact in the DCS signal induced by muscle fiber motion, and isolated the blood flow component of the signal from the motion artifact. The results show that muscle fiber motion strongly affects the DCS signal, and if not accounted for, will result in an overestimate of blood flow more than 1000%. Our measurements indicate rapid dilation of arterioles following exercise onset, which enabled blood flow to increase to a plateau of 200% in 10s. The blood flow also rapidly recovered to baseline following exercise in 10s. Finally, preliminary results on the dependence of blood flow from exercise intensity changes will be discussed.

Assessment of sacrococcygeal pressure ulcers using diffuse correlation spectroscopy

NASA Astrophysics Data System (ADS)

Diaz, David; Lafontant, Alec; Neidrauer, Michael; Weingarten, Michael S.; DiMaria-Ghalili, Rose Ann; Fried, Guy W.; Rece, Julianne; Lewin, Peter A.; Zubkov, Leonid

2016-03-01

Microcirculation is essential for proper supply of oxygen and nutritive substances to the biological tissue and the removal of waste products of metabolism. The determination of microcirculatory blood flow (mBF) is therefore of substantial interest to clinicians for assessing tissue health; particularly in pressure ulceration and suspected deep tissue injury. The goal of this pilot clinical study was to assess deep-tissue pressure ulceration by non-invasively measuring mBF using Diffuse Correlation Spectroscopy (DCS). DCS provides information about the flow of red blood cells in the capillary network by measuring the temporal autocorrelation function of scattering light intensity. A novel optical probe was developed in order to obtain measurements under the load of the subject's body as pressure is applied (ischemia) and then released (reperfusion) on sacrococcygeal tissue in a hospital bed. Prior to loading measurements, baseline readings of the sacral region were obtained by measuring the subjects in a side-lying position. DCS measurements from the sacral region of twenty healthy volunteers have been compared to those of two patients who initially had similar non-blanchable redness. The temporal autocorrelation function of scattering light intensity of the patient whose redness later disappeared was similar to that of the average healthy subject. The second patient, whose redness developed into an advanced pressure ulcer two weeks later, had a substantial decrease in blood flow while under the loading position compared to healthy subjects. Preliminary results suggest the developed system may potentially predict whether non-blanchable redness will manifest itself as advanced ulceration or dissipate over time.

Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology

PubMed Central

Dehaes, Mathieu; Cheng, Henry H.; Buckley, Erin M.; Lin, Pei-Yi; Ferradal, Silvina; Williams, Kathryn; Vyas, Rutvi; Hagan, Katherine; Wigmore, Daniel; McDavitt, Erica; Soul, Janet S.; Franceschini, Maria Angela; Newburger, Jane W.; Ellen Grant, P.

2015-01-01

Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi), cerebral oxygen metabolism (CMRO2i) and SO2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO2i and CBFi, which returned to baseline when stable. However, SO2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO2 alone. PMID:26713191

Adaptive sampling dual terahertz comb spectroscopy using dual free-running femtosecond lasers.

PubMed

Yasui, Takeshi; Ichikawa, Ryuji; Hsieh, Yi-Da; Hayashi, Kenta; Cahyadi, Harsono; Hindle, Francis; Sakaguchi, Yoshiyuki; Iwata, Tetsuo; Mizutani, Yasuhiro; Yamamoto, Hirotsugu; Minoshima, Kaoru; Inaba, Hajime

2015-06-02

Terahertz (THz) dual comb spectroscopy (DCS) is a promising method for high-accuracy, high-resolution, broadband THz spectroscopy because the mode-resolved THz comb spectrum includes both broadband THz radiation and narrow-line CW-THz radiation characteristics. In addition, all frequency modes of a THz comb can be phase-locked to a microwave frequency standard, providing excellent traceability. However, the need for stabilization of dual femtosecond lasers has often hindered its wide use. To overcome this limitation, here we have demonstrated adaptive-sampling THz-DCS, allowing the use of free-running femtosecond lasers. To correct the fluctuation of the time and frequency scales caused by the laser timing jitter, an adaptive sampling clock is generated by dual THz-comb-referenced spectrum analysers and is used for a timing clock signal in a data acquisition board. The results not only indicated the successful implementation of THz-DCS with free-running lasers but also showed that this configuration outperforms standard THz-DCS with stabilized lasers due to the slight jitter remained in the stabilized lasers.

Adaptive sampling dual terahertz comb spectroscopy using dual free-running femtosecond lasers

PubMed Central

Yasui, Takeshi; Ichikawa, Ryuji; Hsieh, Yi-Da; Hayashi, Kenta; Cahyadi, Harsono; Hindle, Francis; Sakaguchi, Yoshiyuki; Iwata, Tetsuo; Mizutani, Yasuhiro; Yamamoto, Hirotsugu; Minoshima, Kaoru; Inaba, Hajime

2015-01-01

Terahertz (THz) dual comb spectroscopy (DCS) is a promising method for high-accuracy, high-resolution, broadband THz spectroscopy because the mode-resolved THz comb spectrum includes both broadband THz radiation and narrow-line CW-THz radiation characteristics. In addition, all frequency modes of a THz comb can be phase-locked to a microwave frequency standard, providing excellent traceability. However, the need for stabilization of dual femtosecond lasers has often hindered its wide use. To overcome this limitation, here we have demonstrated adaptive-sampling THz-DCS, allowing the use of free-running femtosecond lasers. To correct the fluctuation of the time and frequency scales caused by the laser timing jitter, an adaptive sampling clock is generated by dual THz-comb-referenced spectrum analysers and is used for a timing clock signal in a data acquisition board. The results not only indicated the successful implementation of THz-DCS with free-running lasers but also showed that this configuration outperforms standard THz-DCS with stabilized lasers due to the slight jitter remained in the stabilized lasers. PMID:26035687

Investigations of the functional states of dendritic cells under different conditioned microenvironments by Fourier transformed infrared spectroscopy.

PubMed

Dong, Rong; Long, Jinhua; Xu, Xiaoli; Zhang, Chunlin; Wen, Zongyao; Li, Long; Yao, Weijuan; Zeng, Zhu

2014-01-10

Dendritic cells are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. The dendritic cell-based vaccination against cancer has been clinically achieved promising successes. But there are still many challenges in its clinical application, especially for how to identify the functional states. The CD14+ monocytes were isolated from human peripheral blood after plastic adherence and purified to approximately 98% with cocktail immunomagnetic beads. The immature dendritic cells and mature dendritic cells were induced by traditional protocols. The resulting dendritic cells were cocultured with normal cells and cancer cells. The functional state of dendritic cells including immature dendritic cells (imDCs) and mature dendritic cells (mDCs) under different conditioned microenvironments were investigated by Fourier transformed infrared spectroscopy (FTIR) and molecular biological methods. The results of Fourier transformed infrared spectroscopy showed that the gene transcription activity and energy states of dendritic cells were specifically suppressed by tumor cells (P < 0.05 or 0.01). The expression levels of NF-kappa B (NF-κB) in dendritic cells were also specifically inhibited by tumor-derived factors (P < 0.05 or 0.01). Moreover, the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were closely correlated with the expression levels of NF-κB (R2:0.69 and R2:0.81, respectively). Our results confirmed that the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were positively correlated with the expression levels of NF-κB, suggesting that Fourier transformed infrared spectroscopy technology could be clinically applied to identify the functional states of dendritic cell when performing dendritic cell-based vaccination. It's significant for the simplification and standardization of dendritic cell-based vaccination clinical preparation protocols.

Use of functional near-infrared spectroscopy to monitor cortical plasticity induced by transcranial direct current stimulation

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hervey, Nathan; Stowe, Ann; Hodics, Timea; Alexandrakis, George

2013-03-01

Electrical stimulation of the human cortex in conjunction with physical rehabilitation has been a valuable approach in facilitating the plasticity of the injured brain. One such method is transcranial direct current stimulation (tDCS) which is a non-invasive method to elicit neural stimulation by delivering current through electrodes placed on the scalp. In order to better understand the effects tDCS has on cortical plasticity, neuroimaging techniques have been used pre and post tDCS stimulation. Recently, neuroimaging methods have discovered changes in resting state cortical hemodynamics after the application of tDCS on human subjects. However, analysis of the cortical hemodynamic activity for a physical task during and post tDCS stimulation has not been studied to our knowledge. A viable and sensitive neuroimaging method to map changes in cortical hemodynamics during activation is functional near-infrared spectroscopy (fNIRS). In this study, the cortical activity during an event-related, left wrist curl task was mapped with fNIRS before, during, and after tDCS stimulation on eight healthy adults. Along with the fNIRS optodes, two electrodes were placed over the sensorimotor hand areas of both brain hemispheres to apply tDCS. Changes were found in both resting state cortical connectivity and cortical activation patterns that occurred during and after tDCS. Additionally, changes to surface electromyography (sEMG) measurements of the wrist flexor and extensor of both arms during the wrist curl movement, acquired concurrently with fNIRS, were analyzed and related to the transient cortical plastic changes induced by tDCS.

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.

Repetitive Transcranial Direct Current Stimulation Induced Excitability Changes of Primary Visual Cortex and Visual Learning Effects-A Pilot Study.

PubMed

Sczesny-Kaiser, Matthias; Beckhaus, Katharina; Dinse, Hubert R; Schwenkreis, Peter; Tegenthoff, Martin; Höffken, Oliver

2016-01-01

Studies on noninvasive motor cortex stimulation and motor learning demonstrated cortical excitability as a marker for a learning effect. Transcranial direct current stimulation (tDCS) is a non-invasive tool to modulate cortical excitability. It is as yet unknown how tDCS-induced excitability changes and perceptual learning in visual cortex correlate. Our study aimed to examine the influence of tDCS on visual perceptual learning in healthy humans. Additionally, we measured excitability in primary visual cortex (V1). We hypothesized that anodal tDCS would improve and cathodal tDCS would have minor or no effects on visual learning. Anodal, cathodal or sham tDCS were applied over V1 in a randomized, double-blinded design over four consecutive days (n = 30). During 20 min of tDCS, subjects had to learn a visual orientation-discrimination task (ODT). Excitability parameters were measured by analyzing paired-stimulation behavior of visual-evoked potentials (ps-VEP) and by measuring phosphene thresholds (PTs) before and after the stimulation period of 4 days. Compared with sham-tDCS, anodal tDCS led to an improvement of visual discrimination learning (p < 0.003). We found reduced PTs and increased ps-VEP ratios indicating increased cortical excitability after anodal tDCS (PT: p = 0.002, ps-VEP: p = 0.003). Correlation analysis within the anodal tDCS group revealed no significant correlation between PTs and learning effect. For cathodal tDCS, no significant effects on learning or on excitability could be seen. Our results showed that anodal tDCS over V1 resulted in improved visual perceptual learning and increased cortical excitability. tDCS is a promising tool to alter V1 excitability and, hence, perceptual visual learning.

Development of Point of Care Testing Device for Neurovascular Coupling From Simultaneous Recording of EEG and NIRS During Anodal Transcranial Direct Current Stimulation

PubMed Central

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

2015-01-01

This paper presents a point of care testing device for neurovascular coupling (NVC) from simultaneous recording of electroencephalogram (EEG) and near infrared spectroscopy (NIRS) during anodal transcranial direct current stimulation (tDCS). Here, anodal tDCS modulated cortical neural activity leading to hemodynamic response can be used to identify the impaired cerebral microvessels functionality. The impairments in the cerebral microvessels functionality may lead to impairments in the cerebrovascular reactivity (CVR), where severely reduced CVR predicts the chances of transient ischemic attack and ipsilateral stroke. The neural and hemodynamic responses to anodal tDCS were studied through joint imaging with EEG and NIRS, where NIRS provided optical measurement of changes in tissue oxy-(\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$HbO2)$ \\end{document} and deoxy-(\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$Hb$ \\end{document}) hemoglobin concentration and EEG captured alterations in the underlying neuronal current generators. Then, a cross-correlation method for the assessment of NVC underlying the site of anodal tDCS is presented. The feasibility studies on healthy subjects and stroke survivors showed detectable changes in the EEG and the NIRS responses to a 0.526 A/\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\mathrm{m}^{2}$ \\end{document} of anodal tDCS. The NIRS system was bench tested on 15 healthy subjects that showed a statistically significant (p < 0.01) difference in the signal-to-noise ratio (SNR) between the ON- and OFF-states of anodal tDCS where the mean SNR of the NIRS device was found to be 42.33 ± 1.33 dB in the ON-state and 40.67 ± 1.23 dB in the OFF-state. Moreover, the clinical study conducted on 14 stroke survivors revealed that the lesioned hemisphere with impaired circulation showed significantly (p < 0.01) less change in \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$HbO2$ \\end{document} than the nonlesioned side in response to anodal tDCS. The EEG study on healthy subjects showed a statistically significant (p < 0.05) decrease around individual alpha frequency in the alpha band (8−13 Hz) following anodal tDCS. Moreover, the joint EEG-NIRS imaging on 4 stroke survivors showed an immediate increase in the theta band (4−8 Hz) EEG activity after the start of anodal tDCS at the nonlesioned hemisphere. Furthermore, cross-correlation function revealed a significant (95% confidence interval) negative cross correlation only at the nonlesioned hemisphere during anodal tDCS, where the log-transformed mean-power of EEG within 0.5−11.25 Hz lagged \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$HbO2$ \\end{document} response in one of the stroke survivors with white matter lesions. Therefore, it was concluded that the anodal tDCS can perturb the local neural and the vascular activity (via NVC) which can be used for assessing regional NVC functionality where confirmatory clinical studies are required. PMID:27170897

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.

Compact dual-mode diffuse optical system for blood perfusion monitoring in a porcine model of microvascular tissue flaps

NASA Astrophysics Data System (ADS)

Lee, Seung Yup; Pakela, Julia M.; Helton, Michael C.; Vishwanath, Karthik; Chung, Yooree G.; Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Christian, James F.; O'Reilly, Jameson; Farkas, Dana; Ward, Brent B.; Feinberg, Stephen E.; Mycek, Mary-Ann

2017-12-01

In reconstructive surgery, the ability to detect blood flow interruptions to grafted tissue represents a critical step in preventing postsurgical complications. We have developed and pilot tested a compact, fiber-based device that combines two complimentary modalities-diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy-to quantitatively monitor blood perfusion. We present a proof-of-concept study on an in vivo porcine model (n=8). With a controllable arterial blood flow supply, occlusion studies (n=4) were performed on surgically isolated free flaps while the device simultaneously monitored blood flow through the supplying artery as well as flap perfusion from three orientations: the distal side of the flap and two transdermal channels. Further studies featuring long-term monitoring, arterial failure simulations, and venous failure simulations were performed on flaps that had undergone an anastomosis procedure (n=4). Additionally, benchtop verification of the DCS system was performed on liquid flow phantoms. Data revealed relationships between diffuse optical measures and state of occlusion as well as the ability to detect arterial and venous compromise. The compact construction of the device, along with its noninvasive and quantitative nature, would make this technology suitable for clinical translation.

Noninvasive optical quantification of absolute blood flow, blood oxygenation, and oxygen consumption rate in exercising skeletal muscle

NASA Astrophysics Data System (ADS)

Gurley, Katelyn; Shang, Yu; Yu, Guoqiang

2012-07-01

This study investigates a method using novel hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] to obtain continuous, noninvasive measurement of absolute blood flow (BF), blood oxygenation, and oxygen consumption rate (\\Vdot O2) in exercising skeletal muscle. Healthy subjects (n=9) performed a handgrip exercise to increase BF and \\Vdot O2 in forearm flexor muscles, while a hybrid optical probe on the skin surface directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO2], [Hb], and THC), tissue oxygen saturation (StO2), relative BF (rBF), and relative oxygen consumption rate (r\\Vdot O2). The rBF and r\\Vdot O2 signals were calibrated with absolute baseline BF and \\Vdot O2 obtained through venous and arterial occlusions, respectively. Known problems with muscle-fiber motion artifacts in optical measurements during exercise were mitigated using a novel gating algorithm that determined muscle contraction status based on control signals from a dynamometer. Results were consistent with previous findings in the literature. This study supports the application of NIRS/DCS technology to quantitatively evaluate hemodynamic and metabolic parameters in exercising skeletal muscle and holds promise for improving diagnosis and treatment evaluation for patients suffering from diseases affecting skeletal muscle and advancing fundamental understanding of muscle and exercise physiology.

Fiber-based hybrid probe for non-invasive cerebral monitoring in neonatology

NASA Astrophysics Data System (ADS)

Rehberger, Matthias; Giovannella, Martina; Pagliazzi, Marco; Weigel, Udo; Durduran, Turgut; Contini, Davide; Spinelli, Lorenzo; Pifferi, Antonio; Torricelli, Alessandro; Schmitt, Robert

2015-07-01

Improved cerebral monitoring systems are needed to prevent preterm infants from long-term cognitive and motor restrictions. Combining advanced near-infrared diffuse spectroscopy measurement technologies, time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) will introduce novel indicators of cerebral oxygen metabolism and blood flow for neonatology. For non-invasive sensing a fiber-optical probe is used to send and receive light from the infant head. In this study we introduce a new fiber-based hybrid probe that is designed for volume production. The probe supports TRS and DCS measurements in a cross geometry, thus both technologies gain information on the same region inside the tissue. The probe is highly miniaturized to perform cerebral measurements on heads of extreme preterm infants down to head diameters of 6cm. Considerations concerning probe production focus on a reproducible accuracy in shape and precise optical alignment. In this way deviations in measurement data within a series of probes should be minimized. In addition to that, requirements for clinical use like robustness and hygiene are considered. An additional soft-touching sleeve made of FDA compatible silicone allows for a flexible attachment with respect to the individual anatomy of each patient. We present the technical concept of the hybrid probe and corresponding manufacturing methods. A prototype of the probe is shown and tested on tissue phantoms as well as in vivo to verify its operational reliability.

Noninvasive optical quantification of absolute blood flow, blood oxygenation, and oxygen consumption rate in exercising skeletal muscle

PubMed Central

Gurley, Katelyn; Shang, Yu

2012-01-01

Abstract. This study investigates a method using novel hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] to obtain continuous, noninvasive measurement of absolute blood flow (BF), blood oxygenation, and oxygen consumption rate (V˙O2) in exercising skeletal muscle. Healthy subjects (n=9) performed a handgrip exercise to increase BF and V˙O2 in forearm flexor muscles, while a hybrid optical probe on the skin surface directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO2], [Hb], and THC), tissue oxygen saturation (StO2), relative BF (rBF), and relative oxygen consumption rate (rV˙O2). The rBF and rV˙O2 signals were calibrated with absolute baseline BF and V˙O2 obtained through venous and arterial occlusions, respectively. Known problems with muscle-fiber motion artifacts in optical measurements during exercise were mitigated using a novel gating algorithm that determined muscle contraction status based on control signals from a dynamometer. Results were consistent with previous findings in the literature. This study supports the application of NIRS/DCS technology to quantitatively evaluate hemodynamic and metabolic parameters in exercising skeletal muscle and holds promise for improving diagnosis and treatment evaluation for patients suffering from diseases affecting skeletal muscle and advancing fundamental understanding of muscle and exercise physiology. PMID:22894482

Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

PubMed

Sanborn, Matthew R; Edsell, Mark E; Kim, Meeri N; Mesquita, Rickson; Putt, Mary E; Imray, Chris; Yow, Heng; Wilson, Mark H; Yodh, Arjun G; Grocott, Mike; Martin, Daniel S

2015-06-01

Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

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.

A Nth-order linear algorithm for extracting diffuse correlation spectroscopy blood flow indices in heterogeneous tissues.

PubMed

Shang, Yu; Yu, Guoqiang

2014-09-29

Conventional semi-infinite analytical solutions of correlation diffusion equation may lead to errors when calculating blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements in tissues with irregular geometries. Very recently, we created an algorithm integrating a N th-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in homogenous tissues with arbitrary geometries for extraction of BFI (i.e., αD B ). The purpose of this study is to extend the capability of the N th-order linear algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries. The previous linear algorithm was modified to extract BFIs in different types of tissues simultaneously through utilizing DCS data at multiple source-detector separations. We compared the proposed linear algorithm with the semi-infinite homogenous solution in a computer model of adult head with heterogeneous tissue layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of the linear algorithm for extracting relative changes of cerebral blood flow (rCBF) in deep brain, we assigned ten levels of αD B in the brain layer with a step decrement of 10% while maintaining αD B values constant in other layers. Simulation results demonstrate the accuracy (errors < 3%) of high-order ( N  ≥ 5) linear algorithm in extracting BFIs in different tissue layers and rCBF in deep brain. By contrast, the semi-infinite homogenous solution resulted in substantial errors in rCBF (34.5% ≤ errors ≤ 60.2%) and BFIs in different layers. The N th-order linear model simplifies data analysis, thus allowing for online data processing and displaying. Future study will test this linear algorithm in heterogeneous tissues with different levels of blood flow variations and noises.

Modified Beer-Lambert law for blood flow.

PubMed

Baker, Wesley B; Parthasarathy, Ashwin B; Busch, David R; Mesquita, Rickson C; Greenberg, Joel H; Yodh, A G

2014-11-01

We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues.

Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

NASA Astrophysics Data System (ADS)

Mesquita, Rickson C.; Faseyitan, Olufunsho K.; Turkeltaub, Peter E.; Buckley, Erin M.; Thomas, Amy; Kim, Meeri N.; Durduran, Turgut; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Hamilton, Roy H.

2013-06-01

Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications

PubMed Central

Ferradal, Silvina L.; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G.; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry H.; Newburger, Jane W.; Kaza, Aditya K.; Franceschini, Maria A.; Kussman, Barry D.; Grant, P. Ellen

2017-01-01

The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management. PMID:28276534

Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications.

PubMed

Ferradal, Silvina L; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry H; Newburger, Jane W; Kaza, Aditya K; Franceschini, Maria A; Kussman, Barry D; Grant, P Ellen

2017-03-09

The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO 2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO 2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.

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.

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

PubMed

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

2017-10-19

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

Language Mapping with Navigated Repetitive TMS: Proof of Technique and Validation

PubMed Central

Tarapore, Phiroz E.; Findlay, Anne M.; Honma, Susanne M.; Mizuiri, Danielle; Houde, John F.; Berger, Mitchel S.; Nagarajan, Srikantan S.

2013-01-01

Objective Lesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS. Methods Subjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared. Results nTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects. Conclusion Maps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions. PMID:23702420

Modified Beer-Lambert law for blood flow

PubMed Central

Baker, Wesley B.; Parthasarathy, Ashwin B.; Busch, David R.; Mesquita, Rickson C.; Greenberg, Joel H.; Yodh, A. G.

2014-01-01

We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues. PMID:25426330

A correlation of measles specific antibodies and the number of plasmacytoid dendritic cells is observed after measles vaccination in 9 month old infants

PubMed Central

García-León, Miguel L; Bonifaz, Laura C; Espinosa-Torres, Bogart; Hernández-Pérez, Brenda; Cardiel-Marmolejo, Lino; Santos-Preciado, José I; Wong-Chew, Rosa M

2015-01-01

Measles virus (MeV) represents one of the main causes of death among young children, particularly in developing countries. Upon infection, MeV controls both interferon induction (IFN) and the interferon signaling pathway which results in a severe host immunosuppression that can persists for up to 6 mo after infection. Despite the global biology of MeV infection is well studied, the role of the plasmacytoid dendritic cells (pDCs) during the host innate immune response after measles vaccination remains largely uncharacterized. Here we investigated the role of pDCs, the major producers of interferon in response to viral infections, in the development of adaptive immune response against MeV vaccine. We report that there is a strong correlation between pDCs population and the humoral immune response to Edmonston Zagreb (EZ) measles vaccination in 9-month-old mexican infants. Five infants were further evaluated after vaccination, showing a clear increase in pDCs at baseline, one week and 3 months after immunization. Three months postvaccination they showed increase in memory T-cells and pDCs populations, high induction of adaptive immunity and also observed a correlation between pDCs number and the humoral immune response. These findings suggest that the development and magnitude of the adaptive immune response following measles immunization is directly dependent on the number of pDCs of the innate immune response. PMID:26075901

Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage

NASA Astrophysics Data System (ADS)

Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P. Ellen; Franceschini, Maria Angela

2016-05-01

Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.

The strategy and motivational influences on the beneficial effect of neurostimulation: a tDCS and fNIRS study

PubMed Central

Jones, Kevin T.; Gözenman, Filiz; Berryhill, Marian E.

2014-01-01

Working memory (WM) capacity falls along a spectrum with some people demonstrating higher and others lower WM capacity. Efforts to improve WM include applying transcranial direct current stimulation (tDCS), in which small amounts of current modulate the activity of underlying neurons and enhance cognitive function. However, not everyone benefits equally from a given tDCS protocol. Recent findings revealed tDCS-related WM benefits for individuals with higher working memory (WM) capacity. Here, we test two hypotheses regarding those with low WM capacity to see if they too would benefit under more optimal conditions. We tested whether supplying a WM strategy (Experiment 1) or providing greater extrinsic motivation through incentives (Experiment 2) would restore tDCS benefit to the low WM capacity group. We also employed functional near infrared spectroscopy to monitor tDCS-induced changes in neural activity. Experiment 1 demonstrated that supplying a WM strategy improved the high WM capacity participants’ accuracy and the amount of oxygenated blood levels following anodal tDCS, but it did not restore tDCS-linked WM benefits to the low WM capacity group. Experiment 2 demonstrated that financial motivation enhanced performance in both low and high WM capacity groups, especially after anodal tDCS. Here, only the low WM capacity participants showed a generalized increase in oxygenated blood flow across both low and high motivation conditions. These results indicate that ensuring that participants’ incentives are high may expand cognitive benefits associated with tDCS. This finding is relevant for translational work using tDCS in clinical populations, in which motivation can be a concern. PMID:25462798

The correlation between dental calculus and disturbed mineral metabolism in paediatric patients with chronic kidney disease.

PubMed

Davidovich, Esti; Davidovits, Miriam; Peretz, Benny; Shapira, Joseph; Aframian, Doron J

2009-08-01

Vascular calcifications have been documented in children with end-stage renal disease. However, only a few reports have described abundant dental calculus formation in children suffering from chronic kidney disease (CKD). Moreover, dental calculus scores (DCS) and their correlation with renal disease severity have not been studied. DCS in 74 young CKD patients were evaluated: 25 pre-dialytic (PrD), 18 on dialysis (D) and 31 with transplants (T) compared to 32 healthy participants (C). Saliva and serum analysis included creatinine (Cr), urea (U), calcium (Ca), phosphorous (P), magnesium (Mg) as well as intraoral pH levels. All patient groups presented high DCS. DCS and pH levels were higher in the D group with a positive correlation between pH and lower incisor DCS (r = 0.56, P = 0.017). The highest salivary Ca was found in the PrD group. Salivary P in the PrD group was found to be higher than in the T and C groups. The lowest salivary Mg was found in the D group while the highest salivary Ca x P product was found in the PrD group. In all patient groups, salivary U was higher than in the C group with a 2.5-fold increase in the D group. Salivary Cr resembled the U salivary concentrations. Alterations in salivary Ca, P, Mg, U, Cr and intraoral pH levels were observed in the patient groups. DCS correlated with renal disease severity and therefore may be a reflection of other tissue calcification pathologies found in these patients.

Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities

PubMed Central

Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza e; de Oliveira, Glaucia Maria Moraes

2016-01-01

Background Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. Objective To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Methods Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. Results In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. Conclusion The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions. PMID:27849263

Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities.

PubMed

Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza E; Oliveira, Glaucia Maria Moraes de

2016-10-01

Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions.

Monitoring blood flow and photobleaching during topical ALA PDT treatment

NASA Astrophysics Data System (ADS)

Sands, Theresa L.; Sunar, Ulas; Foster, Thomas H.; Oseroff, Allan R.

2009-02-01

Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) is currently used as a clinical treatment for nonmelanoma skin cancers. In order to optimize PDT treatment, vascular shutdown early in treatment must be identified and prevented. This is especially important for topical ALA PDT where vascular shutdown is only temporary and is not a primary method of cell death. Shutdown in vasculature would limit the delivery of oxygen which is necessary for effective PDT treatment. Diffuse correlation spectroscopy (DCS) was used to monitor relative blood flow changes in Balb/C mice undergoing PDT at fluence rates of 10mW/cm2 and 75mW/cm2 for colon-26 tumors implanted intradermally. DCS is a preferable method to monitor the blood flow during PDT of lesions due to its ability to be used noninvasively throughout treatment, returning data from differing depths of tissue. Photobleaching of the photosensitizer was also monitored during treatment as an indirect manner of monitoring singlet oxygen production. In this paper, we show the conditions that cause vascular shutdown in our tumor model and its effects on the photobleaching rate.

Increased plasmacytoid dendritic cells in Guillain-Barré syndrome.

PubMed

Wang, Yu-Zhong; Feng, Xun-Gang; Wang, Qian; Xing, Chun-Ye; Shi, Qi-Guang; Kong, Qing-Xia; Cheng, Pan-Pan; Zhang, Yong; Hao, Yan-Lei; Yuki, Nobuhiro

2015-06-15

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p<0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-08-01

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

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.

Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

PubMed

Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

2011-01-01

The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Cross-Sectional Analysis of Per Capita Supply of Doctors of Chiropractic and Opioid Use in Younger Medicare Beneficiaries.

PubMed

Weeks, William B; Goertz, Christine M

2016-05-01

The purpose of this study was to determine whether the per-capita supply of doctors of chiropractic (DCs) or Medicare spending on chiropractic care was associated with opioid use among younger, disabled Medicare beneficiaries. Using 2011 data, at the hospital referral region level, we correlated the per-capita supply of DCs and spending on chiropractic manipulative therapy (CMT) with several measures of per-capita opioid use by younger, disabled Medicare beneficiaries. Per-capita supply of DCs and spending on CMT were strongly inversely correlated with the percentage of younger Medicare beneficiaries who had at least 1, as well as with 6 or more, opioid prescription fills. Neither measure was correlated with mean daily morphine equivalents per opioid user or per chronic opioid user. A higher per-capita supply of DCs and Medicare spending on CMT were inversely associated with younger, disabled Medicare beneficiaries obtaining an opioid prescription. However, neither measure was associated with opioid dosage among patients who obtained opioid prescriptions. Copyright © 2016. Published by Elsevier Inc.

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.

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.

tDCS Modulates Visual Gamma Oscillations and Basal Alpha Activity in Occipital Cortices: Evidence from MEG.

PubMed

Wilson, Tony W; McDermott, Timothy J; Mills, Mackenzie S; Coolidge, Nathan M; Heinrichs-Graham, Elizabeth

2018-05-01

Transcranial direct-current stimulation (tDCS) is now a widely used method for modulating the human brain, but the resulting physiological effects are not understood. Recent studies have combined magnetoencephalography (MEG) with simultaneous tDCS to evaluate online changes in occipital alpha and gamma oscillations, but no study to date has quantified the offline (i.e., after tDCS) alterations in these responses. Thirty-five healthy adults received active or sham anodal tDCS to the occipital cortices, and then completed a visual stimulation paradigm during MEG that is known to elicit robust gamma and alpha oscillations. The resulting MEG data were imaged and peak voxel time series were extracted to evaluate tDCS effects. We found that tDCS to the occipital increased the amplitude of local gamma oscillations, and basal alpha levels during the baseline. tDCS was also associated with network-level effects, including increased gamma oscillations in the prefrontal cortex, parietal, and other visual attention regions. Finally, although tDCS did not modulate peak gamma frequency, this variable was inversely correlated with gamma amplitude, which is consistent with a GABA-gamma link. In conclusion, tDCS alters gamma oscillations and basal alpha levels. The net offline effects on gamma activity are consistent with the view that anodal tDCS decreases local GABA.

Monitoring blood flow responses during topical ALA-PDT

PubMed Central

Becker, Theresa L.; Paquette, Anne D.; Keymel, Kenneth R.; Henderson, Barbara W.; Sunar, Ulas

2011-01-01

Photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) is currently used as a clinical treatment for nonmelanoma skin cancers. In order to optimize PDT treatment, vascular disruption early in treatment must be identified and prevented. We present blood flow responses to topical ALA-PDT in a preclinical model and basal cell carcinoma patients assessed by diffuse correlation spectroscopy (DCS). Our results show that ALA-PDT induced early blood flow changes and these changes were irradiance dependent. It is clear that there exists considerable variation in the blood flow responses in patients from lesion to lesion. Monitoring blood flow parameter may be useful for assessing ALA-PDT response and planning. PMID:21326642

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.

Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations and Resting-State Functional Connectivity of the Left Temporo-Parietal Junction in Patients With Schizophrenia

PubMed Central

Mondino, Marine; Jardri, Renaud; Suaud-Chagny, Marie-Françoise; Saoud, Mohamed; Poulet, Emmanuel; Brunelin, Jérôme

2016-01-01

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring. PMID:26303936

Is Transcranial Direct Current Stimulation an Effective Predictor for Invasive Occipital Nerve Stimulation Treatment Success in Fibromyalgia Patients?

PubMed

Plazier, Mark; Tchen, Stephanie; Ost, Jan; Joos, Kathleen; De Ridder, Dirk; Vanneste, Sven

2015-10-01

Fibromyalgia is a disorder distinguished by pervasive musculoskeletal pain that has pervasive effects on affected individuals magnifying the importance of finding a safe and viable treatment option. The goal of this study is to investigate if transcranial direct current stimulation (tDCS) treatment can predict the outcome of occipital nerve field stimulation (ONFS) via a subcutaneous electrode. Nine patients with fibromyalgia were selected fulfilling the American College of Rheumatology-90 criteria. The patients were implanted with a subcutaneous trial-lead in the C2 dermatome innervated by the occipital nerve. After the treatment phase of ONFS using a C2 implant, each patient participated in three sessions of tDCS. Stimulation outcomes for pain suppression were examined between the two methods to determine possible correlations. Positive correlation of stimulation effect was noted between the numeric rating scale changes for pain obtained by tDCS treatments and short-term measures of ONFS, but no correlation was noted between tDCS and long-term ONFS outcomes. A correlation also was noted between short-term ONS C2 implant pain suppression and long-term ONS C2 implant treatment success. This pilot study suggests that tDCS is a predictive measure for success of OFNS in short-term but cannot be used as a predictive measure for success of long-term OFNS. Our data confirm previous findings that ONFS via an implanted electrode can improve fibromyalgia pain in a placebo-controlled way and exert a long-term pain suppression effect for ONFS via an implanted electrode. © 2015 International Neuromodulation Society.

Transcranial Direct Current Stimulation Modulates Neuronal Activity and Learning in Pilot Training

PubMed Central

Choe, Jaehoon; Coffman, Brian A.; Bergstedt, Dylan T.; Ziegler, Matthias D.; Phillips, Matthew E.

2016-01-01

Skill acquisition requires distributed learning both within (online) and across (offline) days to consolidate experiences into newly learned abilities. In particular, piloting an aircraft requires skills developed from extensive training and practice. Here, we tested the hypothesis that transcranial direct current stimulation (tDCS) can modulate neuronal function to improve skill learning and performance during flight simulator training of aircraft landing procedures. Thirty-two right-handed participants consented to participate in four consecutive daily sessions of flight simulation training and received sham or anodal high-definition-tDCS to the right dorsolateral prefrontal cortex (DLPFC) or left motor cortex (M1) in a randomized, double-blind experiment. Continuous electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS) were collected during flight simulation, n-back working memory, and resting-state assessments. tDCS of the right DLPFC increased midline-frontal theta-band activity in flight and n-back working memory training, confirming tDCS-related modulation of brain processes involved in executive function. This modulation corresponded to a significantly different online and offline learning rates for working memory accuracy and decreased inter-subject behavioral variability in flight and n-back tasks in the DLPFC stimulation group. Additionally, tDCS of left M1 increased parietal alpha power during flight tasks and tDCS to the right DLPFC increased midline frontal theta-band power during n-back and flight tasks. These results demonstrate a modulation of group variance in skill acquisition through an increasing in learned skill consistency in cognitive and real-world tasks with tDCS. Further, tDCS performance improvements corresponded to changes in electrophysiological and blood-oxygenation activity of the DLPFC and motor cortices, providing a stronger link between modulated neuronal function and behavior. PMID:26903841

Intra-hippocampal D-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats.

PubMed

Portero-Tresserra, Marta; Martí-Nicolovius, Margarita; Tarrés-Gatius, Mireia; Candalija, Ana; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

2018-05-01

Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats. We investigated the effects of pre-training infusions of DCS (10 μg/hemisphere) in the ventral hippocampus on two hippocampal-dependent learning tasks, the social transmission of food preference (STFP), and the Morris water maze (MWM). The results revealed that infusions of DCS administered before the acquisition sessions rescued deficits in the STFP retention and MWM reversal learning in old rats. DCS also significantly increased the hippocampal levels of synaptophysin in old rats, which correlated with STFP and MWM performance in all tests. Moreover, although the levels of the GluN1 subunit correlated with the MWM acquisition and reversal, DCS did not enhance the expression of such synaptic protein. The present behavioral results support the role of DCS as a cognitive enhancer and suggest that enhancing the function of NMDARs and synaptic plasticity in the hippocampus may be related to improvement in social memory and spatial learning reversal in aged animals.

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

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.

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

Coxiella burnetii Induces Inflammatory Interferon-Like Signature in Plasmacytoid Dendritic Cells: A New Feature of Immune Response in Q Fever

PubMed Central

Ka, Mignane B.; Mezouar, Soraya; Ben Amara, Amira; Raoult, Didier; Ghigo, Eric; Olive, Daniel; Mege, Jean-Louis

2016-01-01

Plasmacytoid dendritic cells (pDCs) play a major role in antiviral immunity via the production of type I interferons (IFNs). There is some evidence that pDCs interact with bacteria but it is not yet clear whether they are protective or contribute to bacterial pathogenicity. We wished to investigate whether Coxiella burnetii, the agent of Q fever, interacts with pDCs. The stimulation of pDCs with C. burnetii increased the expression of activation and migratory markers (CD86 and CCR7) as determined by flow cytometry and modulated gene expression program as revealed by a microarray approach. Indeed, genes encoding for pro-inflammatory cytokines, chemokines, and type I INF were up-regulated. The up-regulation of type I IFN was correlated with an increase in IFN-α release by C. burnetii-stimulated pDCs. We also investigated pDCs in patients with Q fever endocarditis. Using flow cytometry and a specific gating strategy, we found that the number of circulating pDCs was significantly lower in patients with Q fever endocarditis as compared to healthy donors. In addition, the remaining circulating pDCs expressed activation and migratory markers. As a whole, our study identified non-previously reported activation of pDCs by C. burnetii and their modulation during Q fever. PMID:27446817

The temporary and accumulated effects of transcranial direct current stimulation for the treatment of advanced Parkinson’s disease monkeys

PubMed Central

Li, Hao; Lei, Xiaoguang; Yan, Ting; Li, Hongwei; Huang, Baihui; Li, Ling; Xu, Liqi; Liu, Li; Chen, Nanhui; Lü, Longbao; Ma, Yuanye; Xu, Lin; Li, Jiali; Wang, Zhengbo; Zhang, Baorong; Hu, Xintian

2015-01-01

Transcranial direct current stimulation (tDCS) is a useful noninvasive technique of cortical brain stimulation for the treatment of neurological disorders. Clinical research has demonstrated tDCS with anodal stimulation of primary motor cortex (M1) in Parkinson’s disease (PD) patients significantly improved their motor function. However, few studies have been focused on the optimization of parameters which contributed significantly to the treatment effects of tDCS and exploration of the underline neuronal mechanisms. Here, we used different stimulation parameters of anodal tDCS on M1 for the treatment of aged advanced PD monkeys induced with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) administration, and then analyzed the temporary and accumulated effects of tDCS treatment. The results indicated anodal tDCS on M1 very significantly improved motor ability temporarily; importantly, the treatment effects of anodal tDCS on M1 were quantitatively correlated to the accumulated stimulation instead of the stimuli intensity or duration respectively. In addition, c-fos staining showed tDCS treatment effects activated the neurons both in M1 and substantia nigra (SN). Therefore, we propose that long time and continue anodal tDCS on M1 is a better strategy to improve the motor symptoms of PD than individual manipulation of stimuli intensity or duration. PMID:26220760

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.

Simultaneous tDCS-fMRI Identifies Resting State Networks Correlated with Visual Search Enhancement.

PubMed

Callan, Daniel E; Falcone, Brian; Wada, Atsushi; Parasuraman, Raja

2016-01-01

This study uses simultaneous transcranial direct current stimulation (tDCS) and functional MRI (fMRI) to investigate tDCS modulation of resting state activity and connectivity that underlies enhancement in behavioral performance. The experiment consisted of three sessions within the fMRI scanner in which participants conducted a visual search task: Session 1: Pre-training (no performance feedback), Session 2: Training (performance feedback given), Session 3: Post-training (no performance feedback). Resting state activity was recorded during the last 5 min of each session. During the 2nd session one group of participants underwent 1 mA tDCS stimulation and another underwent sham stimulation over the right posterior parietal cortex. Resting state spontaneous activity, as measured by fractional amplitude of low frequency fluctuations (fALFF), for session 2 showed significant differences between the tDCS stim and sham groups in the precuneus. Resting state functional connectivity from the precuneus to the substantia nigra, a subcortical dopaminergic region, was found to correlate with future improvement in visual search task performance for the stim over the sham group during active stimulation in session 2. The after-effect of stimulation on resting state functional connectivity was measured following a post-training experimental session (session 3). The left cerebellum Lobule VIIa Crus I showed performance related enhancement in resting state functional connectivity for the tDCS stim over the sham group. The ability to determine the relationship that the relative strength of resting state functional connectivity for an individual undergoing tDCS has on future enhancement in behavioral performance has wide ranging implications for neuroergonomic as well as therapeutic, and rehabilitative applications.

Effects of Fronto-Temporal Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations and Resting-State Functional Connectivity of the Left Temporo-Parietal Junction in Patients With Schizophrenia.

PubMed

Mondino, Marine; Jardri, Renaud; Suaud-Chagny, Marie-Françoise; Saoud, Mohamed; Poulet, Emmanuel; Brunelin, Jérôme

2016-03-01

Auditory verbal hallucinations (AVH) in patients with schizophrenia are associated with abnormal hyperactivity in the left temporo-parietal junction (TPJ) and abnormal connectivity between frontal and temporal areas. Recent findings suggest that fronto-temporal transcranial Direct Current stimulation (tDCS) with the cathode placed over the left TPJ and the anode over the left prefrontal cortex can alleviate treatment-resistant AVH in patients with schizophrenia. However, brain correlates of the AVH reduction are unclear. Here, we investigated the effect of tDCS on the resting-state functional connectivity (rs-FC) of the left TPJ. Twenty-three patients with schizophrenia and treatment-resistant AVH were randomly allocated to receive 10 sessions of active (2 mA, 20 min) or sham tDCS (2 sessions/d for 5 d). We compared the rs-FC of the left TPJ between patients before and after they received active or sham tDCS. Relative to sham tDCS, active tDCS significantly reduced AVH as well as the negative symptoms. Active tDCS also reduced rs-FC of the left TPJ with the left anterior insula and the right inferior frontal gyrus and increased rs-FC of the left TPJ with the left angular gyrus, the left dorsolateral prefrontal cortex and the precuneus. The reduction of AVH severity was correlated with the reduction of the rs-FC between the left TPJ and the left anterior insula. These findings suggest that the reduction of AVH induced by tDCS is associated with a modulation of the rs-FC within an AVH-related brain network, including brain areas involved in inner speech production and monitoring. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Monitoring and assessment of tumor hemodynamics during pleural PDT

NASA Astrophysics Data System (ADS)

Ong, Yi Hong; Kim, Michele M.; Penjweini, Rozhin; Rodriguez, Carmen E.; Dimofte, Andrea; Finlay, Jarod C.; Busch, Theresa M.; Yodh, Arjun G.; Cengel, Keith A.; Singhal, Sunil; Zhu, Timothy C.

2017-02-01

Intrapleural photodynamic therapy (PDT) has been used in combination with lung sparing surgery to treat patients with malignant pleural mesothelioma. The light, photosensitizers and tissue oxygen are the three most important factors required by type II PDT to produce singlet oxygen, 1O2, which is the main photocytotoxic agent that damages the tumor vasculature and stimulates the body's anti-tumor immune response. Although light fluence rate and photosensitizer concentrations are routinely monitored during clinical PDT, there is so far a lack of a Food and Drug Administration (FDA)-approved non-invasive technique that can be employed clinically to monitor tissue oxygen in vivo. In this paper, we demonstrated that blood flow correlates well with tissue oxygen concentration during PDT and can be used in place of [3O2] to calculate reacted singlet oxygen concentration [1O2]rx using the macroscopic singlet oxygen model. Diffuse correlation spectroscopy (DCS) was used to monitor the change in tissue blood flow non-invasively during pleural PDT. A contact probe with three source and detectors separations, 0.4, 0.7 and 1.0-cm, was sutured to the pleural cavity wall of the patients after surgical resection of the pleural mesothelioma tumor to monitor the tissue blood flow during intraoperative PDT treatment. The changes of blood flow during PDT of 2 patients are found to be in good correlation with the treatment light fluence rate recorded by the isotropic detector placed adjacent to the DCS probe. [1O2]rx calculated based on light fluence, mean photosensitizer concentration, and relative blood flow was found to be 32% higher in patient #4 (0.50mM) than that for patient #3 (0.38mM).

Diffuse cerebral symptoms in convalescents from cerebral infarction and myocardial infarction.

PubMed

Leegaard, O F

1983-06-01

In order to evaluate occurrence and cause of a number of diffuse cerebral symptoms (DCS), such as impaired memory, inability to concentrate, emotional instability, irritability, etc., 44 survivors of cerebral infarction (CI) and 40 survivors of myocardial infarction (MI) were seen 6-26 months after onset for psychometric testing and an interview about DCS. Although surprisingly common in both groups, DCS were significantly more frequent in CI patients than in MI patients. 1/2 of the former and 1/3 of the latter complained of 5 or more symptoms. In contrast, a significant difference in test performance was demonstrated in only 1 of 4 tests. There was no significant correlation between the number of DCS and test performance. In both groups, DCS occurrence was independent of age, whereas in the MI group, but not in the CI group, test performance was inversely related to age. In the CI group, DCS occurrence was not significantly related to size or site of the infarction. The results indicate that an organic brain damage cannot be the sole cause of DCS, and it is suggested that some of the symptoms are manifestations of a stress response syndrome provoked by insufficient coping with the consequences of the disease.

Dive Risk Factors, Gas Bubble Formation, and Decompression Illness in Recreational SCUBA Diving: Analysis of DAN Europe DSL Data Base.

PubMed

Cialoni, Danilo; Pieri, Massimo; Balestra, Costantino; Marroni, Alessandro

2017-01-01

Introduction: The popularity of SCUBA diving is steadily increasing together with the number of dives and correlated diseases per year. The rules that govern correct decompression procedures are considered well known even if the majority of Decompression Sickness (DCS) cases are considered unexpected confirming a bias in the "mathematical ability" to predict DCS by the current algorithms. Furthermore, little is still known about diving risk factors and any individual predisposition to DCS. This study provides an in-depth epidemiological analysis of the diving community, to include additional risk factors correlated with the development of circulating bubbles and DCS. Materials and Methods: An originally developed database (DAN DB) including specific questionnaires for data collection allowed the statistical analysis of 39,099 electronically recorded open circuit dives made by 2,629 European divers (2,189 males 83.3%, 440 females 16.7%) over 5 years. The same dive parameters and risk factors were investigated also in 970 out of the 39,099 collected dives investigated for bubble formation, by 1-min precordial Doppler, and in 320 sea-level dives followed by DCS symptoms. Results: Mean depth and GF high of all the recorded dives were 27.1 m, and 0.66, respectively; the average ascent speed was lower than the currently recommended "safe" one (9-10 m/min). We found statistically significant relationships between higher bubble grades and BMI, fat mass, age, and diving exposure. Regarding incidence of DCS, we identified additional non-bubble related risk factors, which appear significantly related to a higher DCS incidence, namely: gender, strong current, heavy exercise, and workload during diving. We found that the majority of the recorded DCS cases were not predicted by the adopted decompression algorithm and would have therefore been defined as "undeserved." Conclusion: The DAN DB analysis shows that most dives were made in a "safe zone," even if data show an evident "gray area" in the "mathematical" ability to predict DCS by the current algorithms. Some other risk factors seem to influence the possibility to develop DCS, irrespective of their effect on bubble formation, thus suggesting the existence of some factors influencing or enhancing the effects of bubbles.

Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions.

PubMed

Ammann, Claudia; Lindquist, Martin A; Celnik, Pablo A

It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. 2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability. Copyright © 2017 Elsevier Inc. All rights reserved.

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 transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production.

PubMed

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

2011-12-01

Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A-tDCS by employing the semantic interference (SI-)Effect - a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language-related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro-rehabilitation of frontal language functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-01-01

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

MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells

PubMed Central

Botta, C; Cucè, M; Pitari, M R; Caracciolo, D; Gullà, A; Morelli, E; Riillo, C; Biamonte, L; Gallo Cantafio, M E; Prabhala, R; Mignogna, C; Di Vito, A; Altomare, E; Amodio, N; Di Martino, M T; Correale, P; Rossi, M; Giordano, A; Munshi, N C; Tagliaferri, P; Tassone, P

2018-01-01

Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced expression of miR-29b counteracted pro-inflammatory pathways, including signal transducer and activator of transcription 3 and nuclear factor-κB, and cytokine/chemokine signaling networks, which correlated with patients’ adverse prognosis and development of bone disease. Moreover, miR-29b downregulated interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a Th17 inflammatory response. All together, these effects translated into strong anti-proliferative activity and reduction of genomic instability of MM cells. Our study demonstrates that MM reprograms the DCs functional phenotype by downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM cell growth and survival. These results underscore miR-29b as an innovative and attractive candidate for miRNA-based immune therapy of MM. PMID:29158557

Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.

PubMed

Posch, Wilfried; Steger, Marion; Knackmuss, Ulla; Blatzer, Michael; Baldauf, Hanna-Mari; Doppler, Wolfgang; White, Tommy E; Hörtnagl, Paul; Diaz-Griffero, Felipe; Lass-Flörl, Cornelia; Hackl, Hubert; Moris, Arnaud; Keppler, Oliver T; Wilflingseder, Doris

2015-06-01

DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.

Effects of Anodal High-Definition Transcranial Direct Current Stimulation on Bilateral Sensorimotor Cortex Activation During Sequential Finger Movements: An fNIRS Study.

PubMed

Muthalib, Makii; Besson, Pierre; Rothwell, John; Ward, Tomas; Perrey, Stephane

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive electrical brain stimulation technique that can modulate cortical neuronal excitability and activity. This study utilized functional near infrared spectroscopy (fNIRS) neuroimaging to determine the effects of anodal high-definition (HD)-tDCS on bilateral sensorimotor cortex (SMC) activation. Before (Pre), during (Online), and after (Offline) anodal HD-tDCS (2 mA, 20 min) targeting the left SMC, eight healthy subjects performed a simple finger sequence (SFS) task with their right or left hand in an alternating blocked design (30-s rest and 30-s SFS task, repeated five times). In order to determine the level of bilateral SMC activation during the SFS task, an Oxymon MkIII fNIRS system was used to measure from the left and right SMC, changes in oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin concentration values. The fNIRS data suggests a finding that compared to the Pre condition both the "Online" and "Offline" anodal HD-tDCS conditions induced a significant reduction in bilateral SMC activation (i.e., smaller decrease in HHb) for a similar motor output (i.e., SFS tap rate). These findings could be related to anodal HD-tDCS inducing a greater efficiency of neuronal transmission in the bilateral SMC to perform the same SFS task.

Transforming growth factor-β1 deteriorates microrheological characteristics and motility of mature dendritic cells in concentration-dependent fashion.

PubMed

Zheng, Qinni; Long, Jinhua; Jia, Binbin; Xu, Xiaoli; Zhang, Chunlin; Li, Long; Wen, Zongyao; Jin, Feng; Yao, Weijuan; Zeng, Zhu

2014-01-01

Dendritic cells (DCs) are potent and specialized antigen-presenting cells that play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Tumor cells can escape from immune attack by secreting suppressive cytokines which solely or cooperatively impair the immune function and microrheological properties of DCs. However, the underlying mechanisms are not fully defined. Transforming growth factor-β1 (TGF-β1) has been identified as a major cytokine in the tumor microenvironment. To determine the effects of TGF-β1 on mature DCs (mDCs) from microrheological viewpoint, cells were treated with different concentrations of TGF-β1. The results showed that the impaired microrheological parameters, including osmotic fragility, electrophoretic mobility, deformability, membrane fluidity, F-actin organization and so on, as well as motilities of mDCs relied heavily on TGF-β1 concentration. Moreover, these changes were correlated with the expression levels of fascin1, cofilin1, phosphorylated cofilin1 and profilin, this could be one of the crucial aspects of immune escape mechanisms of tumors, hinting that the signal pathway of TGF-β1 should be blocked in appropriate way before performing DCs-based immunotherapy against cancer. It is clinically important to understand the biological behavior of DCs and immune escape mechanism of tumor as well as how to improve efficiency of the anti-tumor therapy based on DCs.

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

Prefrontal cortex stimulation does not affect emotional bias, but may slow emotion identification.

PubMed

Nord, Camilla L; Forster, Sophie; Halahakoon, D Chamith; Penton-Voak, Ian S; Munafò, Marcus R; Roiser, Jonathan P

2017-05-01

Transcranial direct current stimulation (tDCS) has recently garnered attention as a putative depression treatment. However, the cognitive mechanisms by which it exerts an antidepressant effect are unclear: tDCS may directly alter 'hot' emotional processing biases, or alleviate depression through changes in 'cold' (non-emotional) cognitive function. Here, 75 healthy participants performed a facial emotion identification task during 20 minutes of anodal or sham tDCS over the left dorsolateral prefrontal cortex (DLPFC) in a double-blind, within-subject crossover design. A subset of 31 participants additionally completed a task measuring attentional distraction during stimulation. Compared to sham stimulation, anodal tDCS of the left DLPFC resulted in an increase in response latency across all emotional conditions. Bayesian analysis showed definitively that tDCS exerted no emotion-dependent effect on behaviour. Thus, we demonstrate that anodal tDCS produces a general, rather than an emotion-specific, effect. We also report a preliminary finding in the subset of participants who completed the distractibility task: increased distractibility during active stimulation correlated significantly with the degree to which tDCS slowed emotion identification. Our results provide insight into the possible mechanisms by which DLPFC tDCS may treat symptoms of depression, suggesting that it may not alter emotional biases, but instead may affect 'cold' cognitive processes. © The Author (2017). Published by Oxford University Press.

Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies

PubMed Central

Lindner, Claus; Johansson, Johannes; Weigel, Udo M.; Halperin, Irene; Hanzu, Felicia A.; Durduran, Turgut

2016-01-01

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs′) at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25–44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening. PMID:26815533

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

PubMed

Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

2017-02-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy

PubMed Central

Mucsi, Ashley D.; Meng, Junchen; Yan, Jiacong; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D.; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W.

2017-01-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell–DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1–dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin–cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1–dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell–mediated DC suppression in a contact-dependent manner. PMID:28082358

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

PubMed

Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Zimmer, Claus; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

2015-07-01

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

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.

Adenoviral-transduced dendritic cells are susceptible to suppression by T regulatory cells and promote interleukin 17 production.

PubMed

Wang, Adele Y; Crome, Sarah Q; Jenkins, Kristina M; Medin, Jeffrey A; Bramson, Jonathan L; Levings, Megan K

2011-03-01

Dendritic cell (DC) vaccines offer a robust platform for the development of cancer vaccines, but their effectiveness is thought to be limited by T regulatory cells (Tregs). Recombinant adenoviruses (RAdV) have been used successfully to engineer tumor antigen expression in DCs, but the impact of virus transduction on susceptibility to suppression by Tregs is unknown. We investigated the functional consequences of exposure to adenovirus on interactions between human monocyte-derived DCs and Tregs. Since the development of Tregs is linked to that of pro-inflammatory Th17 cells, the role of Th17 cells and IL-17-producing Tregs in the context of DC-based immunotherapies was also investigated. We found that Tregs potently suppressed the co-stimulatory capacity of RAdV-transduced DCs, regardless of whether the DCs were maturated by inflammatory cytokines or by exposure to Th1 or Th17 cells. Furthermore, exposure of Tregs to RAdV-exposed DCs increased IL-17 production and suppressive capacity, and correlated with enhanced secretion of IL-1β and IL-6 by DCs. The findings that DCs exposed to RAdV are suppressed by Tregs, promote Treg plasticity, and enhance Treg suppression indicates that strategies to limit Tregs will be required to enhance the efficacy of such DC-based immunotherapies.

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.

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.

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

PubMed

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

2018-07-01

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

The ''self-stirred'' genome: Bulk and surface dynamics of the chromatin globule

NASA Astrophysics Data System (ADS)

Zidovska, Alexandra

Chromatin structure and dynamics control all aspects of DNA biology yet are poorly understood. In interphase, time between two cell divisions, chromatin fills the cell nucleus in its minimally condensed polymeric state. Chromatin serves as substrate to a number of biological processes, e.g. gene expression and DNA replication, which require it to become locally restructured. These are energy-consuming processes giving rise to non-equilibrium dynamics. Chromatin dynamics has been traditionally studied by imaging of fluorescently labeled nuclear proteins and single DNA-sites, thus focusing only on a small number of tracer particles. Recently, we developed an approach, displacement correlation spectroscopy (DCS) based on time-resolved image correlation analysis, to map chromatin dynamics simultaneously across the whole nucleus in cultured human cells. DCS revealed that chromatin movement was coherent across large regions (4-5 μm) for several seconds. Regions of coherent motion extended beyond the boundaries of single-chromosome territories, suggesting elastic coupling of motion over length scales much larger than those of genes. These large-scale, coupled motions were ATP-dependent and unidirectional for several seconds. Following these observations, we developed a hydrodynamic theory of active chromatin dynamics, using the two-fluid model and describing the content of cell nucleus as a chromatin solution, which is subject to both passive thermal fluctuations and active (ATP-consuming) scalar and vector events. In this work we continue in our efforts to elucidate the mechanism and function of the chromatin dynamics in interphase. We investigate the chromatin interactions with the nuclear envelope and compare the surface dynamics of the chromatin globule with its bulk dynamics.

Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

PubMed

Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

2016-06-01

No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

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

PubMed

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

2017-07-15

Transcranial Direct Current Stimulation (tDCS) of the prefrontal cortex (PFC) can be used for probing functional brain connectivity and meets general interest as novel therapeutic intervention in psychiatric and neurological disorders. Along with a more extensive use, it is important to understand the interplay between neural systems and stimulation protocols requiring basic methodological work. Here, we examined the test-retest (TRT) characteristics of tDCS-induced modulations in resting-state functional-connectivity MRI (RS fcMRI). Twenty healthy subjects received 20minutes of either active or sham tDCS of the dorsolateral PFC (2mA, anode over F3 and cathode over F4, international 10-20 system), preceded and ensued by a RS fcMRI (10minutes each). All subject underwent three tDCS sessions with one-week intervals in between. Effects of tDCS on RS fcMRI were determined at an individual as well as at a group level using both ROI-based and independent-component analyses (ICA). To evaluate the TRT reliability of individual active-tDCS and sham effects on RS fcMRI, voxel-wise intra-class correlation coefficients (ICC) of post-tDCS maps between testing sessions were calculated. For both approaches, results revealed low reliability of RS fcMRI after active tDCS (ICC (2,1) = -0.09 - 0.16). Reliability of RS fcMRI (baselines only) was low to moderate for ROI-derived (ICC (2,1) = 0.13 - 0.50) and low for ICA-derived connectivity (ICC (2,1) = 0.19 - 0.34). Thus, for ROI-based analyses, the distribution of voxel-wise ICC was shifted to lower TRT reliability after active, but not after sham tDCS, for which the distribution was similar to baseline. The intra-individual variation observed here resembles variability of tDCS effects in motor regions and may be one reason why in this study robust tDCS effects at a group level were missing. The data can be used for appropriately designing large scale studies investigating methodological issues such as sources of variability and localisation of tDCS effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship of Exercise, Age, and Gender on Decompression Sickness and Venous Gas Emboli During 2-Hour Oxygen Prebreathe Prior to Hypobaric Exposure

NASA Technical Reports Server (NTRS)

Conkin, J.; Gernhardt, M. L.; Foster, P. P.; Pilmanis, A. A.; Butler, B. D.; Beltran, E.; Fife, C. E.; Vann, R. D.; Gerth, W. A.; Loftin, K. C.;

Individual differences in learning correlate with modulation of brain activity induced by transcranial direct current stimulation

PubMed Central

Falcone, Brian; Wada, Atsushi; Parasuraman, Raja

2018-01-01

Transcranial direct current stimulation (tDCS) has been shown to enhance cognitive performance on a variety of tasks. It is hypothesized that tDCS enhances performance by affecting task related cortical excitability changes in networks underlying or connected to the site of stimulation facilitating long term potentiation. However, many recent studies have called into question the reliability and efficacy of tDCS to induce modulatory changes in brain activity. In this study, our goal is to investigate the individual differences in tDCS induced modulatory effects on brain activity related to the degree of enhancement in performance, providing insight into this lack of reliability. In accomplishing this goal, we used functional magnetic resonance imaging (fMRI) concurrently with tDCS stimulation (1 mA, 30 minutes duration) using a visual search task simulating real world conditions. The experiment consisted of three fMRI sessions: pre-training (no performance feedback), training (performance feedback which included response accuracy and target location and either real tDCS or sham stimulation given), and post-training (no performance feedback). The right posterior parietal cortex was selected as the site of anodal tDCS based on its known role in visual search and spatial attention processing. Our results identified a region in the right precentral gyrus, known to be involved with visual spatial attention and orienting, that showed tDCS induced task related changes in cortical excitability that were associated with individual differences in improved performance. This same region showed greater activity during the training session for target feedback of incorrect (target-error feedback) over correct trials for the tDCS stim over sham group indicating greater attention to target features during training feedback when trials were incorrect. These results give important insight into the nature of neural excitability induced by tDCS as it relates to variability in individual differences in improved performance shedding some light the apparent lack of reliability found in tDCS research. PMID:29782510

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

The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity.

PubMed

Amadi, Ugwechi; Allman, Claire; Johansen-Berg, Heidi; Stagg, Charlotte J

2015-01-01

The relative timing of plasticity-induction protocols is known to be crucial. For example, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability and typically enhances plasticity, can impair performance if it is applied before a motor learning task. Such timing-dependent effects have been ascribed to homeostatic plasticity, but the specific synaptic site of this interaction remains unknown. We wished to investigate the synaptic substrate, and in particular the role of inhibitory signaling, underpinning the behavioral effects of anodal tDCS in homeostatic interactions between anodal tDCS and motor learning. We used transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibitory signaling following tDCS and motor learning. Each subject participated in four experimental sessions and data were analyzed using repeated measures ANOVAs and post-hoc t-tests as appropriate. As predicted, we found that anodal tDCS prior to the motor task decreased learning rates. This worsening of learning after tDCS was accompanied by a correlated increase in GABAA activity, as measured by TMS-assessed short interval intra-cortical inhibition (SICI). This provides the first direct demonstration in humans that inhibitory synapses are the likely site for the interaction between anodal tDCS and motor learning, and further, that homeostatic plasticity at GABAA synapses has behavioral relevance in humans. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation

NASA Astrophysics Data System (ADS)

Granelli-Piperno, Angela; Golebiowska, Angelika; Trumpfheller, Christine; Siegal, Frederick P.; Steinman, Ralph M.

2004-05-01

Dendritic cells (DCs) undergo maturation during virus infection and thereby become potent stimulators of cell-mediated immunity. HIV-1 replicates in immature DCs, but we now find that infection is not accompanied by many components of maturation in either infected cells or uninfected bystanders. The infected cultures do not develop potent stimulating activity for the mixed leukocyte reaction (MLR), and the DCs producing HIV-1 gag p24 do not express CD83 and DC-lysosome-associated membrane protein maturation markers. If different maturation stimuli are applied to DCs infected with HIV-1, the infected cells selectively fail to mature. When DCs from HIV-1-infected patients are infected and cultured with autologous T cells, IL-10 was produced in 6 of 10 patients. These DC-T cell cocultures could suppress another immune response, the MLR. The regulation was partially IL-10-dependent and correlated in extent with the level of IL-10 produced. Suppressor cells only developed from infected patients, rather than healthy controls, and the DCs had to be exposed to live virus rather than HIV-1 gag peptides or protein. These results indicate that HIV-1-infected DCs have two previously unrecognized means to evade immune responses: maturation can be blocked reducing the efficacy of antigen presentation from infected cells, and T cell-dependent suppression can be induced.

Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation.

PubMed

Jamil, Asif; Batsikadze, Giorgi; Kuo, Hsiao-I; Labruna, Ludovica; Hasan, Alkomiet; Paulus, Walter; Nitsche, Michael A

2017-02-15

Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings. However, the need for longer-lasting effects, combined with marked inter-individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects. We systematically investigated the full DC intensity range (0.5-2.0 mA) for both anodal and cathodal tDCS in a sham-controlled repeated measures design, monitoring changes in motor-cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation. For both tDCS polarities, the excitability after-effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor-cortical excitability. Further, while intra-individual responses showed good reliability, inter-individual sensitivity to TMS accounted for a modest percentage of the variance in the early after-effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations. Contemporary non-invasive neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), have shown promising potential in both restituting impairments in cortical physiology in clinical settings, as well as modulating cognitive abilities in the healthy population. However, neuroplastic after-effects of tDCS are highly dependent on stimulation parameters, relatively short lasting, and not expectedly uniform between individuals. The present study systematically investigates the full range of current intensity between 0.5 and 2.0 mA on left primary motor cortex (M1) plasticity, as well as the impact of individual-level covariates on explaining inter-individual variability. Thirty-eight healthy subjects were divided into groups of anodal and cathodal tDCS. Five DC intensities (sham, 0.5, 1.0, 1.5 and 2.0 mA) were investigated in separate sessions. Using transcranial magnetic stimulation (TMS), 25 motor-evoked potentials (MEPs) were recorded before, and 10 time points up to 2 h following 15 min of tDCS. Repeated-measures ANOVAs indicated a main effect of intensity for both anodal and cathodal tDCS. With anodal tDCS, all active intensities resulted in equivalent facilitatory effects relative to sham while for cathodal tDCS, only 1.0 mA resulted in sustained excitability diminution. An additional experiment conducted to assess intra-individual variability revealed generally good reliability of 1.0 mA anodal tDCS (ICC(2,1) = 0.74 over the first 30 min). A post hoc analysis to discern sources of inter-individual variability confirmed a previous finding in which individual TMS SI 1mV (stimulus intensity for 1 mV MEP amplitude) sensitivity correlated negatively with 1.0 mA anodal tDCS effects on excitability. Our study thus provides further insights on the extent of non-linear intensity-dependent neuroplastic after-effects of anodal and cathodal tDCS. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Adaptive threshold hunting for the effects of transcranial direct current stimulation on primary motor cortex inhibition.

PubMed

Mooney, Ronan A; Cirillo, John; Byblow, Winston D

2018-06-01

Primary motor cortex excitability can be modulated by anodal and cathodal transcranial direct current stimulation (tDCS). These neuromodulatory effects may, in part, be dependent on modulation within gamma-aminobutyric acid (GABA)-mediated inhibitory networks. GABAergic function can be quantified non-invasively using adaptive threshold hunting paired-pulse transcranial magnetic stimulation (TMS). The previous studies have used TMS with posterior-anterior (PA) induced current to assess tDCS effects on inhibition. However, TMS with anterior-posterior (AP) induced current in the brain provides a more robust measure of GABA-mediated inhibition. The aim of the present study was to assess the modulation of corticomotor excitability and inhibition after anodal and cathodal tDCS using TMS with PA- and AP-induced current. In 16 young adults (26 ± 1 years), we investigated the response to anodal, cathodal, and sham tDCS in a repeated-measures double-blinded crossover design. Adaptive threshold hunting paired-pulse TMS with PA- and AP-induced current was used to examine separate interneuronal populations within M1 and their influence on corticomotor excitability and short- and long-interval inhibition (SICI and LICI) for up to 60 min after tDCS. Unexpectedly, cathodal tDCS increased corticomotor excitability assessed with AP (P = 0.047) but not PA stimulation (P = 0.74). SICI AP was reduced after anodal tDCS compared with sham (P = 0.040). Pearson's correlations indicated that SICI AP and LICI AP modulation was associated with corticomotor excitability after anodal (P = 0.027) and cathodal tDCS (P = 0.042). The after-effects of tDCS on corticomotor excitability may depend on the direction of the TMS-induced current used to make assessments, and on modulation within GABA-mediated inhibitory circuits.

Effects of transcranial direct current stimulation of the motor cortex on prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study.

PubMed

Muthalib, Makii; Kan, Benjamin; Nosaka, Kazunori; Perrey, Stephane

2013-01-01

This study investigated whether manipulation of motor cortex excitability by transcranial direct current stimulation (tDCS) modulates neuromuscular fatigue and functional near-infrared spectroscopy (fNIRS)-derived prefrontal cortex (PFC) activation. Fifteen healthy men (27.7 ± 8.4 years) underwent anodal (2 mA, 10 min) and sham (2 mA, first 30 s only) tDCS delivered to the scalp over the right motor cortex. Subjects initially performed a baseline sustained submaximal (30 % maximal voluntary isometric contraction, MVC) isometric contraction task (SSIT) of the left elbow flexors until task failure, which was followed 50 min later by either an anodal or sham treatment condition, then a subsequent posttreatment SSIT. Endurance time (ET), torque integral (TI), and fNIRS-derived contralateral PFC oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentration changes were determined at task failure. Results indicated that during the baseline and posttreatment SSIT, there were no significant differences in TI and ET, and increases in fNIRS-derived PFC activation at task failure were observed similarly regardless of the tDCS conditions. This suggests that the PFC neuronal activation to maintain muscle force production was not modulated by anodal tDCS.

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production.

PubMed

Wang, Yang; McGivern, David R; Cheng, Liang; Li, Guangming; Lemon, Stanley M; Niu, Junqi; Su, Lishan; Reszka-Blanco, Natalia J

2015-01-01

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production

PubMed Central

Wang, Yang; McGivern, David R; Cheng, Liang; Li, Guangming; Lemon, Stanley M; Niu, Junqi; Su, Lishan; Reszka-Blanco, Natalia J

2015-01-01

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production. PMID:26274905

Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

NASA Astrophysics Data System (ADS)

Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

2009-06-01

Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

Spontaneous eyelid closures link vigilance fluctuation with fMRI dynamic connectivity states

PubMed Central

Wang, Chenhao; Ong, Ju Lynn; Patanaik, Amiya; Chee, Michael W. L.

2016-01-01

Fluctuations in resting-state functional connectivity occur but their behavioral significance remains unclear, largely because correlating behavioral state with dynamic functional connectivity states (DCS) engages probes that disrupt the very behavioral state we seek to observe. Observing spontaneous eyelid closures following sleep deprivation permits nonintrusive arousal monitoring. During periods of low arousal dominated by eyelid closures, sliding-window correlation analysis uncovered a DCS associated with reduced within-network functional connectivity of default mode and dorsal/ventral attention networks, as well as reduced anticorrelation between these networks. Conversely, during periods when participants’ eyelids were wide open, a second DCS was associated with less decoupling between the visual network and higher-order cognitive networks that included dorsal/ventral attention and default mode networks. In subcortical structures, eyelid closures were associated with increased connectivity between the striatum and thalamus with the ventral attention network, and greater anticorrelation with the dorsal attention network. When applied to task-based fMRI data, these two DCS predicted interindividual differences in frequency of behavioral lapsing and intraindividual temporal fluctuations in response speed. These findings with participants who underwent a night of total sleep deprivation were replicated in an independent dataset involving partially sleep-deprived participants. Fluctuations in functional connectivity thus appear to be clearly associated with changes in arousal. PMID:27512040

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

PubMed

Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

2016-02-05

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

PubMed Central

Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

2016-01-01

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

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.

Involvement of suppressors of cytokine signaling in toll-like receptor-mediated block of dendritic cell differentiation.

PubMed

Bartz, Holger; Avalos, Nicole M; Baetz, Andrea; Heeg, Klaus; Dalpke, Alexander H

2006-12-15

Dendritic cells (DCs) are important sentinels within innate immunity, monitoring the presence of infectious microorganisms. They operate in 2 different maturation stages, with transition from immature to mature DCs being induced by activation of toll-like receptors (TLRs). However, TLRs are also expressed on precursor cells of DCs. Here we analyzed the effects of TLR stimulation during the process of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-mediated in vitro generation of immature DCs from precursor cells. We show that TLR triggering deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+ DCs. Similar results were obtained when differentiation of murine myeloid DCs from bone marrow cells was analyzed. The inhibitory effects were independent of soluble factors. TLR stimulation in DC precursor cells induced proteins of the suppressor of cytokine signaling family (SOCS), which correlated with loss of sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the inhibitory effects on DC generation observed for TLR stimulation. The results indicate that TLR stimulation during the period of DC generation interferes with and deviates DC differentiation and that these effects are mediated particularly by SOCS-1.

Lactobacillus paracasei CNCM I-4034 and its culture supernatant modulate Salmonella-induced inflammation in a novel transwell co-culture of human intestinal-like dendritic and Caco-2 cells.

PubMed

Bermudez-Brito, Miriam; Muñoz-Quezada, Sergio; Gómez-Llorente, Carolina; Matencio, Esther; Romero, Fernando; Gil, Angel

2015-04-01

The action of probiotics has been studied in vitro in cells isolated from both mice and humans, particularly enterocytes (IECs), dendritic cells (DCs) and co-cultures of peripheral DCs and IECs. Peripheral DCs and murine DCs differ from human gut DCs, and to date there are no data on the action of any probiotic on co-cultured human IECs and human intestinal DCs. To address this issue, a novel transwell model was used. Human IECs (Caco-2 cells) grown in the upper chamber of transwell filters were co-cultured with intestinal-like human DCs grown in the basolateral compartment of the transwells. The system was apically exposed for 4 h to live probiotic L. paracasei CNCM I-4034 obtained from the faeces of breastfed infants or to its cell-free culture supernatant (CFS) and challenged with Salmonella typhi. The secretion of pro- and anti-inflammatory cytokines in the basolateral compartment was determined by immunoassay, and the DC expression pattern of 20 TLR signaling pathway genes was analysed by PCR array. The presence of the live probiotic alone significantly increased IL-1β, IL-6, IL-8, TGF-β2, RANTES and IP-10 levels and decreased IL-12p40, IL-10, TGF- β1 and MIP-1α levels. This release was correlated with a significant increase in the expression of almost all TLR signaling genes. By contrast, incubation of the co-culture with CFS increased IL-1β, IL-6, TGF-β2 and IP-10 production only when Salmonella was present. This induction was correlated with an overall decrease in the expression of all TLR genes except TLR9, which was strongly up-regulated. The data presented here clearly indicate that L. paracasei CNCM I-4034 significantly increases the release of pro-inflammatory cytokines, enhances TLR signaling pathway activation and stimulates rather than suppresses the innate immune system. Furthermore, our findings provide evidence that the effects of probiotics in the presence of IECs and DCs differ from the effects of probiotics on cultures of each cell type alone, as reported by us earlier. Thus, co-culture systems such as the one described here are needed to characterise the effects of probiotics in vitro, highlighting the potential utility of such co-cultures as a model system.

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

Shang, Yu; Yu, Guoqiang, E-mail: guoqiang.yu@uky.edu

Conventional semi-infinite analytical solutions of correlation diffusion equation may lead to errors when calculating blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements in tissues with irregular geometries. Very recently, we created an algorithm integrating a Nth-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in homogenous tissues with arbitrary geometries for extraction of BFI (i.e., αD{sub B}). The purpose of this study is to extend the capability of the Nth-order linear algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries. The previous linear algorithm was modified to extract BFIs in different typesmore » of tissues simultaneously through utilizing DCS data at multiple source-detector separations. We compared the proposed linear algorithm with the semi-infinite homogenous solution in a computer model of adult head with heterogeneous tissue layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of the linear algorithm for extracting relative changes of cerebral blood flow (rCBF) in deep brain, we assigned ten levels of αD{sub B} in the brain layer with a step decrement of 10% while maintaining αD{sub B} values constant in other layers. Simulation results demonstrate the accuracy (errors < 3%) of high-order (N ≥ 5) linear algorithm in extracting BFIs in different tissue layers and rCBF in deep brain. By contrast, the semi-infinite homogenous solution resulted in substantial errors in rCBF (34.5% ≤ errors ≤ 60.2%) and BFIs in different layers. The Nth-order linear model simplifies data analysis, thus allowing for online data processing and displaying. Future study will test this linear algorithm in heterogeneous tissues with different levels of blood flow variations and noises.« less

Simultaneous quantitation of two direct acting hepatitis C antivirals (sofosbuvir and daclatasvir) by an HPLC-UV method designated for their pharmacokinetic study in rabbits.

PubMed

Atia, Noha N; El-Shaboury, Salwa R; El-Gizawy, Samia M; Abo-Zeid, Mohammad Nabil

2018-05-22

Sofosbuvir (SOF) and daclatasvir (DCS) are novel, recently developed direct acting antiviral agents characterized by potent anti-hepatitis C virus action. A fast and efficient HPLC-UV method was developed, validated and applied for simultaneous determination of SOF and DCS in pharmaceutical formulations and biological fluids based on coupling liquid-liquid extraction with ultrasound and dual wavelength detection at λ max ; 260 and 313 nm for SOF and DCS, respectively. This approach provided simple, sensitive, specific and cost-effective determination of the SOF-DCS mixture with good recoveries of the analytes from plasma. Analytes were separated within 7 min on C 18 analytical column with acetonitrile-10 mM acetate buffer of pH 5.0 at a flow rate of 1.0 mL min -1 . The linear ranges were 1-20 μg mL -1 for SOF and 0.6-6 μg mL -1 for DCS with correlation coefficients ≥0.9995. The detection limits in spiked rabbit plasma were 0.20 and 0.19 μg mL -1 for SOF and DCS, respectively. The method was validated according to ICH and US-FDA guidelines. Finally, the method was successfully applied for simultaneous pharmacokinetic studies of SOF and DCS in rabbits using rofecoxib as internal standard. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficient HPTLC-dual wavelength spectrodensitometric method for simultaneous determination of sofosbuvir and daclatasvir: Biological and pharmaceutical analysis.

PubMed

Abo-Zeid, Mohammad Nabil; El-Gizawy, Samia M; Atia, Noha N; El-Shaboury, Salwa R

2018-05-01

Sofosbuvir (SOF) and daclatasvir (DCS) are newly discovered anti-hepatitis C drugs that have direct antiviral activity. A novel and simple high-performance thin-layer chromatography (HPTLC) method was designed for simultaneous determination of SOF and DCS in miscellaneous matrices. The method adopts coupling HPTLC with dual wavelength spectrodensitometry. Consequently, this enabled sensitive, specific and cost-effective determination of the SOF-DCS mixture. The developed HPTLC procedure is based on a simple liquid-liquid extraction, enrichment of the analytes and subsequent chromatographic separation with UV detection. Separations were performed on HPTLC silica gel 60 F 254 aluminum plates with a mobile phase consisting of ethyl acetate-isopropanol (85:15, v/v). Dual wavelength scanning was carried out in the absorbance mode at 265 and 311 nm for SOF and DCS, respectively. The linear ranges were 40-640 and 20-320 ng band -1 for SOF and DCS, respectively with correlation coefficients of ≥0.9997. The detection limits were 11.3 and 6.5 ng band -1 for SOF and DCS, respectively indicating high sensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in human plasma with good percentage recovery (94.1-103.5%). Validation parameters were assessed according to ICH guidelines and US-FDA guidelines. Furthermore, the application was extended to analysis of SOF and DCS in their pharmaceutical formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

Modulating behavioral inhibition by tDCS combined with cognitive training.

PubMed

Ditye, Thomas; Jacobson, Liron; Walsh, Vincent; Lavidor, Michal

2012-06-01

Cognitive training is an effective tool to improve a variety of cognitive functions, and a small number of studies have now shown that brain stimulation accompanying these training protocols can enhance their effects. In the domain of behavioral inhibition, little is known about how training can affect this skill. As for transcranial direct current stimulation (tDCS), it was previously found that stimulation over the right inferior frontal gyrus (rIFG) facilitates behavioral inhibition performance and modulates its electrophysiological correlates. This study aimed to investigate this behavioral facilitation in the context of a learning paradigm by giving tDCS over rIFG repetitively over four consecutive days of training on a behavioral inhibition task (stop signal task (SST)). Twenty-two participants took part; ten participants were assigned to receive anodal tDCS (1.5 mA, 15 min), 12 were assigned to receive training but not active stimulation. There was a significant effect of training on learning and performance in the SST, and the integration of the training and rIFG-tDCS produced a more linear learning slope. Better performance was also found in the active stimulation group. Our findings show that tDCS-combined cognitive training is an effective tool for improving the ability to inhibit responses. The current study could constitute a step toward the use of tDCS and cognitive training as a therapeutic tool for cognitive control impairments in conditions such as attention-deficit hyperactivity disorder (ADHD) or schizophrenia.

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

PubMed

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

2017-01-01

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

Propolis modulates miRNAs involved in TLR-4 pathway, NF-κB activation, cytokine production and in the bactericidal activity of human dendritic cells.

PubMed

Conti, Bruno J; Santiago, Karina B; Cardoso, Eliza O; Freire, Paula P; Carvalho, Robson F; Golim, Marjorie A; Sforcin, José M

2016-12-01

Dendritic cells (DCs) are antigen-presenting cells, essential for recognition and presentation of pathogens to T cells. Propolis, a resinous material produced by bees from various plants, exhibits numerous biological properties, highlighting its immunomodulatory action. Here, we assayed the effects of propolis on the maturation and function of human DCs. DCs were generated from human monocytes and incubated with propolis and LPS. NF-κB and cytokines production were determined by ELISA. microRNA's expression was analysed by RT-qPCR and cell markers detection by flow cytometry. Colony-forming units were obtained to assess the bactericidal activity of propolis-treated DCs. Propolis activated DCs in the presence of LPS, inducing NF-kB, TNF-α, IL-6 and IL-10 production. The inhibition of hsa-miR-148a and hsa-miR-148b abolished the inhibitory effects on HLA-DR and pro-inflammatory cytokines. The increased expression of hsa-miR-155 may be correlated to the increase in TLR-4 and CD86 expression, maintaining LPS-induced expression of HLA-DR and CD40. Such parameters may be involved in the increased bactericidal activity of DCs against Streptococcus mutans. Propolis modulated the maturation and function of DCs and may be useful in the initial steps of the immune response, providing a novel approach to the development of DC-based strategies and for the discovery of new immunomodulators. © 2016 Royal Pharmaceutical Society.

Impairment of regulatory capacity of CD4+CD25+ regulatory T cells mediated by dendritic cell polarization and hyperthyroidism in Graves' disease.

PubMed

Mao, Chaoming; Wang, Shu; Xiao, Yichuan; Xu, Jingwei; Jiang, Qian; Jin, Min; Jiang, Xiaohua; Guo, Hua; Ning, Guang; Zhang, Yanyun

2011-04-15

Graves' disease (GD) is one of the most common autoimmune diseases. The immune dysfunction in GD involves the generation of thyroid-stimulating hormone receptor (TSHR) autoantibodies that presumably arise consequent to interactions among dendritic cells (DCs), T cells, and regulatory T (Treg) cells. However, the immunological mechanisms of interactions between them that lead to the induction and regulation of this autoimmune disease are poorly defined. In this study, we investigated whether DCs are the main cause of the defective activity of Treg cells in GD patients. We found a significant decrease in the percentage of circulating CD4(+)CD25(+)FOXP3(+) Treg cells in untreated GD patients (uGD), which was negatively correlated with the concentration of TSHR autoantibodies. uGD-derived DCs were polarized to increase the number of plasmacytoid DCs (pDCs) and conferred the ability to abrogate the suppressive function of Treg cells through inducing apoptosis of CD4(+)CD25(+) Treg cells in an IFN-α-dependent manner, and elevated thyroid hormones further exacerbated the effect. The nucleotide UDP, which inhibits IFN-α secretion of pDCs through P2Y6 receptor signaling, restored the suppressive function of CD4(+)CD25(+) Treg cells. Collectively, uGD-derived DCs through pDC polarization and elevated thyroid hormones act in concert to impair the regulatory capacity of Treg cells, facilitating the production of TSHR autoantibodies in the pathogenesis of GD.

Bone marrow CD11b(+)F4/80(+) dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17.

PubMed

Zhang, Lingling; Fu, Jingjing; Sheng, Kangliang; Li, Ying; Song, Shanshan; Li, Peipei; Song, Shasha; Wang, Qingtong; Chen, Jingyu; Yu, Jianhua; Wei, Wei

2015-03-01

Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+) F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b(+)F4/80(+) DCs were measured in vitro. We found that BM CD11b(+)F4/80(+) DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b(+)F4/80(+) DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b(+)F4/80(+) DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b(+)F4/80(+) DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3(+) Treg cell expansion and suppressing Th17 function. The BM CD11b(+)F4/80(+) DCs might have a promising immunotherapeutic potential for autoimmune arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

Ultrasound sensitivity to changes in gout: a longitudinal study after two years of treatment.

PubMed

Peiteado, Diana; Villalba, Alejandro; Martín-Mola, Emilio; Balsa, Alejandro; De Miguel, Eugenio

2017-01-01

The goals of our study are to evaluate the urate-lowering therapy (ULT) effect on gout ultrasound (US) lesions and to explore US sensitivity to change in gout patients. Patients with chronic and symptomatic gout, confirmed by crystal identification, were prospectively included. Clinical and US assessments were performed at baseline and after 6, 12 and 24 months of ULT. The presence of double contour sign (DCS) and US- detectable tophi were assessed in the first metatarsophalangeals, the knees and patellar tendons. The mean and standard deviation were calculated for each parameter. The correlation between the clinical and US parameters was assessed by calculating Pearson's correlation coefficient. Sensitivity to change in the US examinations was assessed by estimating the smallest detectable difference (SDD). Twenty-three consecutive patients were included (96% men; mean age 59 ± 11 years). DCS and US tophi were detected in 73.9% and 91.3% of patients at baseline. A significant parallel improvement in the serum urate, clinical parameters and US lesions was found at the follow-up assessment. The SDD values for the global DCS and tophi were 0.52 and 0.69, respectively, which were smaller than the differences achieved over the course of the two years. A significant correlation between DCS and clinical parameters was observed (r =0.49, p=0.038). Ultrasound findings in gout patients show sensitivity to change and concurrent validity with uric acid reduction after ULT in gout patients. US can be a useful tool for gout tophus burden monitoring.

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

PubMed

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

2018-06-05

The aim of the present study was to investigate whether tumor-derived supernatants down-regulate the immune function of plasmacytoid dendritic cells (pDCs) in oral cancer and the potential molecular mechanisms of this effect. Immunohistochemistry (IHC) and flow cytometry were used to detect tumor-infiltrating and peripheral blood pDCs. MTS and flow cytometry were employed to evaluate the immune response of CD4 + T cells. Real-time PCR and ELISA assays were used to identify TLR-7 and TLR-9 expression, IFN-α production and tumor-secreted soluble cytokines. The proportion of pDCs (0.121%±0.043%) was significantly higher in Oral squamous cell carcinoma (OSCC) samples than in normal tissue (0.023%±0.016%) (P = 0.021). TLR9 mRNA was significantly lower in tumor-infiltrating pDCs and positively correlated to low IFN-α production (r = 0.956; P<0.01). The supernatant of oral cancer cells negatively regulated TLR9 mRNA expression and the subsequent IFN-α production of pDCs, which inhibited the immune response of CD4 + T cells. The neutralizing antibodies blocking assay showed that the specific inhibitory effect of pDC functionality was associated with the soluble fraction of the oral cancer environment, which is mainly mediated by IL-10 and TGF-β cooperation. Tumor-derived supernatants may impair the function of tumor-infiltrating pDCs, which subsequently decreases the immune response of CD4 + T cells in human oral cancer through TGF-β- and IL-10- dependent mechanisms. Careful manipulation of these impaired pDCs may help develop an important alternative immunotherapy for the treatment of oral cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Systematic assessment of duration and intensity of anodal transcranial direct current stimulation on primary motor cortex excitability.

PubMed

Tremblay, Sara; Larochelle-Brunet, Félix; Lafleur, Louis-Philippe; El Mouderrib, Sofia; Lepage, Jean-François; Théoret, Hugo

2016-09-01

Since the initial demonstration of linear effects of stimulation duration and intensity on the strength of after-effects associated with transcranial direct current stimulation (tDCS), few studies have systematically assessed how varying these parameters modulates corticospinal excitability. Therefore, the objective of this study was to systematically evaluate the effects of anodal tDCS on corticospinal excitability at two stimulation intensities (1 mA, 2 mA) and durations (10 min, 20 min), and determine the value of several variables in predicting response. Two groups of 20 individuals received, in two separate sessions, 1 and 2 mA anodal tDCS (left primary motor cortex (M1)-right supra-orbital montage) for either 10- or 20-min. Transcranial magnetic stimulation was delivered over left M1 and motor evoked potentials (MEPs) of the contralateral hand were recorded prior to tDCS and every 5 min for 20-min post-tDCS. The following predictive variables were evaluated: I-wave recruitment, stimulation intensity, baseline M1 excitability and inter-trial MEP variability. Results show that anodal tDCS failed to significantly modulate corticospinal excitability in all conditions. Furthermore, low response rates were identified across all parameter combinations. No baseline measure was significantly correlated with increases in MEP amplitude. However, a decrease in inter-trial MEP variability was linked to response to anodal tDCS. In conclusion, the present findings are consistent with recent reports showing high levels of inter-subject variability in the neurophysiological response to tDCS, which may partly explain inconsistent group results. Furthermore, the level of variability in the neurophysiological outcome measure, i.e. MEPs, appears to be related to response. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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.

The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging.

PubMed

Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria

2016-09-15

Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. Copyright © 2016 Elsevier B.V. All rights reserved.

HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.

PubMed

Reszka-Blanco, Natalia J; Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

2015-08-01

Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are rapidly activated during HIV-1 infection and are implicated in reducing the early viral load, as well as contributing to HIV-1-induced pathogenesis. However, most cell-free HIV-1 isolates are inefficient in activating human pDCs, and the mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly defined. In this study, we report that two genetically similar HIV-1 variants (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to produce alpha interferon (IFN-α). The highly pathogenic R3A efficiently activated pDCs to induce robust IFN-α production, while the less pathogenic R3B did not. The viral determinant for efficient pDC activation was mapped to the V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity. Furthermore, we showed that the Nef protein was also required for the activation of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated that Nef domains involved in CD4 downregulation were necessary for R3A to activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs, which contributes to pathogenesis. Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-α production, while most HIV-1 isolates are inefficient in activating pDCs. We have discovered that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings thus provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs and contributes to HIV-1 pathogenesis. These novel findings will be of great interest to those working on the roles of IFN and pDCs in HIV-1 pathogenesis in general and on the interaction of HIV-1 with pDCs in particular. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

PubMed Central

Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

2015-01-01

Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

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

PubMed

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

2016-09-01

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

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy.

PubMed

Gueguen, Claire; Bouley, Julien; Moussu, Hélène; Luce, Sonia; Duchateau, Magalie; Chamot-Rooke, Julia; Pallardy, Marc; Lombardi, Vincent; Nony, Emmanuel; Baron-Bodo, Véronique; Mascarell, Laurent; Moingeon, Philippe

2016-02-01

Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT). We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy. Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively. Markers differentially regulated in DC2s and DCreg cells were assessed by means of quantitative PCR in PBMCs from 80 patients with grass pollen allergy before and after 2 or 4 months of sublingual AIT in parallel with rhinoconjunctivitis symptom scores. We identified 20 and 26 new genes/proteins overexpressed in DC2s and DCreg cells, respectively. At an individual patient level, DC2-associated markers, such as CD141, GATA3, OX40 ligand, and receptor-interacting serine/threonine-protein kinase 4 (RIPK4), were downregulated after a 4-month sublingual AIT course concomitantly with an upregulation of DCreg cell-associated markers, including complement C1q subcomponent subunit A (C1QA), FcγRIIIA, ferritin light chain (FTL), and solute carrier organic anion transporter family member 2B1 (SLCO2B1), in the blood of clinical responders as opposed to nonresponders. Changes in such markers were better correlated with clinical benefit than alterations of allergen-specific CD4(+) T-cell or IgG responses. A combination of 5 markers predominantly expressed by blood DCs (ie, C1Q and CD141) or shared with lymphoid cells (ie, FcγRIIIA, GATA3, and RIPK4) reflecting changes in the balance of regulatory/proallergic responses in peripheral blood can be used as early as after 2 months to monitor the early onset of AIT efficacy. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Native cellulose nanofibrills induce immune tolerance in vitro by acting on dendritic cells

NASA Astrophysics Data System (ADS)

Tomić, Sergej; Kokol, Vanja; Mihajlović, Dušan; Mirčić, Aleksandar; Čolić, Miodrag

2016-08-01

Cellulose nanofibrills (CNFs) are attractive biocompatible, natural nanomaterials for wide biomedical applications. However, the immunological mechanisms of CNFs have been poorly investigated. Considering that dendritic cells (DCs) are the key immune regulatory cells in response to nanomaterials, our aim was to investigate the immunological mechanisms of CNFs in a model of DC-mediated immune response. We found that non-toxic concentrations of CNFs impaired the differentiation, and subsequent maturation of human monocyte-derived (mo)-DCs. In a co-culture with CD4+T cells, CNF-treated mo-DCs possessed a weaker allostimulatory and T helper (Th)1 and Th17 polarizing capacity, but a stronger capacity to induce Th2 cells and CD4+CD25hiFoxP3hi regulatory T cells. This correlated with an increased immunoglobulin-like transcript-4 and indolamine dioxygenase-1 expression by CNF-treated mo-DCs, following the partial internalization of CNFs and the accumulation of CD209 and actin bundles at the place of contacts with CNFs. Cumulatively, we showed that CNFs are able to induce an active immune tolerance by inducing tolerogenic DCs, which could be beneficial for the application of CNFs in wound healing and chronic inflammation therapies.

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.

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.

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

PubMed

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

2017-01-01

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

Bihemispheric tDCS enhances language recovery but does not alter BDNF levels in chronic aphasic patients.

PubMed

Marangolo, Paola; Fiori, Valentina; Gelfo, Francesca; Shofany, Jacob; Razzano, Carmelina; Caltagirone, Carlo; Angelucci, Francesco

2014-01-01

Several studies have shown that transcranial direct current stimulation (tDCS) is a useful tool to enhance language recovery in aphasia. It has also been suggested that modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) might be part of the mechanisms involved in tDCS effects on synaptic connectivity. However, all language studies have previously investigated the effects using unihemispheric stimulation. The purpose of the present study is to investigate the role of bihemispheric tDCS on language recovery and BDNF serum levels. Seven aphasic persons underwent an intensive language therapy in two different conditions: real bihemispheric stimulation over the left and right Broca's areas and a sham condition. After the stimulation, patients exibited a significant recovery in three language tasks (picture description, noun and verb naming) compared to the sham condition which persisted in the follow-up session. No significant differences were found in BDNF serum levels after tDCS stimulation and in the follow-up session. However, a significant positive correlation was present for the real stimulation condition between percent changes in BDNF levels and in the verb naming task. The data suggest that this novel approach may potentiate the recovery of language in chronic aphasia. They also emphasize the importance to further investigate the role of possible biomarkers associated with tDCS treatment response in language recovery.

Enhancing the mirror illusion with transcranial direct current stimulation.

PubMed

Jax, Steven A; Rosa-Leyra, Diana L; Coslett, H Branch

2015-05-01

Visual feedback has a strong impact on upper-extremity movement production. One compelling example of this phenomena is the mirror illusion (MI), which has been used as a treatment for post-stroke movement deficits (mirror therapy). Previous research indicates that the MI increases primary motor cortex excitability, and this change in excitability is strongly correlated with the mirror's effects on behavioral performance of neurologically-intact controls. Based on evidence that primary motor cortex excitability can also be increased using transcranial direct current stimulation (tDCS), we tested whether bilateral tDCS to the primary motor cortices (anode right-cathode left and anode left-cathode right) would modify the MI. We measured the MI using a previously-developed task in which participants make reaching movements with the unseen arm behind a mirror while viewing the reflection of the other arm. When an offset in the positions of the two limbs relative to the mirror is introduced, reaching errors of the unseen arm are biased by the reflected arm's position. We found that active tDCS in the anode right-cathode left montage increased the magnitude of the MI relative to sham tDCS and anode left-cathode right tDCS. We take these data as a promising indication that tDCS could improve the effect of mirror therapy in patients with hemiparesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of SURE, a four-item clinical checklist for detecting decisional conflict in patients.

PubMed

Ferron Parayre, Audrey; Labrecque, Michel; Rousseau, Michel; Turcotte, Stéphane; Légaré, France

2014-01-01

We sought to determine the psychometric properties of SURE, a 4-item checklist designed to screen for clinically significant decisional conflict in clinical practice. This study was a secondary analysis of a clustered randomized trial assessing the effect of DECISION+2, a 2-hour online tutorial followed by a 2-hour interactive workshop on shared decision making, on decisions to use antibiotics for acute respiratory infections. Patients completed SURE and also the Decisional Conflict Scale (DCS), as the gold standard, after consultation. We evaluated internal consistency of SURE using the Kuder-Richardson 20 coefficient (KR-20). We compared DCS and SURE scores using the Spearman correlation coefficient. We assessed sensitivity and specificity of SURE scores (cut-off score ≤3 out of 4) by identifying patients with and without clinically significant decisional conflict (DCS score >37.5 on a scale of 0-100). Of the 712 patients recruited during the trial, 654 completed both tools. SURE scores showed adequate internal consistency (KR-20 coefficient of 0.7). There was a significant correlation between DCS and SURE scores (Spearman's ρ = -0.45, P < 0.0001). The prevalence of clinically significant decisional conflict as estimated by the DCS was 5.2% (95% CI 3.7-7.3). Sensitivity and specificity of SURE ≤3 were 94.1% (95% CI 78.9-99.0) and 89.8% (95% CI 87.1-92.0), respectively. SURE shows adequate psychometric properties in a primary care population with a low prevalence of clinically significant decisional conflict. SURE has the potential to be a useful screening tool for practitioners, responding to the growing need for detecting clinically significant decisional conflict in patients.

Activation of the DLPFC Reveals an Asymmetric Effect in Risky Decision Making: Evidence from a tDCS Study

PubMed Central

Huang, Daqiang; Chen, Shu; Wang, Siqi; Shi, Jinchuan; Ye, Hang; Luo, Jun; Zheng, Haoli

2017-01-01

The phenomenon of loss aversion (the tendency for losses to have a greater impact than comparable gains) has long been observed in daily life. Neurocognitive studies and brain imaging studies have shed light on the correlation between the phenomenon of loss aversion and the brain region of the prefrontal cortex. Recent brain stimulation studies using bilateral transcranial magnetic stimulation or transcranial direct current stimulation (tDCS) have obtained various results showing the causal relationship between brain regions and decision making. With the goal of studying whether unilateral stimulation can change participants’ risky decision making in the frames of gains and losses, we applied different polarities of tDCS over the regions of the right or left prefrontal cortex. We also designed a risk measurement table (Multiple Price List) to reflect the participants’ attitudes toward risky decision making via the crossover point including the frames of gains and losses. The results of our experiment indicated that the participants tended to be more risk averse in the gain frame after receiving left anodal tDCS and more risk seeking in the loss frame after receiving right cathodal tDCS, which was consistent with the hypothesis that the process of risky decision making was correlated with the interaction of multiple systems in the brain. Our conclusion revealed an asymmetric effect of right/left DLPFC when the participants faced gains and losses, which partially provided the neural evidence and a feasible paradigm to help better understand risky decision making and loss aversion. The current study can not only expand the traditional understanding of the behavioral preferences of humans in economics but also accommodate empirical observations of behavioral economists on the preferences of humans. PMID:28174549

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.

Monte Carlo simulation of near-infrared light propagation in realistic adult head models with hair follicles

NASA Astrophysics Data System (ADS)

Pan, Boan; Fang, Xiang; Liu, Weichao; Li, Nanxi; Zhao, Ke; Li, Ting

2018-02-01

Near infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) has been used to measure brain activation, which are clinically important. Monte Carlo simulation has been applied to the near infrared light propagation model in biological tissue, and has the function of predicting diffusion and brain activation. However, previous studies have rarely considered hair and hair follicles as a contributing factor. Here, we attempt to use MCVM (Monte Carlo simulation based on 3D voxelized media) to examine light transmission, absorption, fluence, spatial sensitivity distribution (SSD) and brain activation judgement in the presence or absence of the hair follicles. The data in this study is a series of high-resolution cryosectional color photograph of a standing Chinse male adult. We found that the number of photons transmitted under the scalp decreases dramatically and the photons exported to detector is also decreasing, as the density of hair follicles increases. If there is no hair follicle, the above data increase and has the maximum value. Meanwhile, the light distribution and brain activation have a stable change along with the change of hair follicles density. The findings indicated hair follicles make influence of NIRS in light distribution and brain activation judgement.

Intercomparison of Open-Path Trace Gas Measurements with Two Dual Frequency Comb Spectrometers

PubMed Central

Waxman, Eleanor M.; Cossel, Kevin C.; Truong, Gar-Wing; Giorgetta, Fabrizio R.; Swann, William C.; Coburn, Sean; Wright, Robert J.; Rieker, Gregory B.; Coddington, Ian; Newbury, Nathan R.

2017-01-01

We present the first quantitative intercomparison between two open-path dual comb spectroscopy (DCS) instruments which were operated across adjacent 2-km open-air paths over a two-week period. We used DCS to measure the atmospheric absorption spectrum in the near infrared from 6021 to 6388 cm−1 (1565 to 1661 nm), corresponding to a 367 cm−1 bandwidth, at 0.0067 cm−1 sample spacing. The measured absorption spectra agree with each other to within 5×10−4 without any external calibration of either instrument. The absorption spectra are fit to retrieve concentrations for carbon dioxide (CO2), methane (CH4), water (H2O), and deuterated water (HDO). The retrieved dry mole fractions agree to 0.14% (0.57 ppm) for CO2, 0.35% (7 ppb) for CH4, and 0.40% (36 ppm) for H2O over the two-week measurement campaign, which included 23 °C outdoor temperature variations and periods of strong atmospheric turbulence. This agreement is at least an order of magnitude better than conventional active-source open-path instrument intercomparisons and is particularly relevant to future regional flux measurements as it allows accurate comparisons of open-path DCS data across locations and time. We additionally compare the open-path DCS retrievals to a WMO-calibrated cavity ringdown point sensor located along the path with good agreement. Short-term and long-term differences between the two systems are attributed, respectively, to spatial sampling discrepancies and to inaccuracies in the current spectral database used to fit the DCS data. Finally, the two-week measurement campaign yields diurnal cycles of CO2 and CH4 that are consistent with the presence of local sources of CO2 and absence of local sources of CH4. PMID:29276547

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.

2-Year Outcomes of High Bleeding Risk Patients After Polymer-Free Drug-Coated Stents.

PubMed

Garot, Philippe; Morice, Marie-Claude; Tresukosol, Damras; Pocock, Stuart J; Meredith, Ian T; Abizaid, Alexandre; Carrié, Didier; Naber, Christoph; Iñiguez, Andres; Talwar, Suneel; Menown, Ian B A; Christiansen, Evald H; Gregson, John; Copt, Samuel; Hovasse, Thomas; Lurz, Philipp; Maillard, Luc; Krackhardt, Florian; Ong, Paul; Byrne, Jonathan; Redwood, Simon; Windhövel, Ute; Greene, Samantha; Stoll, Hans-Peter; Urban, Philip

2017-01-17

A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding. This study analyzed 2-year outcomes to determine whether these benefits are maintained. In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization. At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS. Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Transcranial direct current stimulation over the parietal cortex alters bias in item and source memory tasks.

PubMed

Pergolizzi, Denise; Chua, Elizabeth F

2016-10-01

Neuroimaging data have shown that activity in the lateral posterior parietal cortex (PPC) correlates with item recognition and source recollection, but there is considerable debate about its specific contributions. Performance on both item and source memory tasks were compared between participants who were given bilateral transcranial direct current stimulation (tDCS) over the parietal cortex to those given prefrontal or sham tDCS. The parietal tDCS group, but not the prefrontal group, showed decreased false recognition, and less bias in item and source discrimination tasks compared to sham stimulation. These results are consistent with a causal role of the PPC in item and source memory retrieval, likely based on attentional and decision-making biases. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2011-07-11

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

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

PubMed Central

2014-01-01

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

Differential Recruitment of Dendritic Cells Subsets to Lymph Nodes Correlates with a Protective or Permissive T-Cell Response during Leishmania (Viannia) Braziliensis or Leishmania (Leishmania) Amazonensis Infection.

PubMed

Carvalho, A K; Carvalho, K; Passero, L F D; Sousa, M G T; da Matta, V L R; Gomes, C M C; Corbett, C E P; Kallas, G E; Silveira, F T; Laurenti, M D

2016-01-01

Leishmania (L.) amazonensis (La) and L. (V.) braziliensis (Lb) are responsible for a large clinical and immunopathological spectrum in human disease; while La may be responsible for anergic disease, Lb infection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by these Leishmania species, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course of La and Lb infection in BALB/c mice. Our results demonstrated a high involvement of DCs in La infection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely, Lb infection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4(+) T-cells was observed in Lb infection. Interleukin- (IL-) 4- and IL-10-producing CD4(+)and CD8(+) T-cells were present in both La and Lb infection; however, interferon- (IFN-) γ-producing CD4(+)and CD8(+) T-cells were detected only in Lb infection. The results suggest that during Lb infection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrast La infection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.

Language mapping with navigated transcranial magnetic stimulation in pediatric and adult patients undergoing epilepsy surgery: Comparison with extraoperative direct cortical stimulation.

PubMed

Lehtinen, Henri; Mäkelä, Jyrki P; Mäkelä, Teemu; Lioumis, Pantelis; Metsähonkala, Liisa; Hokkanen, Laura; Wilenius, Juha; Gaily, Eija

2018-06-01

Navigated transcranial magnetic stimulation (nTMS) is becoming increasingly popular in noninvasive preoperative language mapping, as its results correlate well enough with those obtained by direct cortical stimulation (DCS) during awake surgery in adult patients with tumor. Reports in the context of epilepsy surgery or extraoperative DCS in adults are, however, sparse, and validation of nTMS with DCS in children is lacking. Furthermore, little is known about the risk of inducing epileptic seizures with nTMS in pediatric epilepsy patients. We provide the largest validation study to date in an epilepsy surgery population. We compared language mapping with nTMS and extraoperative DCS in 20 epilepsy surgery patients (age range 9-32 years; 14 children and adolescents). In comparison with DCS, sensitivity of nTMS was 68%, specificity 76%, positive predictive value 27%, and negative predictive value 95%. Age, location of ictal-onset zone near or within DCS-mapped language areas or severity of cognitive deficits had no significant effect on these values. None of our patients had seizures during nTMS. Our study suggests that nTMS language mapping is clinically useful and safe in epilepsy surgery patients, including school-aged children and patients with extensive cognitive dysfunction. Similar to in tumor surgery, mapping results in the frontal region are most reliable. False negative findings may be slightly more likely in epilepsy than in tumor surgery patients. Mapping results should always be verified by other methods in individual patients.

Inhibition of the Differentiation of Monocyte-Derived Dendritic Cells by Human Gingival Fibroblasts

PubMed Central

Séguier, Sylvie; Tartour, Eric; Guérin, Coralie; Couty, Ludovic; Lemitre, Mathilde; Lallement, Laetitia; Folliguet, Marysette; Naderi, Samah El; Terme, Magali; Badoual, Cécile; Lafont, Antoine; Coulomb, Bernard

2013-01-01

We investigated whether gingival fibroblasts (GFs) can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs) and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM) from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05) inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism. PMID:23936476

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.

Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

PubMed Central

Tomić, Sergej; Đokić, Jelena; Vasilijić, Saša; Ogrinc, Nina; Rudolf, Rebeka; Pelicon, Primož; Vučević, Dragana; Milosavljević, Petar; Janković, Srđa; Anžel, Ivan; Rajković, Jelena; Rupnik, Marjan Slak; Friedrich, Bernd; Čolić, Miodrag

2014-01-01

Gold nanoparticles (GNPs) are claimed as outstanding biomedical tools for cancer diagnostics and photo-thermal therapy, but without enough evidence on their potentially adverse immunological effects. Using a model of human dendritic cells (DCs), we showed that 10 nm- and 50 nm-sized GNPs (GNP10 and GNP50, respectively) were internalized predominantly via dynamin-dependent mechanisms, and they both impaired LPS-induced maturation and allostimulatory capacity of DCs, although the effect of GNP10 was more prominent. However, GNP10 inhibited LPS-induced production of IL-12p70 by DCs, and potentiated their Th2 polarization capacity, while GNP50 promoted Th17 polarization. Such effects of GNP10 correlated with a stronger inhibition of LPS-induced changes in Ca2+ oscillations, their higher number per DC, and more frequent extra-endosomal localization, as judged by live-cell imaging, proton, and electron microscopy, respectively. Even when released from heat-killed necrotic HEp-2 cells, GNP10 inhibited the necrotic tumor cell-induced maturation and functions of DCs, potentiated their Th2/Th17 polarization capacity, and thus, impaired the DCs' capacity to induce T cell-mediated anti-tumor cytotoxicity in vitro. Therefore, GNP10 could potentially induce more adverse DC-mediated immunological effects, compared to GNP50. PMID:24802102

Two-dimensional fluorescence-detected coherent spectroscopy with absolute phasing by confocal imaging of a dynamic grating and 27-step phase-cycling

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

De, Arijit K., E-mail: akde@lbl.gov; Fleming, Graham R., E-mail: grfleming@lbl.gov; Department of Chemistry, University of California at Berkeley, Berkeley, California 94702

2014-05-21

We present a novel experimental scheme for two-dimensional fluorescence-detected coherent spectroscopy (2D-FDCS) using a non-collinear beam geometry with the aid of “confocal imaging” of dynamic (population) grating and 27-step phase-cycling to extract the signal. This arrangement obviates the need for distinct experimental designs for previously developed transmission detected non-collinear two-dimensional coherent spectroscopy (2D-CS) and collinear 2D-FDCS. We also describe a novel method for absolute phasing of the 2D spectrum. We apply this method to record 2D spectra of a fluorescent dye in solution at room temperature and observe “spectral diffusion.”.

Coregulatory Interactions among CD8α Dendritic Cells, the Latency-Associated Transcript, and Programmed Death 1 Contribute to Higher Levels of Herpes Simplex Virus 1 Latency

PubMed Central

Mott, Kevin R.; Allen, Sariah J.; Zandian, Mandana

2014-01-01

ABSTRACT The latency-associated transcript (LAT) of herpes simplex virus 1 (HSV-1), CD8α+ dendritic cells (DCs), and programmed death 1 (PD-1) have all been implicated in the HSV-1 latency-reactivation cycle. It is not known, however, whether an interaction between LAT and CD8α+ DCs regulates latency and T-cell exhaustion. To address this question, we used LAT-expressing [LAT(+)] and LAT-negative [LAT(−)] viruses. Depletion of DCs in mice ocularly infected with LAT(+) virus resulted in a reduction in the number of T cells expressing PD-1 in the trigeminal ganglia (TG), whereas depletion of DCs in mice similarly infected with LAT(−) virus did not alter PD-1 expression. CD8α+ DCs, but not CD4+ DCs, infected with LAT(+) virus had higher levels of ICP0, ICP4, thymidine kinase (TK), and PD-1 ligand 1 (PD-L1) transcripts than those infected with LAT(−) virus. Coculture of infected bone marrow (BM)-derived DCs from wild-type (WT) mice, but not infected DCs from CD8α−/− mice, with WT naive T cells contributed to an increase in PD-1 expression. Transfer of bone marrow from WT mice but not CD8α−/− mice to recipient Rag1−/− mice increased the number of latent viral genomes in reconstituted mice infected with the LAT(+) virus. Collectively, these data indicated that a reduction in latency correlated with a decline in the levels of CD8α+ DCs and PD-1 expression. In summary, our results demonstrate an interaction among LAT, PD-1, and CD11c CD8α+ cells that regulates latency in the TG of HSV-1-infected mice. IMPORTANCE Very little is known regarding the interrelationship of LAT, PD-1, and CD8α+ DCs and how such interactions might contribute to relative numbers of latent viral genomes. We show here that (i) in both in vivo and in vitro studies, deficiency of CD8α+ DCs significantly reduced T-cell exhaustion in the presence of LAT(+) virus but not LAT(−) virus; (ii) HSV-1 infectivity was significantly lower in LAT(−)-infected DCs than in their LAT(+)-infected counterparts; and (iii) adoptive transfer of bone marrow (BM) from WT but not CD8α−/− mice to recipient Rag1−/− mice restored latency to the level in WT mice following infection with LAT(+) virus. These studies point to a key role for CD8α+ DCs in T-cell exhaustion in the presence of LAT, which leads to larger numbers of latent viral genomes. Thus, altering this negative function of CD8α+ DCs can potentially be used to generate a more effective vaccine against HSV infection. PMID:24672046

Cytokine-Mediated Loss of Blood Dendritic Cells During Epstein-Barr Virus-Associated Acute Infectious Mononucleosis: Implication for Immune Dysregulation.

PubMed

Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

2015-12-15

Acute infectious mononucleosis (IM) is associated with altered expression of inflammatory cytokines and disturbed T-cell homeostasis, however, the precise mechanism of this immune dysregulation remains unresolved. In the current study we demonstrated a significant loss of circulating myeloid and plasmacytoid dendritic cells (DCs) during acute IM, a loss correlated with the severity of clinical symptoms. In vitro exposure of blood DCs to acute IM plasma resulted in loss of plasmacytoid DCs, and further studies with individual cytokines showed that exposure to interleukin 10 could replicate this effect. Our data provide important mechanistic insight into dysregulated immune homeostasis during acute IM. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Study of Hind Limb Tissue Gas Phase Formation in Response to Suspended Adynamia and Hypokinesia

NASA Technical Reports Server (NTRS)

Butler, Bruce D.

1996-01-01

The purpose of this study was to investigate the hypothesis that reduced joint/muscle activity (hypo kinesia) as well as reduced or null loading of limbs (adynamia) in gravity would result in reduced decompression-induced gas phase and symptoms of decompression sickness (DCS). Finding a correlation between the two phenomena would correspond to the proposed reduction in tissue gas phase formation in astronauts undergoing decompression during extravehicular activity (EVA) in microgravity. The observation may further explain the reported low incidence of DCS in space.

Intercomparison of open-path trace gas measurements with two dual-frequency-comb spectrometers

DOE PAGES

Waxman, Eleanor M.; Cossel, Kevin C.; Truong, Gar-Wing; ...

2017-09-11

We present the first quantitative intercomparison between two open-path dual-comb spectroscopy (DCS) instruments which were operated across adjacent 2 km open-air paths over a 2-week period. We used DCS to measure the atmospheric absorption spectrum in the near infrared from 6023 to 6376 cm −1 (1568 to 1660 nm), corresponding to a 355 cm −1 bandwidth, at 0.0067 cm −1 sample spacing. The measured absorption spectra agree with each other to within 5 × 10 −4 in absorbance without any external calibration of either instrument. The absorption spectra are fit to retrieve path-integrated concentrations for carbon dioxide (CO 2), methane (CH 4), water (H 2O), and deuteratedmore » water (HDO). The retrieved dry mole fractions agree to 0.14 % (0.57 ppm) for CO 2, 0.35 % (7 ppb) for CH 4, and 0.40 % (36 ppm) for H 2O at  ∼  30 s integration time over the 2-week measurement campaign, which included 24 °C outdoor temperature variations and periods of strong atmospheric turbulence. This agreement is at least an order of magnitude better than conventional active-source open-path instrument intercomparisons and is particularly relevant to future regional flux measurements as it allows accurate comparisons of open-path DCS data across locations and time. We additionally compare the open-path DCS retrievals to a World Meteorological Organization (WMO)-calibrated cavity ring-down point sensor located along the path with good agreement. Short-term and long-term differences between the open-path DCS and point sensor are attributed, respectively, to spatial sampling discrepancies and to inaccuracies in the current spectral database used to fit the DCS data. Finally, the 2-week measurement campaign yields diurnal cycles of CO 2 and CH 4 that are consistent with the presence of local sources of CO 2 and absence of local sources of CH 4.« less

Intercomparison of open-path trace gas measurements with two dual-frequency-comb spectrometers

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

Waxman, Eleanor M.; Cossel, Kevin C.; Truong, Gar-Wing

We present the first quantitative intercomparison between two open-path dual-comb spectroscopy (DCS) instruments which were operated across adjacent 2 km open-air paths over a 2-week period. We used DCS to measure the atmospheric absorption spectrum in the near infrared from 6023 to 6376 cm −1 (1568 to 1660 nm), corresponding to a 355 cm −1 bandwidth, at 0.0067 cm −1 sample spacing. The measured absorption spectra agree with each other to within 5 × 10 −4 in absorbance without any external calibration of either instrument. The absorption spectra are fit to retrieve path-integrated concentrations for carbon dioxide (CO 2), methane (CH 4), water (H 2O), and deuteratedmore » water (HDO). The retrieved dry mole fractions agree to 0.14 % (0.57 ppm) for CO 2, 0.35 % (7 ppb) for CH 4, and 0.40 % (36 ppm) for H 2O at  ∼  30 s integration time over the 2-week measurement campaign, which included 24 °C outdoor temperature variations and periods of strong atmospheric turbulence. This agreement is at least an order of magnitude better than conventional active-source open-path instrument intercomparisons and is particularly relevant to future regional flux measurements as it allows accurate comparisons of open-path DCS data across locations and time. We additionally compare the open-path DCS retrievals to a World Meteorological Organization (WMO)-calibrated cavity ring-down point sensor located along the path with good agreement. Short-term and long-term differences between the open-path DCS and point sensor are attributed, respectively, to spatial sampling discrepancies and to inaccuracies in the current spectral database used to fit the DCS data. Finally, the 2-week measurement campaign yields diurnal cycles of CO 2 and CH 4 that are consistent with the presence of local sources of CO 2 and absence of local sources of CH 4.« less

Decision-Making Quality in Parents Considering Adenotonsillectomy or Tympanostomy Tube Insertion for Their Children.

PubMed

Hong, Paul; Maguire, Erin; Purcell, Mary; Ritchie, Krista C; Chorney, Jill

2017-03-01

Shared decision making is a process in which clinicians and patients make health care decisions in a collaborative manner using the most up-to-date evidence, while considering patient values and preferences. Shared decision making is thought to have a positive influence on the decision-making process in medicine. To describe the level of decisional conflict and decisional regret experienced by parents considering surgery for their children and to determine relations among decisional conflict, decisional regret, and shared decision making. A prospective cohort study was conducted at an academic pediatric otolaryngology clinic. Participants included 126 parents of children younger than 6 years who underwent consultation for adenotonsillectomy or tympanostomy tube insertion. Parent participants completed the Shared Decision Making Questionnaire-Parent version, Decisional Conflict Scale (DCS), and Decisional Regret Scale (DRS). Surgeons completed the Shared Decision Making Questionnaire-Physician version. This study included 126 parents; 102 women (mean [SD] age, 33.2 [5.1] years) and 24 men (mean [SD] age, 35.6 [6.3] years). Overall, 34 parents (26%) reported clinically significant decisional conflict. Only 1 parent experienced moderate to strong decisional regret; 28 parents (43.7%) had mild decisional regret. Both parent and physician ratings of shared decision making were significantly negatively correlated with total DCS scores. Parent SDM-Q-9 and total DCS scores were significantly negatively correlated (rs[118] = -0.582; P < .001). Similarly, physician SDM-Q-Doc and total DCS scores were also significantly negatively correlated (rs[118] = -0.221; P = .04). Only parent ratings of shared decision making were significantly negatively correlated with total DRS scores (rs[63] = -0.254; P = .045). Those parents with clinically significant decisional conflict had significantly higher DRS scores (P = .02). Many parents experienced significant decisional conflict when making decisions about their child's elective surgical treatment. Parents who perceived themselves as being more involved in the decision-making process reported less decisional conflict and decisional regret. Future research should explore the influence of decision quality on health outcomes and develop methods to improve shared decision making.

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.

Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity

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

Hunter, Michael A.; Coffman, Brian A.; Gasparovic, Charles

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain's neural architecture, from the micro to macro scales, have yet to be investigated. In this paper, using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ( 1H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-statemore » networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. 1H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal–parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia ( p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. Finally, the observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders.« less

Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity

DOE PAGES

Hunter, Michael A.; Coffman, Brian A.; Gasparovic, Charles; ...

2014-10-12

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain's neural architecture, from the micro to macro scales, have yet to be investigated. In this paper, using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ( 1H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-statemore » networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. 1H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal–parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia ( p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. Finally, the observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders.« less

The Facilitative Effect of Transcranial Direct Current Stimulation on Visuospatial Working Memory in Patients with Diabetic Polyneuropathy: A Pre–post Sham-Controlled Study

PubMed Central

Wu, Yi-Jen; Tseng, Philip; Huang, Han-Wei; Hu, Jon-Fan; Juan, Chi-Hung; Hsu, Kuei-Sen; Lin, Chou-Ching

2016-01-01

Diabetes mellitus can lead to diabetic polyneuropathy (DPN) and cognitive deficits that manifest as peripheral and central neuropathy, respectively. In this study we investigated the relationship between visuospatial working memory (VSWM) capacity and DPN severity, and attempted to improve VSWM in DPN patients via the use of transcranial direct current stimulation (tDCS). Sixteen DPN patients and 16 age- and education-matched healthy control subjects received Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and Montreal Cognitive Assessment (MOCA) for baseline cognitive assessment. A forward- and backward-recall computerized Corsi block tapping task (CBT), both with and without a concurrent motor interference task was used to measure VSWM capacity. Each DPN patient underwent a pre-treatment CBT, followed by tDCS or sham treatment, then a post-treatment CBT on two separate days. We found that although patients with severe DPN (Dyck’s grade 2a or 2b) showed comparable general intelligence scores on WAIS-IV as their age- and education-matched healthy counterparts, they nonetheless showed mild cognitive impairment (MCI) on MOCA and working memory deficit on digit-span test of WAIS-IV. Furthermore, patients’ peripheral nerve conduction velocity (NCV) was positively correlated with their VSWM span in the most difficult CBT condition that involved backward-recall with motor interference such that patients with worse NCV also had lower VSWM span. Most importantly, anodal tDCS over the right DLPFC was able to improve low-performing patients’ VSWM span to be on par with the high-performers, thereby eliminating the correlation between NCV and VSWM. In summary, these findings suggest that (1) MCI and severe peripheral neuropathy can coexist with unequal severity in diabetic patients, (2) the positive correlation of VSWM and NCV suggests a link between peripheral and central neuropathies, and (3) anodal tDCS over the right DLPFC can improve DPN patients’ VSWM, particularly for the low-performing patients. PMID:27733822

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

PubMed Central

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

2011-01-01

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

Maternal allergy is associated with surface-bound IgE on cord blood basophils.

PubMed

Matson, Adam P; Cloutier, Michelle M; Dhongade, Ashish; Puddington, Lynn; Rafti, Ektor

2013-09-01

The cell type(s) mediating the maternal influence on allergic disease in children remain unclear. We set out to define the relationship between maternal allergy and frequencies of cord blood (CB) basophils, and plasmacytoid dendritic cells (pDCs); to characterize surface-bound IgE and FcεRI expressions on these cells; and to investigate the association between maternal and CB serum IgE levels with surface-bound IgE and FcεRI expressions. One hundred and three mother/infant dyads were recruited prenatally, and maternal allergic history was recorded. Maternal blood was collected prior to delivery, and CB was collected after birth. Flow cytometry was used to identify CB basophils and pDCs and to determine surface-bound IgE and FcεRI expressions. Frequencies of CB basophils and pDCs were low and not related to maternal history of allergy. Percentages of CB basophils with surface-bound IgE were significantly higher in infants of allergic mothers compared with infants of non-allergic mothers (median, 59.60% vs. 19.70%, p = 0.01). IgE on CB basophils correlated with CB IgE levels (r = 0.72, p < 0.0001), but not with maternal IgE levels (r = 0.26, p = 0.06). IgE on CB pDCs was low and not significantly associated with maternal or CB IgE levels. Similarly, FcεRI expression by CB basophils and pDCs was not significantly associated with maternal or CB IgE levels. Frequencies of CB basophils and pDCs are not influenced by maternal allergy. CB basophils and pDCs have surface-bound IgE and express FcεRI; however, only IgE on CB basophils appears influenced by maternal allergy. © 2013 The Authors. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.

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.

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.

Causal relationship between effective connectivity within the default mode network and mind-wandering regulation and facilitation.

PubMed

Kajimura, Shogo; Kochiyama, Takanori; Nakai, Ryusuke; Abe, Nobuhito; Nomura, Michio

2016-06-01

Transcranial direct current stimulation (tDCS) can modulate mind wandering, which is a shift in the contents of thought away from an ongoing task and/or from events in the external environment to self-generated thoughts and feelings. Although modulation of the mind-wandering propensity is thought to be associated with neural alterations of the lateral prefrontal cortex (LPFC) and regions in the default mode network (DMN), the precise neural mechanisms remain unknown. Using functional magnetic resonance imaging (fMRI), we investigated the causal relationships among tDCS (one electrode placed over the right IPL, which is a core region of the DMN, and another placed over the left LPFC), stimulation-induced directed connection alterations within the DMN, and modulation of the mind-wandering propensity. At the behavioral level, anodal tDCS on the right IPL (with cathodal tDCS on the left LPFC) reduced mind wandering compared to the reversed stimulation. At the neural level, the anodal tDCS on the right IPL decreased the afferent connections of the posterior cingulate cortex (PCC) from the right IPL and the medial prefrontal cortex (mPFC). Furthermore, mediation analysis revealed that the changes in the connections from the right IPL and mPFC correlated with the facilitation and inhibition of mind wandering, respectively. These effects are the result of the heterogeneous function of effective connectivity: the connection from the right IPL to the PCC inhibits mind wandering, whereas the connection from the mPFC to the PCC facilitates mind wandering. The present study is the first to demonstrate the neural mechanisms underlying tDCS modulation of mind-wandering propensity. Copyright © 2016 Elsevier Inc. All rights reserved.

Anodal transcranial direct current stimulation of the right anterior temporal lobe did not significantly affect verbal insight.

PubMed

Aihara, Takatsugu; Ogawa, Takeshi; Shimokawa, Takeaki; Yamashita, Okito

2017-01-01

Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight.

Alternate Reading Frame Protein (F Protein) of Hepatitis C Virus: Paradoxical Effects of Activation and Apoptosis on Human Dendritic Cells Lead to Stimulation of T Cells

PubMed Central

Samrat, Subodh Kumar; Li, Wen; Singh, Shakti; Kumar, Rakesh; Agrawal, Babita

2014-01-01

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected individuals due to lack, failure, or inefficiency of generated adaptive immune responses. In a minority of patients, acute infection is followed by viral clearance. The immune correlates of viral clearance are not clear yet but have been extensively investigated, suggesting that multispecific and multifunctional cellular immunity is involved. The generation of cellular immunity is highly dependent upon how antigen presenting cells (APCs) process and present various viral antigens. Various structural and non-structural HCV proteins derived from the open reading frame (ORF) have been implicated in modulation of dendritic cells (DCs) and APCs. Besides the major ORF proteins, the HCV core region also encodes an alternate reading frame protein (ARFP or F), whose function in viral pathogenesis is not clear. In the current studies, we sought to determine the role of HCV-derived ARFP in modulating dendritic cells and stimulation of T cell responses. Recombinant adenovirus vectors containing F or core protein derived from HCV (genotype 1a) were prepared and used to endogenously express these proteins in dendritic cells. We made an intriguing observation that endogenous expression of F protein in human DCs leads to contrasting effects on activation and apoptosis of DCs, allowing activated DCs to efficiently internalize apoptotic DCs. These in turn result in efficient ability of DCs to process and present antigen and to prime and stimulate F protein derived peptide-specific T cells from HCV-naive individuals. Taken together, our findings suggest important aspects of F protein in modulating DC function and stimulating T cell responses in humans. PMID:24475147

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

PubMed

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

2010-07-01

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

Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability.

PubMed

Inukai, Yasuto; Saito, Kei; Sasaki, Ryoki; Tsuiki, Shota; Miyaguchi, Shota; Kojima, Sho; Masaki, Mitsuhiro; Otsuru, Naofumi; Onishi, Hideaki

2016-01-01

Transcranial direct current stimulation (tDCS) is a representative non-invasive brain stimulation method (NIBS). tDCS increases cortical excitability not only in healthy individuals, but also in stroke patients where it contributes to motor function improvement. Recently, two additional types of transcranial electrical stimulation (tES) methods have been introduced that may also prove beneficial for stimulating cortical excitability; these are transcranial random noise stimulation (tRNS) and transcranial alternating current stimulation (tACS). However, comparison of tDCS with tRNS and tACS, in terms of efficacy in cortical excitability alteration, has not been reported thus far. We compared the efficacy of the three different tES methods for increasing cortical excitability using the same subject population and same current intensity. Fifteen healthy subjects participated in this study. Similar stimulation patterns (1.0 mA and 10 min) were used for the three conditions of stimulation (tDCS, tRNS, and tACS). Cortical excitability was explored via single-pulse TMS elicited motor evoked potentials (MEPs). Compared with pre-measurements, MEPs significantly increased with tDCS, tACS, and tRNS ( p < 0.05). Compared with sham measurements, significant increases in MEPs were also observed with tRNS and tACS ( p < 0.05), but not with tDCS. In addition, a significant correlation of the mean stimulation effect was observed between tRNS and tACS ( p = 0.019, r = 0.598). tRNS induced a significant increase in MEP compared with the Pre or Sham at all time points. tRNS resulted in the largest significant increase in MEPs. These findings suggest that tRNS is the most effective tES method and should be considered as part of a treatment plan for improving motor function in stroke patients.

A time-of-flight spectrometer for measuring inelastic to elastic differential cross-section ratios for electron-gas scattering

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

LeClair, L.R.; Trajmar, S.; Khakoo, M.A.

1996-05-01

We describe a crossed electron beam-atomic beam apparatus which utilizes a pulsed electron gun and field free drift tube to obtain time-of-flight (TOF) spectra of electrons scattered from atoms and molecules. This apparatus was constructed for the purpose of obtaining inelastic-to-elastic differential cross-section (DCS) ratios in the energy range extending from threshold to several eV above the threshold of the inelastic channel. The TOF approach eliminates the need for complicated calibration procedures required when using conventional electrostatic electron energy-loss spectroscopy (EELS) at these low energies. The characteristics of the apparatus will be given, along with representative TOF spectra from carbonmore » monoxide. From those spectra we obtained DCS ratios at 90{degree} scattering angle for excitation of the {ital a}{sup 3}{Pi} state of CO, in the impact energy range of 6{endash}15 eV. These ratios were measured with uncertainties as small as {plus_minus}4{percent}, which represents a substantial improvement over previous measurements in this energy range. This demonstrates the feasibility of using the TOF technique to measure DCS ratios which in turn can serve as secondary standards to normalize other inelastic DCSs obtained from measurements with EELS. {copyright} {ital 1996 American Institute of Physics.}« less

Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants.

PubMed

Lin, Pei-Yi; Roche-Labarbe, Nadege; Dehaes, Mathieu; Carp, Stefan; Fenoglio, Angela; Barbieri, Beniamino; Hagan, Katherine; Grant, P Ellen; Franceschini, Maria Angela

2013-03-14

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO₂). Thus, measures of CMRO₂ are reflective of neuronal viability and provide critical diagnostic information, making CMRO₂ an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO₂) as a surrogate for cerebral oxygen consumption. However, SO₂ is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO₂ are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO₂ (CMRO₂i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

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

PubMed

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

2014-01-01

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

Rapid dendritic cell mobilization to the large intestinal epithelium is associated with resistance to Trichuris muris infection.

PubMed

Cruickshank, Sheena M; Deschoolmeester, Matthew L; Svensson, Marcus; Howell, Gareth; Bazakou, Aikaterini; Logunova, Larisa; Little, Matthew C; English, Nicholas; Mack, Matthias; Grencis, Richard K; Else, Kathryn J; Carding, Simon R

2009-03-01

The large intestine is a major site of infection and disease, yet little is known about how immunity is initiated within this site and the role of dendritic cells (DCs) in this process. We used the well-established model of Trichuris muris infection to investigate the innate response of colonic DCs in mice that are inherently resistant or susceptible to infection. One day postinfection, there was a significant increase in the number of immature colonic DCs in resistant but not susceptible mice. This increase was sustained at day 7 postinfection in resistant mice when the majority of the DCs were mature. There was no increase in DC numbers in susceptible mice until day 13 postinfection. In resistant mice, most colonic DCs were located in or adjacent to the epithelium postinfection. There were also marked differences in the expression of colonic epithelial chemokines in resistant mice and susceptible mice. Resistant mice had significantly increased levels of epithelium-derived CCL2, CCL3, CCL5, and CCL20 compared with susceptible mice. Furthermore, administering neutralizing CCL5 and CCL20 Abs to resistant mice prevented DC recruitment. This study provides clear evidence of differences in the kinetics of DC responses in hosts inherently resistant and susceptible to infection. DC responses in the colon correlate with resistance to infection. Differences in the production of DC chemotactic chemokines by colonic epithelial cells in response to infection in resistant vs susceptible mice may explain the different kinetics of the DC response.

Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4.

PubMed

Schaeffer, Evelyne; Flacher, Vincent; Papageorgiou, Vasiliki; Decossas, Marion; Fauny, Jean-Daniel; Krämer, Melanie; Mueller, Christopher G

2015-07-01

Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.

Dendritic cell modification of neutrophil responses to infection after burn injury.

PubMed

Bohannon, Julia; Cui, Weihua; Sherwood, Edward; Toliver-Kinsky, Tracy

2010-09-01

Burn patients are highly susceptible to infections due to increased exposure through wounds and impairments in a number of immune functions. Dendritic cells (DCs) are important in activation of numerous immune responses that are essential for the clearance of infections. We have found that prophylactic treatment of burn-injured mice with the DC growth factor FLT3 ligand (FL) significantly increases resistance to burn wound infections in a DC-dependent manner that is correlated closely with enhanced bacterial clearance. However, as DCs are not typically microbicidal, the mechanisms by which DC modulation enhances bacterial clearance are not known. Due to the rapid response of neutrophils to cutaneous wounds, and the reported interactions between DCs and neutrophils, we investigated the role of neutrophils in FL-mediated resistance to burn wound infection. This was examined both in vivo and in vitro through neutrophil depletion, supplementation of neutrophils, and assessment of neutrophil chemotaxis following FL treatment. To test the involvement of DCs, CD11c-diphtheria toxin receptor transgenic mice were used to deplete DCs during FL treatment. Studies revealed that neutrophils do play a critical role in FL-mediated resistance to a burn wound infection. Additionally, treatment with FL after a burn injury enhances neutrophil-mediated control of bacterial spread, neutrophil migratory capacity, and myeloperoxidase production in a DC-dependent manner. The results of this study provide new insight into immunological mechanisms that can offer protection against infection after burn injury.

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

PubMed

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

2014-11-01

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

Interleukin 1-beta (IL-1β) production by innate cells following TLR stimulation correlates with TB recurrence in ART-treated HIV infected patients

PubMed Central

Thobakgale, Christina; Naidoo, Kewreshini; McKinnon, Lyle R.; Werner, Lise; Samsunder, Natasha; Karim, Salim Abdool; Ndung’u, Thumbi; Altfeld, Marcus; Naidoo, Kogieleum

2016-01-01

Background Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV co-infection, since immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. Methods Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time points prior to TB recurrence were stimulated with ligands for Toll like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multi-color flow cytometry and intracellular cytokine staining was used to detect IL-1β, TNF-α, IL-12 and IP10 responses from monocytes and myeloid dendritic cells (mDCs). Results Elevated production of IL-1β from monocytes following TLR-2, TLR-4 and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs respectively). Conclusion Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB. PMID:27654812

Hemodynamic measurements in rat brain and human muscle using diffuse near-infrared absorption and correlation spectroscopies

NASA Astrophysics Data System (ADS)

Yu, Guoqiang; Durduran, Turgut; Furuya, D.; Lech, G.; Zhou, Chao; Chance, Britten; Greenberg, J. H.; Yodh, Arjun G.

2003-07-01

Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a patient with peripheral vascular disease (PVD) were found.

Optimal timing of pulse onset for language mapping with navigated repetitive transcranial magnetic stimulation.

PubMed

Krieg, Sandro M; Tarapore, Phiroz E; Picht, Thomas; Tanigawa, Noriko; Houde, John; Sollmann, Nico; Meyer, Bernhard; Vajkoczy, Peter; Berger, Mitchel S; Ringel, Florian; Nagarajan, Srikantan

2014-10-15

Within the primary motor cortex, navigated transcranial magnetic stimulation (nTMS) has been shown to yield maps strongly correlated with those generated by direct cortical stimulation (DCS). However, the stimulation parameters for repetitive nTMS (rTMS)-based language mapping are still being refined. For this purpose, the present study compares two rTMS protocols, which differ in the timing of pulse train onset relative to picture presentation onset during object naming. Results were the correlated with DCS language mapping during awake surgery. Thirty-two patients with left-sided perisylvian tumors were examined by rTMS prior to awake surgery. Twenty patients underwent rTMS pulse trains starting at 300 ms after picture presentation onset (delayed TMS), whereas another 12 patients received rTMS pulse trains starting at the picture presentation onset (ONSET TMS). These rTMS results were then evaluated for correlation with intraoperative DCS results as gold standard in terms of differential consistencies in receiver operating characteristics (ROC) statistics. Logistic regression analysis by protocols and brain regions were conducted. Within and around Broca's area, there was no difference in sensitivity (onset TMS: 100%, delayed TMS: 100%), negative predictive value (NPV) (onset TMS: 100%, delayed TMS: 100%), and positive predictive value (PPV) (onset TMS: 55%, delayed TMS: 54%) between the two protocols compared to DCS. However, specificity differed significantly (onset TMS: 67%, delayed TMS: 28%). In contrast, for posterior language regions, such as supramarginal gyrus, angular gyrus, and posterior superior temporal gyrus, early pulse train onset stimulation showed greater specificity (onset TMS: 92%, delayed TMS: 20%), NPV (onset TMS: 92%, delayed TMS: 57%) and PPV (onset TMS: 75%, delayed TMS: 30%) with comparable sensitivity (onset TMS: 75%, delayed TMS: 70%). Logistic regression analysis also confirmed the greater fit of the predictions by rTMS that had the pulse train onset coincident with the picture presentation onset when compared to the delayed stimulation. Analyses of differential disruption patterns of mapped cortical regions were further able to distinguish clusters of cortical regions standardly associated with semantic and pre-vocalization phonological networks proposed in various models of word production. Repetitive nTMS predictions by both protocols correlate well with DCS outcomes especially in Broca's region, particularly with regard to TMS negative predictions. With this study, we have demonstrated that rTMS stimulation onset coincident with picture presentation onset improves the accuracy of preoperative language maps, particularly within posterior language areas. Moreover, immediate and delayed pulse train onsets may have complementary disruption patterns that could differentially capture cortical regions causally necessary for semantic and pre-vocalization phonological networks. Published by Elsevier Inc.

Dynamic functional connectivity and its behavioral correlates beyond vigilance.

PubMed

Patanaik, Amiya; Tandi, Jesisca; Ong, Ju Lynn; Wang, Chenhao; Zhou, Juan; Chee, Michael W L

2018-04-25

Fluctuations in resting-state functional connectivity and global signal have been found to correspond with vigilance fluctuations, but their associations with other behavioral measures are unclear. We evaluated 52 healthy adolescents after a week of adequate sleep followed by five nights of sleep restriction to unmask inter-individual differences in cognition and mood. Resting state scans obtained at baseline only, analyzed using sliding window analysis, consistently yielded two polar dynamic functional connectivity states (DCSs) corresponding to previously reported 'low arousal' and 'high arousal' states. We found that the relative temporal preponderance of two dynamic connectivity states (DCS) in well-rested participants, indexed by a median split of participants, based on the relative time spent in these DCS, revealed highly significant group differences in vigilance at baseline and its decline following multiple nights of sleep restriction. Group differences in processing speed and working memory following manipulation but not at baseline suggest utility of DCS in predicting cognitive vulnerabilities unmasked by a stressor like sleep restriction. DCS temporal predominance was uninformative about mood and sleepiness speaking to specificity in its behavioral predictions. Global signal fluctuation provided information confined to vigilance. This appears to be related to head motion, which increases during periods of low arousal. Copyright © 2018. Published by Elsevier Inc.

The truth about lying: inhibition of the anterior prefrontal cortex improves deceptive behavior.

PubMed

Karim, Ahmed A; Schneider, Markus; Lotze, Martin; Veit, Ralf; Sauseng, Paul; Braun, Christoph; Birbaumer, Niels

2010-01-01

Recent neuroimaging studies have indicated a predominant role of the anterior prefrontal cortex (aPFC) in deception and moral cognition, yet the functional contribution of the aPFC to deceptive behavior remains unknown. We hypothesized that modulating the excitability of the aPFC by transcranial direct current stimulation (tDCS) could reveal its functional contribution in generating deceitful responses. Forty-four healthy volunteers participated in a thief role-play in which they were supposed to steal money and then to attend an interrogation with the Guilty Knowledge Test. During the interrogation, participants received cathodal, anodal, or sham tDCS. Remarkably, inhibition of the aPFC by cathodal tDCS did not lead to an impairment of deceptive behavior but rather to a significant improvement. This effect manifested in faster reaction times in telling lies, but not in telling the truth, a decrease in sympathetic skin-conductance response and feelings of guilt while deceiving the interrogator and a significantly higher lying quotient reflecting skillful lying. Increasing the excitability of the aPFC by anodal tDCS did not affect deceptive behavior, confirming the specificity of the stimulation polarity. These findings give causal support to recent correlative data obtained by functional magnetic resonance imaging studies indicating a pivotal role of the aPFC in deception.

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.

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.

Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study.

PubMed

Tepelus, Tudor C; Chiu, Gloria B; Huang, Jianyan; Huang, Ping; Sadda, SriniVas R; Irvine, John; Lee, Olivia L

2017-09-01

To evaluate corneal innervation and inflammatory cell infiltration using in vivo confocal microscopy (IVCM) and to correlate these findings with subjective symptoms of dry eye, as measured by the Ocular Surface Disease Index (OSDI) in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE). Central corneal images were prospectively captured from 10 age-matched healthy control eyes, 24 eyes with clinically diagnosed NSDE and 44 eyes with clinically diagnosed SSDE, using IVCM (HRT III RCM). Density, tortuosity and reflectivity of corneal nerves, presence of inflammatory dendritic cells (DCs) and OSDI scores were evaluated. Images obtained by IVCM from 78 eyes were analyzed. The density of nerve fibers was 1562 ± 996 μm/frame in the SSDE group, 2150 ± 1015 μm/frame in the NSDE group and 2725 ± 687 μm/frame in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of nerve fibers was decreased in the SSDE (P < 0.001) and the NSDE groups (P = 0.06), with increased nerve tortuosity and decreased reflectivity in both groups (both P < 0.05). The density of DCs was 71.65 ± 72.54 cells/mm 2 in the SSDE group, 40.33 ± 31.63 cells/mm 2 in the NSDE group and 27.53 ± 5.58 cells/mm 2 in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of DCs was increased in the SSDE (P < 0.001) and the NSDE groups (P = 0.07). Significant correlations were found between the nerve density and DC density (r = -0.57, P < 0.001), between the nerve density and OSDI scores (r = -0.91, P < 0.001) and between the nerve reflectivity and OSDI scores (r = -0.75, P < 0.001). The corneas of eyes affected with NSDE and SSDE are characterized by alterations in corneal innervation and infiltration of inflammatory DCs. Corneal nerve density and reflectivity are correlated with severity of subjective dry eye symptoms, as measured by OSDI score.

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

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

PubMed

Busch, David R; Lynch, Jennifer M; Winters, Madeline E; McCarthy, Ann L; Newland, John J; Ko, Tiffany; Cornaglia, Mary Anne; Radcliffe, Jerilynn; McDonough, Joseph M; Samuel, John; Matthews, Edward; Xiao, Rui; Yodh, Arjun G; Marcus, Carole L; Licht, Daniel J; Tapia, Ignacio E

2016-01-01

Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS. © 2016 Associated Professional Sleep Societies, LLC.

Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, vaccination, and protection using intranasally administered antigen-pulsed dendritic cells.

PubMed

Pham, Giang H; Iglesias, Bibiana V; Gosselin, Edmund J

2014-09-08

Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our studies using a Francisella tularensis (Ft) infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo targeting of iFt to FcγR on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. Increased protection correlated with increased iFt loading on the BMDC surface as a consequence of FcγR-targeting. However, the inhibitory FcγRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to FcγR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of FcγRIIB. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fc Receptor-Targeting of Immunogen as a Strategy for Enhanced Antigen Loading, Vaccination, and Protection Using Intranasally-Administered Antigen-Pulsed Dendritic Cells

PubMed Central

Pham, Giang H.; Iglesias, Bibiana V.; Gosselin, Edmund J.

2014-01-01

Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our studies using an F. tularensis (Ft) infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo targeting of iFt to FcγR on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. Increased protection correlated with increased iFt loading on the BMDC surface as a consequence of FcγR targeting. However, the inhibitory FcγRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to FcγR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of FcγRIIB. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer. PMID:25068496

Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae.

PubMed

Kumagai, Takanori; Koyama, Yusuke; Oda, Kosuke; Noda, Masafumi; Matoba, Yasuyuki; Sugiyama, Masanori

2010-03-01

In the present study, we successfully cloned a 21-kb DNA fragment containing a d-cycloserine (DCS) biosynthetic gene cluster from a DCS-producing Streptomyces lavendulae strain, ATCC 11924. The putative gene cluster consists of 10 open reading frames (ORFs), designated dcsA to dcsJ. This cluster includes two ORFs encoding D-alanyl-D-alanine ligase (dcsI) and a putative membrane protein (dcsJ) as the self-resistance determinants of the producer organism, indicated by our previous work. When the 10 ORFs were introduced into DCS-nonproducing Streptomyces lividans 66 as a heterologous host cell, the transformant acquired DCS productivity. This reveals that the introduced genes are responsible for the biosynthesis of DCS. As anticipated, the disruption of dcsG, seen in the DCS biosynthetic gene cluster, made it possible for the strain ATCC 11924 to lose its DCS production. We here propose the DCS biosynthetic pathway. First, L-serine is O acetylated by a dcsE-encoded enzyme homologous to homoserine O-acetyltransferase. Second, O-acetyl-L-serine accepts hydroxyurea via an O-acetylserine sulfhydrylase homolog (dcsD product) and forms O-ureido-L-serine. The hydroxyurea must be supplied by the catalysis of a dcsB-encoded arginase homolog using the L-arginine derivative, N(G)-hydroxy-L-arginine. The resulting O-ureido-L-serine is then racemized to O-ureido-D-serine by a homolog of diaminopimelate epimerase. Finally, O-ureido-D-serine is cyclized to form DCS with the release of ammonia and carbon dioxide. The cyclization must be done by the dcsG or dcsH product, which belongs to the ATP-grasp fold family of protein.

Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage

PubMed Central

Kwiatek, Maciej; Gęca, Tomasz; Krzyżanowski, Arkadiusz; Malec, Agnieszka; Kwaśniewska, Anna

2015-01-01

The development of pregnancy is possible due to initiation of immune response in the body of the mother resulting in immune tolerance. Miscarriage may be caused by the impaired maternal immune response to paternal alloantigens located on the surface of trophoblast and fetal cells. The aim of the study was to compare the population of circulating dendritic cells (DCs) and CD4+CD25+Foxp3+ regulatory T cells (TREGs) in the first trimester of a normal pregnancy and in women with recurrent miscarriage and an attempt to determine the relationship between these cells and the role they may play in human reproductive failures. The study was conducted in a group of 33 first trimester pregnant women with recurrent miscarriage and in a group of 20 healthy pregnant women in the first trimester of normal pregnancy. Among mononuclear cells isolated from peripheral blood, the populations of DCs and TREGs were assessed by flow cytometry. The percentage of myeloid DCs and lymphoid DCs showed no significant difference between study and control group. Older maternal age and obesity significantly reduced the pool of circulating myeloid and lymphoid DCs (R=-0.39, p=0.02). In miscarriages the percentage of circulating TREGs was significantly lower compared to normal pregnancies (p=0.003). Among the analysed factors the percentage of TREGs was the most sensitive and the most specific parameter which correlated with the pregnancy loss. The reduction in the population of circulating TREGs suggests immunoregulatory mechanisms disorder in a pregnancy complicated by miscarriage. PMID:25945787

Rapid Dendritic Cell Mobilisation to the Large Intestinal Epithelium is Associated with Resistance to Trichuris muris Infection

PubMed Central

Cruickshank, Sheena M; Deschoolmeester, Matthew L; Svensson, Marcus; Howell, Gareth; Bazakou, Aikaterini; Logunova, Larisa; Little, Matthew C; English, Nicholas; Mack, Matthias; Grencis, Richard K; Else, Kathryn J; Carding, Simon R

2009-01-01

The large intestine is a major site of infection and disease yet little is known about how immunity is initiated within this site and the role of dendritic cells (DCs) in this process. We used the well-established model of Trichuris muris infection to investigate the innate response of colonic DCs in mice that are inherently resistant or susceptible to infection. One day post-infection, there was a significant increase in the number of immature colonic DCs in resistant but not susceptible mice. This increase was sustained at day 7 post-infection in resistant mice when the majority of the DCs were mature. There was no increase in DC numbers in susceptible mice until day 13 post-infection. In resistant mice, most colonic DCs were located in or adjacent to the epithelium post-infection. There were also marked differences in the expression of colonic epithelial chemokines in resistant mice and susceptible mice. Resistant mice had significantly increased levels of epithelium-derived CCL2, CCL3, CCL5 and CCL20 compared with susceptible mice. Furthermore, administering neutralizing CCL5 and CCL20 antibodies to resistant mice prevented DC recruitment. This study provides clear evidence of differences in the kinetics of DC responses in hosts inherently resistant and susceptible to infection. DC responses in the colon correlate with resistance to infection. Differences in the production of DC chemotactic chemokines by colonic epithelial cells in response to infection in resistant versus susceptible mice may explain the different kinetics of the DC response. PMID:19234202

Identification of immune factors regulating anti-tumor immunity using polymeric vaccines with multiple adjuvants

PubMed Central

Ali, Omar A.; Verbeke, Catia; Johnson, Chris; Sands, Warren; Lewin, Sarah A.; White, Des; Doherty, Edward; Dranoff, Glenn; Mooney, David J.

2014-01-01

The innate cellular and molecular components required to mediate effective vaccination against weak tumor-associated antigens remain unclear. In this study we utilized polymeric cancer vaccines incorporating different classes of adjuvants to induce tumor protection, in order to identify dendritic cell subsets and cytokines critical to this efficacy. Three-dimensional, porous polymer matrices loaded with tumor lysates and presenting distinct combinations of GM-CSF and various TLR agonists effected 70–90% prophylactic tumor protection in B16-F10 melanoma models. In aggressive, therapeutic B16 models, the vaccine systems incorporating GM-CSF in combination with P(I:C) or CpG-ODN induced the complete regression of solid tumors (≤40mm2) resulting in 33% long-term survival. Regression analysis revealed that the numbers of vaccine-resident CD8(+) DCs and plasmacytoid DCs, along with local IL-12, and G-CSF concentrations correlated strongly to vaccine efficacy regardless of adjuvant type. Further, vaccine studies in Batf3−/− mice revealed that CD8(+) DCs are required to effect tumor protection, as vaccines in these mice were deficient in cytotoxic T cell priming, and IL-12 induction in comparison to wild-type. These studies broadly demonstrate that three-dimensional polymeric vaccines provide a potent platform for prophylactic and therapeutic protection, and can be used as a tool to identify critical components of a desired immune response. Specifically, these results suggest that CD8(+) DCs, plasmacytoid DCs, IL-12, and G-CSF play important roles in priming effective anti-tumor responses with these vaccines. PMID:24480625

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

The effects of different rates of ascent on the incidence of altitude decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Waligora, James M.

1989-01-01

The effect of different rates of ascent on the incidence of altitude decompression sickness (DCS) was analyzed by a retrospective study on 14,123 man-flights involving direct ascent up to 38,000 ft altitude. The data were classified on the basis of altitude attained, denitrogenation at ground level, duration of stay at altitude, rest or exercise while at altitude, frequency of exercise at altitude, and ascent rates. This database was further divided on the basis of ascent rates into different groups from 1000 ft/min up to 53,000 ft/min. The database was analyzed using multiple correlation and regression methods, and the results of the analysis reveal that ascent rates influence the incidence of DCS in combination with the various factors mentioned above. Rate of ascent was not a significant predictor of DCS and showed a low, but significant multiple correlation (R=0.31) with the above factors. Further, the effects of rates below 2500 ft/min are significantly different from that of rates above 2500 ft/min on the incidence of symptoms (P=0.03) and forced descent (P=0.01). At rates above 2500 ft/min and up to 53,000 ft/min, the effects of ascent rates are not significantly different (P greater than 0.05) in the population examined while the effects of rates below 2500 ft/min are not clear.

TREM-2 serves as a negative immune regulator through Syk pathway in an IL-10 dependent manner in lung cancer

PubMed Central

Chen, Junjun; Xu, Weiyi; Yang, Guangdie; Bao, Zhang; Xia, Dajing; Lu, Guohua; Hu, Shuwen; Zhou, Jianying

2016-01-01

During infection, triggering receptor expressed on myeloid cells-2 (TREM-2) restrains dendritic cells (DCs) and macrophages (MΦs) phagocytosis, as well as reduces pro-inflammatory cytokines release through DNAX-activation protein 12 (DAP12) signaling. However, the role of TREM-2 signaling in cancer has never been elucidated. In the current study, we found that TREM-2 was up-regulated on peripheral blood monocytes in tumor-bearing host. More TREM-2+DCs were detected in the lung of 3LL tumor-bearing mice. On the other hand, the level of TREM-2 on pulmonary MΦs positively correlated with the pathological staging of lung cancer. However, surgical or chemotherapeutic reduction of tumor burden led to the obvious decline of TREM-2. In vitro, TREM-2 expression of bone marrow (BM)-derived DCs and MΦs was induced by conditional medium (CM) containing the supernatant of 3LL cells. TREM-2+DCs from CM and/or tumor-bearing mice held altered phenotypes (CD80LowCD86LowMHCIILow) and impaired functions, such as, reduced interleukin (IL)-12 secretion, increased IL-10 production, and weakened ovalbumin (OVA)-endocytic capacity; also developed potent inhibitory effect on T cell proliferation that could be partially reversed by TREM-2 blockage. Moreover, spleen tyrosine kinase (Syk) inhibitor restrained IL-10 production of TREM-2+DC. Remarkably, IL-10 neutralizing antibody and Syk inhibitor both lowered the suppressive potential of TREM-2+DCs in T cell proliferation. Also, adoptive transfer of this TREM-2+DCs accelerated the tumor growth rather than jeopardized survival in lung cancer-bearing mice. In conclusion, these results indicate that TREM-2 might act as a negative immuno-regulatory molecule through Syk pathway in an IL-10 dependent manner and partially predicts prognosis in lung cancer patients. PMID:27102437

Anodal transcranial direct current stimulation of the right anterior temporal lobe did not significantly affect verbal insight

PubMed Central

Ogawa, Takeshi; Shimokawa, Takeaki; Yamashita, Okito

2017-01-01

Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight. PMID:28902872

Vibrational excitation of triatomic molecules near the shape resonance region

NASA Astrophysics Data System (ADS)

Ishijima, Y.; Ohkawa, M.; Hoshino, M.; Campbell, L.; Brunger, M. J.; Tanaka, H.

2012-11-01

In this study we have measured angular distributions of differential cross sections (DCS) for vibrational excitation and superelastic scattering from vibrationally excited N2O. The results are analyzed and interpreted using the angular correlation theory by Read.

Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age.

PubMed

Agrawal, Sudhanshu; Ganguly, Sreerupa; Tran, Alexander; Sundaram, Padmaja; Agrawal, Anshu

2016-06-01

Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141(hi), GARP(+) DCs displayed enhanced capacity to induce T regulatory cells compared to CD141(lo) and GARP(-) DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141(hi), GARP(+) DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases.

Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age

PubMed Central

Agrawal, Sudhanshu; Ganguly, Sreerupa; Tran, Alexander; Sundaram, Padmaja; Agrawal, Anshu

2016-01-01

Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141hi, GARP+ DCs displayed enhanced capacity to induce T regulatory cells compared to CD141lo and GARP− DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141hi, GARP+ DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases. PMID:27244900

Privatization of Army Lodging

DTIC Science & Technology

2008-03-25

primary point person for this initiative is ASA for Installations and Environment (ASA- I& E ). 9 * There are 11 major commands, only 1 shown on...FM&C) DCS G-8 DCS G-8 ASA (I& E ) ASA (I& E ) ASA (M&RA) ASA (M&RA) DCS G-1 DCS G-1 CIO/ G-6 CIO/ G-6 DCS G-2 DCS G-2 DCS G-3 DCS G-3 DASDAS ACSIM/ IMCOM...Army Ch of Staff Army Figure 1 – Army Stakeholders in Policy Process18 The Office of the ASA-I& E has responsibility for policy development

Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen.

PubMed

Plantinga, Maud; Guilliams, Martin; Vanheerswynghels, Manon; Deswarte, Kim; Branco-Madeira, Filipe; Toussaint, Wendy; Vanhoutte, Leen; Neyt, Katrijn; Killeen, Nigel; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N

2013-02-21

Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung. Copyright © 2013 Elsevier Inc. All rights reserved.

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

The emerging role of ASC in dendritic cell metabolism during Chlamydia infection

PubMed Central

McKeithen, Danielle N.; Ryans, Khamia; Mu, Jing; Xie, Zhonglin; Simoneaux, Tankya; Blas-machado, Uriel; Eko, Francis O.; Black, Carolyn M.; Igietseme, Joseph U.; He, Qing

2017-01-01

Chlamydia trachomatis is a bacterial agent that causes sexually transmitted infections worldwide. The regulatory functions of dendritic cells (DCs) play a major role in protective immunity against Chlamydia infections. Here, we investigated the role of ASC in DCs metabolism and the regulation of DCs activation and function during Chlamydia infection. Following Chlamydia stimulation, maturation and antigen presenting functions were impaired in ASC-/- DCs compared to wild type (WT) DCs, in addition, ASC deficiency induced a tolerant phenotype in Chlamydia stimulated DCs. Using real-time extracellular flux analysis, we showed that activation in Chlamydia stimulated WT DCs is associated with a metabolic change in which mitochondrial oxidative phosphorylation (OXPHOS) is inhibited and the cells become committed to utilizing glucose through aerobic glycolysis for differentiation and antigen presenting functions. However, in ASC-/- DCs Chlamydia-induced metabolic change was prevented and there was a significant effect on mitochondrial morphology. The mitochondria of Chlamydia stimulated ASC-/- DCs had disrupted cristae compared to the normal narrow pleomorphic cristae found in stimulated WT DCs. In conclusion, our results suggest that Chlamydia-mediated activation of DCs is associated with a metabolic transition in which OXPHOS is inhibited, thereby dedicating the DCs to aerobic glycolysis, while ASC deficiency disrupts DCs function by inhibiting the reprogramming of DCs metabolism within the mitochondria, from glycolysis to electron transport chain. PMID:29216217

Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness

PubMed Central

Nakamura, Koyo; Kawabata, Hideaki

2015-01-01

Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions. PMID:26696865

Distinct Phenotype, Longitudinal Changes of Numbers and Cell-Associated Virus in Blood Dendritic Cells in SIV-Infected CD8-Lymphocyte Depleted Macaques

PubMed Central

Soulas, Caroline; Autissier, Patrick J.; Burdo, Tricia H.; Lifson, Jeffrey D.; Williams, Kenneth C.

2015-01-01

Loss of circulating CD123+ plasmacytoid dendritic cells (pDCs) during HIV infection is well established. However, changes of myeloid DCs (mDCs) are ambiguous since they are studied as a homogeneous CD11c+ population despite phenotypic and functional heterogeneity. Heterogeneity of CD11c+ mDCs in primates is poorly described in HIV and SIV infection. Using multiparametric flow cytometry, we monitored longitudinally cell number and cell-associated virus of CD123+ pDCs and non-overlapping subsets of CD1c+ and CD16+ mDCs in SIV-infected CD8-depleted rhesus macaques. The numbers of all three DC subsets were significantly decreased by 8 days post-infection. Whereas CD123+ pDCs were persistently depleted, numbers of CD1c+ and CD16+ mDCs rebounded. Numbers of CD1c+ mDCs significantly increased by 3 weeks post-infection while numbers of CD16+ mDCs remained closer to pre-infection levels. We found similar changes in the numbers of all three DC subsets in CD8 depleted animals as we found in animals that were SIV infected animals that were not CD8 lymphocyte depleted. CD16+ mDCs and CD123+ pDCs but not CD1c+ mDCs were significantly decreased terminally with AIDS. All DC subsets harbored SIV RNA as early as 8 days and then throughout infection. However, SIV DNA was only detected in CD123+ pDCs and only at 40 days post-infection consistent with SIV RNA, at least in mDCs, being surface-bound. Altogether our data demonstrate that SIV infection differently affects CD1c+ and CD16+ mDCs where CD16+ but not CD1c+ mDCs are depleted and might be differentially regulated in terminal AIDS. Finally, our data underline the importance of studying CD1c+ and CD16+ mDCs as discrete populations, and not as total CD11c+ mDCs. PMID:25915601

Human monocyte-derived dendritic cells exposed to microorganisms involved in hypersensitivity pneumonitis induce a Th1-polarized immune response.

PubMed

Bellanger, Anne-Pauline; Pallandre, Jean-René; Borg, Christophe; Loeffert, Sophie; Gbaguidi-Haore, Houssein; Millon, Laurence

2013-08-01

Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4(+) T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested.

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

PubMed

Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence

PubMed Central

Coallier, Émilie; Michelet, Thomas

2015-01-01

We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1. PMID:25787952

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.

Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

PubMed

Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

2016-10-01

Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of immune factors regulating antitumor immunity using polymeric vaccines with multiple adjuvants.

PubMed

Ali, Omar A; Verbeke, Catia; Johnson, Chris; Sands, R Warren; Lewin, Sarah A; White, Des; Doherty, Edward; Dranoff, Glenn; Mooney, David J

2014-03-15

The innate cellular and molecular components required to mediate effective vaccination against weak tumor-associated antigens remain unclear. In this study, we used polymeric cancer vaccines incorporating different classes of adjuvants to induce tumor protection, to identify dendritic cell (DC) subsets and cytokines critical to this efficacy. Three-dimensional, porous polymer matrices loaded with tumor lysates and presenting distinct combinations of granulocyte macrophage colony-stimulating factor (GM-CSF) and various Toll-like receptor (TLR) agonists affected 70% to 90% prophylactic tumor protection in B16-F10 melanoma models. In aggressive, therapeutic B16 models, the vaccine systems incorporating GM-CSF in combination with P(I:C) or CpG-ODN induced the complete regression of solid tumors (≤40 mm(2)), resulting in 33% long-term survival. Regression analysis revealed that the numbers of vaccine-resident CD8(+) DCs, plasmacytoid DCs (pDC), along with local interleukin (IL)-12, and granulocyte colony-stimulating factor (G-CSF) concentrations correlated strongly to vaccine efficacy regardless of adjuvant type. Furthermore, vaccine studies in Batf3(-/-) mice revealed that CD8(+) DCs are required to affect tumor protection, as vaccines in these mice were deficient in cytotoxic T lymphocytes priming and IL-12 induction in comparison with wild-type. These studies broadly demonstrate that three-dimensional polymeric vaccines provide a potent platform for prophylactic and therapeutic protection, and can be used as a tool to identify critical components of a desired immune response. Specifically, these results suggest that CD8(+) DCs, pDCs, IL-12, and G-CSF play important roles in priming effective antitumor responses with these vaccines. ©2014 AACR.

Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system.

PubMed

Cheng, Liang; Zhang, Zheng; Li, Guangming; Li, Feng; Wang, Li; Zhang, Liguo; Zurawski, Sandra M; Zurawski, Gerard; Levy, Yves; Su, Lishan

2017-10-27

TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro. For example, CpG-A was most efficient to induce IFN-α production in vitro. In contrast, CpG-B, R848 and Poly I:C stimulated much more IFN-α than CpG-A in vivo. Importantly, the human innate immune response to specific TLR-Ls in humanized mice was different from that reported in C57BL/6 mice, but similar to that reported in nonhuman primates. Furthermore, we found that different TLR-Ls distinctively activated and mobilized human plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs) and monocytes in different organs. Finally, we showed that, as adjuvants, CpG-B, R848 and Poly I:C can all enhance antigen specific CD4 + T cell response, while only R848 and Poly I:C induced CD8 + cytotoxic T cells response to a CD40-targeting HIV vaccine in humanized mice, correlated with their ability to activate human mDCs but not pDCs. We conclude that humanized mice serve as a highly relevant model to evaluate and rank the human immunologic effects of novel adjuvants in vivo prior to testing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spectroscopic and Mechanical Properties of a New Generation of Bulk Fill Composites

PubMed Central

Monterubbianesi, Riccardo; Orsini, Giovanna; Tosi, Giorgio; Conti, Carla; Librando, Vito; Procaccini, Maurizio; Putignano, Angelo

2016-01-01

Objectives: The aims of this study were to in vitro evaluate the degree of conversion and the microhardness properties of five bulk fill resin composites; in addition, the performance of two curing lamps, used for composites polymerization, was also analyzed. Materials and Methods: The following five resin-based bulk fill composites were tested: SureFil SDR®, Fill Up!™, Filtek™, SonicFill™, and SonicFill2™. Samples of 4 mm in thickness were prepared using Teflon molds filled in one increment and light-polymerized using two LED power units. Ten samples for each composite were cured using Elipar S10 and 10 using Demi Ultra. Additional samples of SonicFill2, (3 and 5 mm-thick) were also tested. The degree of conversion (DC) was determined by Raman spectroscopy, while the Vickers microhardness (VMH) was evaluated using a microhardness tester. The experimental evaluation was carried out on top and bottom sides, immediately after curing (t0), and, on bottom, after 24 h (t24). Two-ways analysis of variance was applied to evaluate DC and VMH-values. In all analyses, the level of significance was set at p < 0.05. Results: All bulk fill resin composites recorded satisfactory DCs on top and bottom sides. At t0, the top of SDR and SonicFill2 showed the highest DCs-values (85.56 ± 9.52 and 85.47 ± 1.90, respectively), when cured using Elipar S10; using Demi Ultra, SonicFill2 showed the highest DCs-values (90.53 ± 2.18). At t0, the highest DCs-values of bottom sides were recorded by SDR (84.64 ± 11.68), when cured using Elipar S10, and Filtek (81.52 ± 4.14), using Demi Ultra. On top sides, Demi Ultra lamp showed significant higher DCs compared to the Elipar S10 (p < 0.05). SonicFill2 reached suitable DCs also on bottom of 5 mm-thick samples. At t0, VMH-values ranged between 24.4 and 69.18 for Elipar S10, and between 26.5 and 67.3 for Demi Ultra. Using both lamps, the lowest VMH-values were shown by SDR, while the highest values by SonicFill2. At t24, all DC and VMH values significantly increased. Conclusions: Differences in DC and VMH among materials are suggested to be material and curing lamp dependent. Even at t0, the three high viscosity bulk composites showed higher VMH than the flowable or dual curing composites. PMID:28082918

Spectroscopic and Mechanical Properties of a New Generation of Bulk Fill Composites.

PubMed

Monterubbianesi, Riccardo; Orsini, Giovanna; Tosi, Giorgio; Conti, Carla; Librando, Vito; Procaccini, Maurizio; Putignano, Angelo

2016-01-01

Objectives: The aims of this study were to in vitro evaluate the degree of conversion and the microhardness properties of five bulk fill resin composites; in addition, the performance of two curing lamps, used for composites polymerization, was also analyzed. Materials and Methods: The following five resin-based bulk fill composites were tested: SureFil SDR®, Fill Up!™, Filtek™, SonicFill™, and SonicFill2™. Samples of 4 mm in thickness were prepared using Teflon molds filled in one increment and light-polymerized using two LED power units. Ten samples for each composite were cured using Elipar S10 and 10 using Demi Ultra. Additional samples of SonicFill2, (3 and 5 mm-thick) were also tested. The degree of conversion (DC) was determined by Raman spectroscopy, while the Vickers microhardness (VMH) was evaluated using a microhardness tester. The experimental evaluation was carried out on top and bottom sides, immediately after curing (t0), and, on bottom, after 24 h (t24). Two-ways analysis of variance was applied to evaluate DC and VMH-values. In all analyses, the level of significance was set at p < 0.05. Results: All bulk fill resin composites recorded satisfactory DCs on top and bottom sides. At t0, the top of SDR and SonicFill2 showed the highest DCs-values (85.56 ± 9.52 and 85.47 ± 1.90, respectively), when cured using Elipar S10; using Demi Ultra, SonicFill2 showed the highest DCs-values (90.53 ± 2.18). At t0, the highest DCs-values of bottom sides were recorded by SDR (84.64 ± 11.68), when cured using Elipar S10, and Filtek (81.52 ± 4.14), using Demi Ultra. On top sides, Demi Ultra lamp showed significant higher DCs compared to the Elipar S10 ( p < 0.05). SonicFill2 reached suitable DCs also on bottom of 5 mm-thick samples. At t0, VMH-values ranged between 24.4 and 69.18 for Elipar S10, and between 26.5 and 67.3 for Demi Ultra. Using both lamps, the lowest VMH-values were shown by SDR, while the highest values by SonicFill2. At t24, all DC and VMH values significantly increased. Conclusions: Differences in DC and VMH among materials are suggested to be material and curing lamp dependent. Even at t0, the three high viscosity bulk composites showed higher VMH than the flowable or dual curing composites.

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.

λ-Carrageenan improves the antitumor effect of dendritic cellbased vaccine.

PubMed

Li, Jinyao; Aipire, Adila; Li, Jinyu; Zhu, Hongge; Wang, Yanping; Guo, Wenjia; Li, Xiaoqin; Yang, Jia; Liu, Chunling

2017-05-02

In this study, we investigated the effect of λ-carrageenan on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. The frequencies of CD4+ and CD8+ T cells in spleens of tumor mice and their activation status were significantly increased in HPV-CGN-DC group, but the frequencies of natural regulatory T cells and CD11b+Gr-1+ cells were significantly decreased. Further, HPV-CGN-DC induced strong CD8+ T cell responses, which are negatively correlated with tumor volumes. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.

Adaptor protein-3 is required in dendritic cells for optimal Toll-like receptor signaling from phagosomes and antigen presentation to CD4+ T cells

PubMed Central

Mantegazza, Adriana R.; Guttentag, Susan H.; El-Benna, Jamel; Sasai, Miwa; Iwasaki, Akiko; Shen, Hao; Laufer, Terri M.; Marks, Michael S.

2012-01-01

SUMMARY Effective major histocompatibility complex-II (MHC-II) antigen presentation from phagocytosed particles requires phagosome-intrinsic toll-like receptor (TLR) signaling, but the molecular mechanisms underlying TLR delivery to phagosomes and how signaling regulates antigen presentation are incompletely understood. We show a requirement in dendritic cells (DCs) for adaptor protein-3 (AP-3) in efficient TLR recruitment to phagosomes and MHC-II presentation of antigens internalized by phagocytosis but not receptor-mediated endocytosis. DCs from AP-3-deficient pearl mice elicited impaired CD4+ T cell activation and Th1 effector function to particulate antigen in vitro and to recombinant Listeria monocytogenes infection in vivo. Whereas phagolysosome maturation and peptide:MHC-II complex assembly proceeded normally in pearl DCs, peptide:MHC-II export to the cell surface was impeded. This correlated with reduced TLR4 recruitment and proinflammatory signaling from phagosomes by particulate TLR ligands. We propose that AP-3-dependent TLR delivery from endosomes to phagosomes and subsequent signaling mobilize peptide:MHC-II export from intracellular stores. PMID:22560444

Antigen-specific IL-23/17 pathway activation by murine semi-mature DC-like cells

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

Nagasaka, Shinya; Iwasaki, Takumi; Okano, Tomoko

We analyzed the phenotype and function of bone marrow-derived dendritic cells (DCs) induced in vitro without using any serum during the late stage of cultivation. These 'serum-free' DCs (SF-DCs) possessed the ability to induce T cell proliferation as well as antibody responses, indicating that they were functional DCs. Surprisingly, the SF-DCs akin to semi-mature DCs in terms of both phenotypic and functional characteristics. The SF-DCs did not produce IL-12 but produced large amounts of IL-23 following lipopolysaccharide stimulation. The antigen-specific production of IL-17 by CD4{sup +} T cells co-cultured with OVA-loaded SF-DCs was significantly higher than that with OVA-loaded conventionalmore » DCs. These results suggest that SF-DCs tend to produce IL-23 and can consequently induce the IL-17 producing CD4{sup +} T cells. The semi-mature DC-like cells reported here will be useful vehicles for DC immunization and might contribute to studies on the possible involvement of semi-mature DCs in Th17 cell differentiation.« less

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.

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes and progenitors

PubMed Central

Villani, Alexandra-Chloé; Satija, Rahul; Reynolds, Gary; Sarkizova, Siranush; Shekhar, Karthik; Fletcher, James; Griesbeck, Morgane; Butler, Andrew; Zheng, Shiwei; Lazo, Suzan; Jardine, Laura; Dixon, David; Stephenson, Emily; Nilsson, Emil; Grundberg, Ida; McDonald, David; Filby, Andrew; Li, Weibo; De Jager, Philip L.; Rozenblatt-Rosen, Orit; Lane, Andrew A.; Haniffa, Muzlifah; Regev, Aviv; Hacohen, Nir

2017-01-01

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals: a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease. PMID:28428369

Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor.

PubMed

Sathe, Priyanka; Metcalf, Donald; Vremec, David; Naik, Shalin H; Langdon, Wallace Y; Huntington, Nicholas D; Wu, Li; Shortman, Ken

2014-07-17

The relationship between dendritic cells (DCs) and macrophages is often debated. Here we ask whether steady-state, lymphoid-tissue-resident conventional DCs (cDCs), plasmacytoid DCs (pDCs), and macrophages share a common macrophage-DC-restricted precursor (MDP). Using new clonal culture assays combined with adoptive transfer, we found that MDP fractions isolated by previous strategies are dominated by precursors of macrophages and monocytes, include some multipotent precursors of other hematopoietic lineages, but contain few precursors of resident cDCs and pDCs and no detectable common precursors restricted to these DC types and macrophages. Overall we find no evidence for a common restricted MDP leading to both macrophages and FL-dependent, resident cDCs and pDCs. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

A Tec kinase BTK inhibitor ibrutinib promotes maturation and activation of dendritic cells.

PubMed

Natarajan, Gayathri; Oghumu, Steve; Terrazas, Cesar; Varikuti, Sanjay; Byrd, John C; Satoskar, Abhay R

2016-06-01

Ibrutinib, a BTK inhibitor, is currently used to treat various hematological malignancies. We evaluated whether ibrutinib treatment during development of murine bone marrow-derived dendritic cells (DCs) modulates their maturation and activation. Ibrutinib treatment increased the proportion of CD11c(+) DCs, upregulated the expression of MHC-II and CD80 and downregulated Ly6C expression by DCs. Additionally, ibrutinib treatment led to an increase in MHC-II(+), CD80(+) and CCR7(+) DCs but a decrease in CD86(+) DCs upon LPS stimulation. LPS/ibrutinib-treated DCs displayed increased IFNβ and IL-10 synthesis and decreased IL-6, IL-12 and NO production compared to DCs stimulated with LPS alone. Finally, LPS/ibrutinib-treated DCs promoted higher rates of CD4(+) T cell proliferation and cytokine production compared to LPS only stimulated DCs. Taken together, our results indicate that ibrutinib enhances the maturation and activation of DCs to promote CD4(+) T cell activation which could be exploited for the development of DC-based cancer therapies.

Induction of anti-HBs in HB vaccine nonresponders in vivo by hepatitis B surface antigen-pulsed blood dendritic cells.

PubMed

Fazle Akbar, Sk Md; Furukawa, Shinya; Yoshida, Osamu; Hiasa, Yoichi; Horiike, Norio; Onji, Morikazu

2007-07-01

Antigen-pulsed dendritic cells (DCs) are now used for treatment of patients with cancers, however, the efficacy of these DCs has never been evaluated for prophylactic purposes. The aim of this study was (1) to prepare hepatitis B surface antigen (HBsAg)-pulsed human blood DCs, (2) to assess immunogenicity of HBsAg-pulsed DCs in vitro and (3) to evaluate the efficacy of HBsAg-pulsed DCs in hepatitis B (HB) vaccine nonresponders. Human peripheral blood DCs were cultured with HBsAg to prepare HBsAg-pulsed DCs. The expression of immunogenic epitopes of HBsAg on HBsAg-pulsed DCs was assessed in vitro. Finally, HBsAg-pulsed DCs were administered, intradermally to six HB vaccine nonresponders and the levels of antibody to HBsAg (anti-HBs) in the sera were assessed. HB vaccine nonresponders did not exhibit features of immediate, early or delayed adverse reactions due to administration of HBsAg-pulsed DCs. Anti-HBs were detected in the sera of all HB vaccine nonresponders within 28 days after administration of HBsAg-pulsed DCs. This study opens a new field of application of antigen-pulsed DCs for prophylactic purposes when adequate levels of protective antibody cannot be induced by traditional vaccination approaches.

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

The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors.

PubMed

Seidel, Kathleen; Beck, Jürgen; Stieglitz, Lennart; Schucht, Philippe; Raabe, Andreas

2013-02-01

Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST. A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration 500 μsec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively. The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11-20 mA, n = 13; 6-10 mA, n = 20; 4-5 mA, n = 30; and 1-3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1-3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits. Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

Biomarkers for Allergen Immunotherapy: A "Panoromic" View.

PubMed

Moingeon, Philippe

2016-02-01

Biomarkers (BMKs) are biological parameters that can be measured to predict or monitor disease severity or treatment efficacy. The induction of regulatory dendritic cells (DCs) concomitantly with a downregulation of proallergic DC2s (ie, DCs supporting the differentiation of T-helper lymphocyte type 2 cells) in the blood of patients allergic to grass pollen has been correlated with the early onset of allergen immunotherapy efficacy. The combined use of omics technologies to compare biological samples from clinical responders and nonresponders is being implemented in the context of nonhypothesis-driven approaches. Such comprehensive "panoromic" strategies help identify completely novel candidate BMKs, to be subsequently validated as companion diagnostics in large-scale clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Amelioration of collagen-induced arthritis using antigen-loaded dendritic cells modified with NF-κB decoy oligodeoxynucleotides

PubMed Central

Jiang, Hongmei; Hu, Henggui; Zhang, Yali; Yue, Ping; Ning, Lichang; Zhou, Yan; Shi, Ping; Yuan, Rui

2017-01-01

Dendritic cells (DCs) play an important role in the initiation of autoimmunity in rheumatoid arthritis (RA); therefore, the use of DCs needs to be explored to develop new therapeutic approaches for RA. Here, we investigated the therapeutic effect of bovine type II collagen (BIIC)-loaded DCs modified with NF-κB decoy oligodeoxynucleotides (ODNs) on collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms. DCs treated with BIIC and NF-κB decoy ODNs exhibited features of immature DCs with low levels of costimulatory molecule (CD80 and CD86) expression. The development of arthritis in rats with CIA injected with BIIC + NF-κB decoy ODN-propagated DCs (BIIC–decoy DCs) was significantly ameliorated compared to that in rats injected with BIIC-propagated DCs or phosphate-buffered saline. We also found that the BIIC–decoy DCs exerted antiarthritis effects by inhibiting self-lymphocyte proliferative response and suppressing IFN-γ and anti-BIIC antibody production and inducing IL-10 antibody production. Additionally, antihuman serum antibodies were successfully produced in the rats treated with BIIC–decoy DCs but not in those treated with NF-κB decoy ODN-propagated DCs; moreover, the BIIC–decoy DCs did not affect immune function in the normal rats. These findings suggested that NF-κB decoy ODN-modified DCs loaded with a specific antigen might offer a practical method for the treatment of human RA. PMID:29075103

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

The effects of elevated pain inhibition on endurance exercise performance.

PubMed

Flood, Andrew; Waddington, Gordon; Keegan, Richard J; Thompson, Kevin G; Cathcart, Stuart

2017-01-01

The ergogenic effects of analgesic substances suggest that pain perception is an important regulator of work-rate during fatiguing exercise. Recent research has shown that endogenous inhibitory responses, which act to attenuate nociceptive input and reduce perceived pain, can be increased following transcranial direct current stimulation of the hand motor cortex. Using high-definition transcranial direct current stimulation (HD-tDCS; 2 mA, 20 min), the current study aimed to examine the effects of elevated pain inhibitory capacity on endurance exercise performance. It was hypothesised that HD-tDCS would enhance the efficiency of the endogenous pain inhibitory response and improve endurance exercise performance. Twelve healthy males between 18 and 40 years of age ( M  = 24.42 ± 3.85) were recruited for participation. Endogenous pain inhibitory capacity and exercise performance were assessed before and after both active and sham (placebo) stimulation. The conditioned pain modulation protocol was used for the measurement of pain inhibition. Exercise performance assessment consisted of both maximal voluntary contraction (MVC) and submaximal muscular endurance performance trials using isometric contractions of the non-dominant leg extensors. Active HD-tDCS (pre-tDCS, -.32 ± 1.33 kg; post-tDCS, -1.23 ± 1.21 kg) significantly increased pain inhibitory responses relative to the effects of sham HD-tDCS (pre-tDCS, -.91 ± .92 kg; post-tDCS, -.26 ± .92 kg; p  = .046). Irrespective of condition, peak MVC force and muscular endurance was reduced from pre- to post-stimulation. HD-tDCS did not significantly influence this reduction in maximal force (active: pre-tDCS, 264.89 ± 66.87 Nm; post-tDCS, 236.33 ± 66.51 Nm; sham: pre-tDCS, 249.25 ± 88.56 Nm; post-tDCS, 239.63 ± 67.53 Nm) or muscular endurance (active: pre-tDCS, 104.65 ± 42.36 s; post-tDCS, 93.07 ± 33.73 s; sham: pre-tDCS, 123.42 ± 72.48 s; post-tDCS, 100.27 ± 44.25 s). Despite increasing pain inhibitory capacity relative to sham stimulation, active HD-tDCS did not significantly elevate maximal force production or muscular endurance. These findings question the role of endogenous pain inhibitory networks in the regulation of exercise performance.

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.

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

PubMed Central

2012-01-01

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

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

PubMed

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

2012-11-30

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

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.

Interprofessional collaboration and job satisfaction of chiropractic physicians.

PubMed

Konrad, Thomas R; Fletcher, Grant S; Carey, Timothy S

2004-05-01

Despite the fact that chiropractic physicians (DCs) are growing in number and legitimacy in the community of health care professionals, little recent research describes how their relationships with medical doctors (MDs) affect their job and career perceptions. This study explores interprofessional relations by identifying factors associated with variations in how DCs evaluate their interaction with MDs. It also adapts a previously validated multifaceted measure of MD job satisfaction for use with DCs. Cross-sectional survey of 311 DC physicians in North Carolina. The hypothesized multifaceted nature of DC job satisfaction was confirmed. Four distinct job facets and global career satisfaction were measured effectively in DCs. DCs' career satisfaction is related to satisfaction with compensation, intrinsic motivation of relating to patients, and having positive relationships with DC colleagues. DCs report referring patients to MDs more often than they report MDs referring patients to them. Satisfaction with relationships between DCs and MDs is relatively low and is strongly linked to the quantity of referrals from MDs and the perception that MDs practice collaboratively with DCs. However, DCs' global career satisfaction is unrelated to their relationships with MDs. Global career satisfaction of DCs is relatively high and unaffected by the low level of satisfaction DCs report having with their relationships with MDs. These findings suggest that despite increasing interaction and interdependence, DCs' relationship with MDs is of minor importance in their professional self-image.

Use of tDCS in Aphasia Rehabilitation: A Systematic Review of the Behavioral Interventions Implemented With Noninvasive Brain Stimulation for Language Recovery.

PubMed

Galletta, Elizabeth E; Conner, Peggy; Vogel-Eyny, Amy; Marangolo, Paola

2016-12-01

The purpose of this article is to review the behavioral treatments used in aphasia rehabilitation research that have been combined with transcranial direct current stimulation (tDCS). Although tDCS in aphasia treatment has shown promise, the results have not been conclusive, and their interpretation is further compounded by the heterogeneity of study characteristics. Because implementing a behavioral task during brain stimulation has been shown to be pivotal to the adjuvant effects of tDCS, we analyze the behavioral treatments that have been paired with tDCS. A computerized database search (PubMed) was completed to document and review aphasia treatment studies that combine behavioral treatment with noninvasive brain stimulation in the form of tDCS. Two authors reviewed each aphasia tDCS article published between 2008 and 2015 and evaluated (a) the behavioral interventions for aphasia that have been combined with tDCS, and (b) the methodological variables that may have influenced language outcomes in the tDCS aphasia literature. A review of the behavioral treatments implemented in tDCS aphasia rehabilitation studies highlights several methodological considerations for future investigations. Impairment-focused and pragmatic treatments have been implemented in tDCS aphasia research studies. No one behavioral approach stands out as the best treatment to combine with tDCS for the promotion of language recovery.

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

miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1

PubMed Central

Su, Xiaoping; Qian, Cheng; Zhang, Qian; Hou, Jin; Gu, Yan; Han, Yanmei; Chen, Yongjian; Jiang, Minghong; Cao, Xuetao

2013-01-01

Dendritic cells (DCs) are critical to initiate the immune response and maintain tolerance, depending on different status and subsets. The expression profiles of microRNAs (miRNAs) in various DC subsets and haematopoietic stem cells (HSCs), which generate DCs, remain to be fully identified. Here we examine miRNomes of mouse bone marrow HSCs, immature DCs, mature DCs and IL-10/NO-producing regulatory DCs by deep sequencing. We identify numerous stage-specific miRNAs and histone modification in HSCs and DCs at different differentiation stages. miR-30b, significantly upregulated via a TGF-beta/Smad3-mediated epigenetic pathway in regulatory DCs, can target Notch1 to promote IL-10 and NO production, suggesting that miR-30b is a negative regulator of immune response. We also identify miRNomes of in vivo counterparts of mature DCs and regulatory DCs and systematically compare them with DCs cultured in vitro. These results provide a resource for studying roles of miRNAs in stem cell biology, development and functional regulation of DC subsets. PMID:24309499

A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery

PubMed Central

Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

2016-01-01

The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients. PMID:26959879

A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery.

PubMed

Wang, Di; Yang, Xin-lu; Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

2016-04-05

The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients.

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

Variation and significance of secretory immunoglobulin A, interleukin 6 and dendritic cells in oral cancer.

PubMed

Zhang, Suxin; Zhang, Xin; Yin, Ke; Li, Tianke; Bao, Yang; Chen, Zhong

2017-04-01

The present study aimed to determine changes in the concentration of secretory immunoglobulin A (SIgA) and interleukin 6 (IL-6) in the saliva of patients with oral cancer, to evaluate the abnormal expression of cluster of differentiation (CD) 1a, CD83, CD80 and CD86 on dendritic cells (DCs) of oral cancer tissues and to discuss the interaction between SIgA, IL-6 and DCs in oral cancer. A total of 40 patients between 27 and 70 years of age, median age 52 years, with primary oral cancer were enrolled in the present study, and a group of 20 healthy male and female volunteers was used as the control group. The concentration of SIgA and IL-6 in the saliva of the preoperative patients was determined by ELISA. The expression levels of CD1a, CD83, CD80 and CD86 were detected by immunohistochemistry and flow cytometry, which was performed on histopathological sections from paraffin-embedded tumor and corresponding adjacent control tissues. The specimens were assessed using the semi-quantitative immunoreactive score (IRS). The concentration of SIgA in the saliva from patients with oral cancer decreased, whereas the IL-6 level significantly increased compared with the control subjects (P<0.05). In addition, the decrease of SIgA level and increase of IL-6 level exhibited a negative correlation (r=-0.543, P<0.05). According to the IRS score, the expression levels of CD1a, CD83, CD80 and CD86 in the cancer tissue were lower than the expression levels of the control group (P<0.05). Furthermore, the expression of CD80 and CD86 exhibited no correlation with histological grade or pathological type (P>0.05), but exhibited a negative correlation with clinical stage and lymph node metastasis (P<0.05). The concentration of SIgA and IL-6 in saliva may be used as an auxiliary diagnostic indicator for oral cancer. The detection of CD80 and CD86 expressed on DCs in oral cancer tissue may be useful for the diagnosis and evaluation of the prognosis of tumors. The present study hypothesized that the use of SIgA vaccines or IL-6 inhibitors may be useful for reversing the immune deficiency associated with DCs in oral cancer.

A short protocol using dexamethasone and monophosphoryl lipid A generates tolerogenic dendritic cells that display a potent migratory capacity to lymphoid chemokines

PubMed Central

2013-01-01

Background Generation of tolerogenic dendritic cells (TolDCs) for therapy is challenging due to its implications for the design of protocols suitable for clinical applications, which means not only using safe products, but also working at defining specific biomarkers for TolDCs identification, developing shorter DCs differentiation methods and obtaining TolDCs with a stable phenotype. We describe here, a short-term protocol for TolDCs generation, which are characterized in terms of phenotypic markers, cytokines secretion profile, CD4+ T cell-stimulatory ability and migratory capacity. Methods TolDCs from healthy donors were generated by modulation with dexamethasone plus monophosphoryl lipid A (MPLA-tDCs). We performed an analysis of MPLA-tDCs in terms of yield, viability, morphology, phenotypic markers, cytokines secretion profile, stability, allogeneic and antigen-specific CD4+ T-cell stimulatory ability and migration capacity. Results After a 5-day culture, MPLA-tDCs displayed reduced expression of costimulatory and maturation molecules together to an anti-inflammatory cytokines secretion profile, being able to maintain these tolerogenic features even after the engagement of CD40 by its cognate ligand. In addition, MPLA-tDCs exhibited reduced capabilities to stimulate allogeneic and antigen-specific CD4+ T cell proliferation, and induced an anti-inflammatory cytokine secretion pattern. Among potential tolerogenic markers studied, only TLR-2 was highly expressed in MPLA-tDCs when compared to mature and immature DCs. Remarkable, like mature DCs, MPLA-tDCs displayed a high CCR7 and CXCR4 expression, both chemokine receptors involved in migration to secondary lymphoid organs, and even more, in an in vitro assay they exhibited a high migration response towards CCL19 and CXCL12. Conclusion We describe a short-term protocol for TolDC generation, which confers them a stable phenotype and migratory capacity to lymphoid chemokines, essential features for TolDCs to be used as therapeutics for autoimmunity and prevention of graft rejection. PMID:23706017

Ambulation Increases Decompression Sickness in Altitude Exposure

NASA Technical Reports Server (NTRS)

Conkin, Johnny; Pollock, N. W.; Natoli, M. J.; Wessel, J. H., III; Gernhardt, M. L.

2014-01-01

INTRODUCTION - Exercise accelerates inert gas elimination during oxygen breathing prior to decompression (prebreathe), but may also promote bubble formation and increase the risk of decompression sickness (DCS). The timing, pattern and intensity of exercise are likely critical to the net effect. The NASA Prebreathe Reduction Program (PRP) combined oxygen prebreathe and exercise preceding a 4.3 psi exposure in non-ambulatory subjects (a microgravity analog) to produce two protocols now used by astronauts preparing for extravehicular activity (CEVIS and ISLE). Additional work is required to investigate whether exercise normal to 1 G environments increases the risk of DCS over microgravity simulation. METHODS - The CEVIS protocol was replicated with one exception. Our subjects completed controlled ambulation (walking in place with fixed cadence and step height) during both preflight and at 4.3 psi instead of remaining non-ambulatory throughout. Decompression stress was graded with aural Doppler (Spencer 0-IV scale). Two-dimensional echocardiographic imaging was used to look for left heart gas emboli (the presence of which prompted test termination). Venous blood was collected at three points to correlate Doppler measures of decompression stress with microparticle (cell fragment) accumulation. Fisher Exact Tests compared test and control groups. Trial suspension would occur when DCS risk >15% or grade IV venous gas emboli (VGE) risk >20% (at 70% confidence). RESULTS - Eleven person-trials were completed (9 male, 2 female) when DCS prompted suspension. DCS was greater than in CEVIS trials (3/11 [27%] vs. 0/45 [0%], respectively, p=0.03). Statistical significance was not reached for peak grade IV VGE (2/11 [18%] vs. 3/45 [7%], p=0.149) or cumulative grade IV VGE observations per subject-trial (8/128 [6%] vs. 26/630 [4%], p=0.151). Microparticle data were collected for 5/11 trials (3 with DCS outcomes), with widely varying patterns that could not be resolved statistically. CONCLUSION - We did find that that ambulation increases decompression stress. Additional trials would improve the statistical power to assess differences in VGE and to evaluate the relationship between decompression stress and microparticles.

Tim-3 is a Marker of Plasmacytoid Dendritic Cell Dysfunction during HIV Infection and Is Associated with the Recruitment of IRF7 and p85 into Lysosomes and with the Submembrane Displacement of TLR9.

PubMed

Schwartz, Jordan Ari; Clayton, Kiera L; Mujib, Shariq; Zhang, Hongliang; Rahman, A K M Nur-Ur; Liu, Jun; Yue, Feng Yun; Benko, Erika; Kovacs, Colin; Ostrowski, Mario A

2017-04-15

In chronic diseases, such as HIV infection, plasmacytoid dendritic cells (pDCs) are rendered dysfunctional, as measured by their decreased capacity to produce IFN-α. In this study, we identified elevated levels of T cell Ig and mucin-domain containing molecule-3 (Tim-3)-expressing pDCs in the blood of HIV-infected donors. The frequency of Tim-3-expressing pDCs correlated inversely with CD4 T cell counts and positively with HIV viral loads. A lower frequency of pDCs expressing Tim-3 produced IFN-α or TNF-α in response to the TLR7 agonists imiquimod and Sendai virus and to the TLR9 agonist CpG. Thus, Tim-3 may serve as a biomarker of pDC dysfunction in HIV infection. The source and function of Tim-3 was investigated on enriched pDC populations from donors not infected with HIV. Tim-3 induction was achieved in response to viral and artificial stimuli, as well as exogenous IFN-α, and was PI3K dependent. Potent pDC-activating stimuli, such as CpG, imiquimod, and Sendai virus, induced the most Tim-3 expression and subsequent dysfunction. Small interfering RNA knockdown of Tim-3 increased IFN-α secretion in response to activation. Intracellular Tim-3, as measured by confocal microscopy, was dispersed throughout the cytoplasm prior to activation. Postactivation, Tim-3 accumulated at the plasma membrane and associated with disrupted TLR9 at the submembrane. Tim-3-expressing pDCs had reduced IRF7 levels. Furthermore, intracellular Tim-3 colocalized with p85 and IRF7 within LAMP1 + lysosomes, suggestive of a role in degradation. We conclude that Tim-3 is a biomarker of dysfunctional pDCs and may negatively regulate IFN-α, possibly through interference with TLR signaling and recruitment of IRF7 and p85 into lysosomes, enhancing their degradation. Copyright © 2017 by The American Association of Immunologists, Inc.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

PubMed

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury

PubMed Central

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H.

2016-01-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 minutes after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 minutes. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS + c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 minutes/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 minutes of daily stimulation compared with 6 hours, as in our prior study, making it a potential therapy for humans with spinal cord injury. PMID:26708732

Avian dark cells

NASA Technical Reports Server (NTRS)

Hara, J.; Plymale, D. R.; Shepard, D. L.; Hara, H.; Garry, Robert F.; Yoshihara, T.; Zenner, Hans-Peter; Bolton, M.; Kalkeri, R.; Fermin, Cesar D.

2002-01-01

Dark cells (DCs) of mammalian and non-mammalian species help to maintain the homeostasis of the inner ear fluids in vivo. Although the avian cochlea is straight and the mammalian cochlea is coiled, no significant difference in the morphology and/or function of mammalian and avian DCs has been reported. The mammalian equivalent of avian DCs are marginal cells and are located in the stria vascularis along a bony sheet. Avian DCs hang free from the tegmentum vasculosum (TV) of the avian lagena between the perilymph and endolymph. Frame averaging was used to image the fluorescence emitted by several fluorochromes applied to freshly isolated dark cells (iDCs) from chickens (Gallus domesticus) inner ears. The viability of iDCs was monitored via trypan blue exclusion at each isolation step. Sodium Green, BCECF-AM, Rhodamine 123 and 9-anthroyl ouabain molecules were used to test iDC function. These fluorochromes label iDCs ionic transmembrane trafficking function, membrane electrogenic potentials and Na+/K+ ATPase pump's activity. Na+/K+ ATPase pump sites, were also evaluated by the p-nitrophenyl phosphatase reaction. These results suggest that iDCs remain viable for several hours after isolation without special culturing requirements and that the number and functional activity of Na+/K+ ATPase pumps in the iDCs were indistinguishable from in vivo DCs. Primary cultures of freshly iDCs were successfully maintained for 28 days in plastic dishes with RPMI 1640 culture medium. The preparation of iDCs overcomes the difficulty of DCs accessability in vivo and the unavoidable contamination that rupturing the inner ear microenvironments induces.

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

Residual Endotoxin Contaminations in Recombinant Proteins Are Sufficient to Activate Human CD1c+ Dendritic Cells

PubMed Central

Schwarz, Harald; Schmittner, Maria; Duschl, Albert; Horejs-Hoeck, Jutta

2014-01-01

Many commercially available recombinant proteins are produced in Escherichia coli, and most suppliers guarantee contamination levels of less than 1 endotoxin unit (EU). When we analysed commercially available proteins for their endotoxin content, we found contamination levels in the same range as generally stated in the data sheets, but also some that were higher. To analyse whether these low levels of contamination have an effect on immune cells, we stimulated the monocytic cell line THP-1, primary human monocytes, in vitro differentiated human monocyte-derived dendritic cells, and primary human CD1c+ dendritic cells (DCs) with very low concentrations of lipopolysaccharide (LPS; ranging from 0.002–2 ng/ml). We show that CD1c+ DCs especially can be activated by minimal amounts of LPS, equivalent to the levels of endotoxin contamination we detected in some commercially available proteins. Notably, the enhanced endotoxin sensitivity of CD1c+ DCs was closely correlated with high CD14 expression levels observed in CD1c+ DCs that had been maintained in cell culture medium for 24 hours. When working with cells that are particularly sensitive to LPS, even low endotoxin contamination may generate erroneous data. We therefore recommend that recombinant proteins be thoroughly screened for endotoxin contamination using the limulus amebocyte lysate test, fluorescence-based assays, or a luciferase based NF-κB reporter assay involving highly LPS-sensitive cells overexpressing TLR4, MD-2 and CD14. PMID:25478795

To what extent might N2 limit dive performance in king penguins?

PubMed

Fahlman, A; Schmidt, A; Jones, D R; Bostrom, B L; Handrich, Y

2007-10-01

A mathematical model was used to explore if elevated levels of N2, and risk of decompression sickness (DCS), could limit dive performance (duration and depth) in king penguins (Aptenodytes patagonicus). The model allowed prediction of blood and tissue (central circulation, muscle, brain and fat) N2 tensions (P(N2)) based on different cardiac outputs and blood flow distributions. Estimated mixed venous P(N2) agreed with values observed during forced dives in a compression chamber used to validate the assumptions of the model. During bouts of foraging dives, estimated mixed venous and tissue P(N2) increased as the bout progressed. Estimated mean maximum mixed venous P(N2) upon return to the surface after a dive was 4.56+/-0.18 atmospheres absolute (ATA; range: 4.37-4.78 ATA). This is equivalent to N2 levels causing a 50% DCS incidence in terrestrial animals of similar mass. Bout termination events were not associated with extreme mixed venous N2 levels. Fat P(N2) was positively correlated with bout duration and the highest estimated fat P(N2) occurred at the end of a dive bout. The model suggested that short and shallow dives occurring between dive bouts help to reduce supersaturation and thereby DCS risk. Furthermore, adipose tissue could also help reduce DCS risk during the first few dives in a bout by functioning as a sink to buffer extreme levels of N2.

Lymphopenia associated with highly virulent H5N1 virus infection due to plasmacytoid dendritic cell mediated apoptosis of T cells

PubMed Central

Boonnak, Kobporn; Vogel, Leatrice; Feldmann, Friederike; Feldmann, Heinz; Legge, Kevin L.; Subbarao, Kanta

2014-01-01

Although lymphopenia is a hallmark of severe infection with highly pathogenic H5N1 and the newly emerged H7N9 influenza viruses in humans, the mechanism(s) by which lethal H5N1 viruses cause lymphopenia in mammalian hosts remains poorly understood. Because influenza-specific T cell responses are initiated in the lung draining lymph nodes, and lymphocytes subsequently traffic to the lungs or peripheral circulation, we compared the immune responses in the lung draining lymph nodes following infection with a lethal A/HK/483/97 or non-lethal A/HK/486/97 (H5N1) virus in a mouse model. We found that lethal H5N1, but not non-lethal H5N1 virus infection in mice enhances Fas ligand (FasL) expression on plasmacytoid dendritic cells (pDCs), resulting in apoptosis of influenza-specific CD8+ T cells via a Fas-FasL mediated pathway. We also found that pDCs, but not other DC subsets, preferentially accumulate in the lung draining lymph nodes of lethal H5N1 virus-infected mice and that the induction of FasL expression on pDCs correlates with high levels of IL-12p40 monomer/homodimer in the lung draining lymph nodes. Our data suggest that one of the mechanisms of lymphopenia associated with lethal H5N1 virus infection involves a deleterious role for pDCs. PMID:24829418

Monitoring transcranial direct current stimulation induced changes in cortical excitability during the serial reaction time task.

PubMed

Ambrus, Géza Gergely; Chaieb, Leila; Stilling, Roman; Rothkegel, Holger; Antal, Andrea; Paulus, Walter

2016-03-11

The measurement of the motor evoked potential (MEP) amplitudes using single pulse transcranial magnetic stimulation (TMS) is a common method to observe changes in motor cortical excitability. The level of cortical excitability has been shown to change during motor learning. Conversely, motor learning can be improved by using anodal transcranial direct current stimulation (tDCS). In the present study, we aimed to monitor cortical excitability changes during an implicit motor learning paradigm, a version of the serial reaction time task (SRTT). Responses from the first dorsal interosseous (FDI) and forearm flexor (FLEX) muscles were recorded before, during and after the performance of the SRTT. Online measurements were combined with anodal, cathodal or sham tDCS for the duration of the SRTT. Negative correlations between the amplitude of online FDI MEPs and SRTT reaction times (RTs) were observed across the learning blocks in the cathodal condition (higher average MEP amplitudes associated with lower RTs) but no significant differences in the anodal and sham conditions. tDCS did not have an impact on SRTT performance, as would be predicted based on previous studies. The offline before-after SRTT MEP amplitudes showed an increase after anodal and a tendency to decrease after cathodal stimulation, but these changes were not significant. The combination of different interventions during tDCS might result in reduced efficacy of the stimulation that in future studies need further attention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2018-02-01

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

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.

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.

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

NASA Astrophysics Data System (ADS)

Jog, Mayank Anant

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

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

PubMed

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

2017-09-14

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

The Closely Related CD103+ Dendritic Cells (DCs) and Lymphoid-Resident CD8+ DCs Differ in Their Inflammatory Functions

PubMed Central

Jiao, Zhijun; Bedoui, Sammy; Brady, Jamie L.; Walter, Anne; Chopin, Michael; Carrington, Emma M.; Sutherland, Robyn M.; Nutt, Stephen L.; Zhang, Yuxia; Ko, Hyun-Ja; Wu, Li

2014-01-01

Migratory CD103+ and lymphoid-resident CD8+ dendritic cells (DCs) share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+ DCs. This superior capacity to drive Th17 responses was also evident in CD103+ DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103+ DCs compared with CD8+ DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103+ DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103+ DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs. PMID:24637385

Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis.

PubMed

Thomas, Katja; Dietze, Kristin; Wehner, Rebekka; Metz, Imke; Tumani, Hayrettin; Schultheiß, Thorsten; Günther, Claudia; Schäkel, Knut; Reichmann, Heinz; Brück, Wolfgang; Schmitz, Marc; Ziemssen, Tjalf

2014-10-01

To examine the potential role of 6-sulfo LacNAc(+) (slan) dendritic cells (DCs) displaying pronounced proinflammatory properties in the pathogenesis of multiple sclerosis (MS). We determined the presence of slanDCs in demyelinated brain lesions and CSF samples of patients with MS. In addition, we explored the impact of methylprednisolone, interferon-β, glatiramer acetate, or natalizumab on the frequency of blood-circulating slanDCs in patients with MS. We also evaluated whether interferon-β modulates important proinflammatory capabilities of slanDCs. SlanDCs accumulate in highly inflammatory brain lesions and are present in the majority of CSF samples of patients with MS. Short-term methylprednisolone administration reduces the percentage of slanDCs in blood of patients with MS and the proportion of tumor necrosis factor-α- or CD150-expressing slanDCs. Long-term interferon-β treatment decreases the percentage of blood-circulating slanDCs in contrast to glatiramer acetate or natalizumab. Furthermore, interferon-β inhibits the secretion of proinflammatory cytokines by slanDCs and their capacity to promote proliferation and differentiation of T cells. Accumulation of slanDCs in highly inflammatory brain lesions and their presence in CSF indicate that slanDCs may play an important role in the immunopathogenesis of MS. The reduction of blood-circulating slanDCs and the inhibition of their proinflammatory properties by methylprednisolone and interferon-β may contribute to the therapeutic efficiency of these drugs in patients with MS.

Accumulation and therapeutic modulation of 6-sulfo LacNAc+ dendritic cells in multiple sclerosis

PubMed Central

Thomas, Katja; Dietze, Kristin; Wehner, Rebekka; Metz, Imke; Tumani, Hayrettin; Schultheiß, Thorsten; Günther, Claudia; Schäkel, Knut; Reichmann, Heinz; Brück, Wolfgang; Schmitz, Marc

2014-01-01

Objective: To examine the potential role of 6-sulfo LacNAc+ (slan) dendritic cells (DCs) displaying pronounced proinflammatory properties in the pathogenesis of multiple sclerosis (MS). Methods: We determined the presence of slanDCs in demyelinated brain lesions and CSF samples of patients with MS. In addition, we explored the impact of methylprednisolone, interferon-β, glatiramer acetate, or natalizumab on the frequency of blood-circulating slanDCs in patients with MS. We also evaluated whether interferon-β modulates important proinflammatory capabilities of slanDCs. Results: SlanDCs accumulate in highly inflammatory brain lesions and are present in the majority of CSF samples of patients with MS. Short-term methylprednisolone administration reduces the percentage of slanDCs in blood of patients with MS and the proportion of tumor necrosis factor-α– or CD150-expressing slanDCs. Long-term interferon-β treatment decreases the percentage of blood-circulating slanDCs in contrast to glatiramer acetate or natalizumab. Furthermore, interferon-β inhibits the secretion of proinflammatory cytokines by slanDCs and their capacity to promote proliferation and differentiation of T cells. Conclusion: Accumulation of slanDCs in highly inflammatory brain lesions and their presence in CSF indicate that slanDCs may play an important role in the immunopathogenesis of MS. The reduction of blood-circulating slanDCs and the inhibition of their proinflammatory properties by methylprednisolone and interferon-β may contribute to the therapeutic efficiency of these drugs in patients with MS. PMID:25340085

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.

2014 Decompression Sickness/Extravehicular Activity Risks Standing Review Panel

NASA Technical Reports Server (NTRS)

Steinberg, Susan; Mahon, Richard; Klaus, David; Neuman, Tom; Pilmanis, Andrew; Regis, David

2014-01-01

The 2014 Decompression Sickness (DCS)/Extravehicular Activity (EVA) Risks Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on November 4 - 5, 2014. The SRP reviewed the Research Plans for The Risk of Decompression Sickness and the Risk of Injury and Compromised Performance due to EVA Operations, as well as the Evidence Reports for both of these Risks. The SRP found that the NASA DCS/EVA team did an excellent job of presenting their research plans. The SRP considers it critical that NASA proceeds with the high priority tasks identified in this report (DCS1, DCS3, DCS5). The highest priority is to determine the acceptable DCS and hypoxia risk associated with the planned human exploration beyond low Earth orbit. The risk of DCS is highly dependent upon the pressure within the exploration vehicle. If slightly more hypoxia is permitted then (even with the same percentage of oxygen) the pressure within the exploration vehicle can be lowered thus further mitigating the risk of DCS. The second highest priority is to test and validate the recommended 8.2psi/34% O2 atmosphere. Development of procedures and equipment for human exploration missions are very limited until the results of this testing are completed. The SRP also suggests that DCS7 be separated into two Gaps. Gap DCS7 should deal with DCS treatment while a new Gap should be created to deal with the long-term effects of DCS. The SRP also encourages NASA to increase collaboration with other organizations and pool resources where possible. The current NASA DCS/EVA team has the extensive expertise and a wealth of knowledge in this area. The SRP suggests that increased manpower for this team would be highly productive.

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

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

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

Dendritic cell maturation, but not type I interferon exposure, restricts infection by HTLV-1, and viral transmission to T-cells

PubMed Central

Alais, Sandrine; Tanaka, Yuetsu; Journo, Chloé; Mahieux, Renaud; Dutartre, Hélène

2017-01-01

Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively. These different contacts may impact HTLV-1 ability to infect DCs and its subsequent transfer to T-cells. Using in vitro monocyte-derived IL-4 DCs, TGF-β DCs and IFN-α DCs that mimic DCs contacting HTLV-1 in vivo, we show here that despite their increased ability to capture HTLV-1 virions, IFN-α DCs restrict HTLV-1 productive infection. Surprisingly, we then demonstrate that it is not due to the antiviral activity of type–I interferon produced by IFN-α DCs, but that it is likely to be linked to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-α DCs. Finally, we demonstrate that, in contrast to IL-4 DCs, IFN-α DCs are impaired in their capacity to transfer HTLV-1 to CD4 T-cells, both after viral capture and trans-infection and after their productive infection. In conclusion, the nature of the DCs encountered by HTLV-1 upon primo-infection and the viral trafficking route through the vesicular pathway of these cells determine the efficiency of viral transmission to T-cells, which may condition the fate of infection. PMID:28426803

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.

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

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

The ability to monitor one's own memory is an important feature of normal memory and is an aspect of 'metamemory'. Lesion studies have shown dissociations between memory and metamemory, but only single dissociations have been shown using transcranial direct current stimulation (tDCS). One potential reason that only single dissociations have been shown is that tDCS effects may be moderated by task difficulty. We used high definition (HD) tDCS to test for dissociable roles of the dorsolateral prefrontal cortex (DLPFC) and anterior temporal lobe (ATL) in semantic long-term memory and metamemory tasks. We also tested whether general knowledge question difficulty moderated the effects of HD-tDCS. Across 3 sessions, participants received active HD-tDCS over the left DLPFC or left ATL, or sham HD-tDCS during general knowledge recall and recognition tests, and a 'feeling-of-knowing' metamemory task. General knowledge questions were blocked by difficulty. Repeated measures ANOVAs were used to examine the effects of HD-tDCS on memory and metamemory tasks by memory question difficulty. HD-tDCS over the ATL led to improved recall compared to DLPFC and sham HD-tDCS, and this occurred only for medium difficulty questions. In contrast, for non-recalled questions, HD-tDCS over the DLPFC led to improved recognition accuracy and improved feeling-of-knowing accuracy compared to ATL and sham HD-tDCS, and this was not moderated by memory question difficulty. HD-tDCS can be used to dissociate the roles of the ATL and DLPFC in different memory and 'metamemory' tasks. The effects of HD-tDCS on task may be moderated by task difficulty, depending on the nature of the task and site of stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells.

PubMed

Dumitriu, Ingrid E; Dunbar, Donald R; Howie, Sarah E; Sethi, Tariq; Gregory, Christopher D

2009-03-01

Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present in the tumor milieu can alter the maturation of DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human DCs increased the expression of TGF-beta1 transcripts following culture with human lung carcinoma cells (LCCs). These DCs produced increased amounts of TGF-beta1 protein compared with DCs not exposed to tumor cells. LCCs also decreased the expression of CD86 and HLA-DR by immature DCs. Furthermore, LCCs decreased CD86 expression and the production of TNF-alpha and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs into cells producing TGF-beta1. These TGF-beta1-producing DCs were poor at eliciting the activation of naive CD4(+) T cells and sustaining their proliferation and differentiation into Th1 (IFN-gamma(+)) effectors. Instead, TGF-beta1-producing DCs demonstrated an increased ability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress the proliferation of T lymphocytes. These results identify a novel mechanism by which the function of human DCs is altered by tumor cells and contributes to the evasion of the immune response.

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

PubMed

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

2008-03-01

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

Reduction of conventional dendritic cells during Plasmodium infection is dependent on activation induced cell death by type I and II interferons.

PubMed

Tamura, Takahiko; Kimura, Kazumi; Yui, Katsuyuki; Yoshida, Shigeto

2015-12-01

Dendritic cells (DCs) play critical roles in innate and adaptive immunity and in pathogenesis during the blood stage of malaria infection. The mechanisms underlying DC homeostasis during malaria infection are not well understood. In this study, the numbers of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the spleens after lethal rodent malaria infection were examined, and were found to be significantly reduced. Concomitant with up-regulation of maturation-associated molecules, activation of caspase-3 was significantly increased, suggesting induction of cell death. Studies using neutralizing antibody and gene-deficient mice showed that type I and II interferons were critically involved in activation induced cell death of cDCs during malaria infection. These results demonstrate that DCs rapidly disappeared following IFN-mediated DC activation, and that homeostasis of DCs was significantly impaired during malaria infection. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

PubMed

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

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

Effects of prefrontal bipolar and high-definition transcranial direct current stimulation on cortical reactivity and working memory in healthy adults.

PubMed

Hill, Aron T; Rogasch, Nigel C; Fitzgerald, Paul B; Hoy, Kate E

2017-05-15

Transcranial direct current stimulation (tDCS) is a well-recognised neuromodulatory technology which has been shown to induce short-lasting changes in motor-cortical excitability. The recent and rapid expansion of tDCS into the cognitive domain, however, necessitates deeper mechanistic understanding of its neurophysiological effects over non-motor brain regions. The present study utilised transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to probe the immediate and longer-term effects of both a bipolar (BP-tDCS) and more focal 4×1 High-Definition tDCS (HD-tDCS) montage applied over the left DLPFC on TMS-evoked potentials (TEPs) and oscillations in 19 healthy adult participants. 2-back working memory (WM) performance was also assessed as a marker of cognitive function. Region of interest (ROI) analyses taken from the F1 electrode directly adjacent to the stimulation site revealed increased P60 TEP amplitudes at this location 5min following BP-tDCS and 30min following HD-tDCS. Further global cluster based analyses of all scalp electrodes revealed widespread neuromodulatory changes following HD-tDCS, but not BP-tDCS, both five and 30min after stimulation, with reductions also detected in both beta and gamma oscillatory power over parieto-occipital channels 30min after stimulation. No significant changes in WM performance were observed following either HD-tDCS or BP-tDCS. This study highlights the capacity for single-session prefrontal anodal tDCS montages to modulate neurophysiological processes, as assessed with TMS-EEG. Copyright © 2017 Elsevier Inc. All rights reserved.

Superficial ovarian cortex vascularization is inversely related to the follicle reserve in normal cycling ovaries and is increased in polycystic ovary syndrome.

PubMed

Delgado-Rosas, F; Gaytán, M; Morales, C; Gómez, R; Gaytán, F

2009-05-01

The superficial ovarian cortex constitutes the micro-environment where resting and early growing follicles reside. As small follicles do not possess an independent capillary network, both their survival and early growth depend on their proximity to the cortical vessels. Little is known about the possible changes in superficial ovarian cortex vascularization in normal women throughout reproductive life or in pathological conditions such as polycystic ovary syndrome (PCOS) involving abnormal early follicle growth. We studied the vascularization of the superficial and deep cortical stroma (DCS) in normal cycling ovaries from 21 to 50 years of age and in infertile women with PCOS. We used archival ovarian samples and specific CD34 immunostaining to determine blood vessel density and to analyse correlation with age and with the ovarian follicle reserve. Normal cycling ovaries showed an age-related increase in the superficial cortical stroma vascularization that was inversely correlated with the density of small (primordial and primary) follicles. In contrast, blood vessel density in the DCS significantly decreased in women aged >or=40 years. Ovaries from PCOS showed a 2-fold increase in blood vessel density in both superficial cortical stroma and DCS with respect to age-matched controls. The increased vascularization of the superficial cortical stroma in normal ovaries in relation to age and in ovaries from PCOS could have profound effects on cortical metabolic rate, primordial follicle survival/activation and early follicle growth, and may underline changes in follicle dynamics in mid-aged women and in PCOS.

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.

Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25.

PubMed

Li, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Chang, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

2015-12-15

This study was to investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-κB in DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-κB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-κB expression of DCs. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF-κB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and NF-κB expression in DCs stimulated by TNF-alpha. These results demonstrate that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice

PubMed Central

Lutz, Manfred B.; Zernecke, Alma

2014-01-01

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr −/−) mice, CD11c+ MHCII+ DCs could be discriminated into CD103− CD11b+F4/80+, CD11b+F4/80− and CD11b−F4/80− DCs and CD103+ CD11b−F4/80− DCs. Except for CD103− CD11b− F4/80− DCs, these subsets expanded in high fat diet-fed Ldlr −/− mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103− CD11b− F4/80− but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l −/−) mice, a specific loss of CD103+ DCs but also CD103− CD11b+ F4/80− DCs was evidenced. Aortic CD103+ and CD11b+ F4/80− CD103− DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103− CD11b+ F4/80− and CD11b+ F4/80+ cells in atherosclerotic Ldlr −/− mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/80− DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation. PMID:24551105

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

Downregulation of ILT4+ dendritic cells in recurrent miscarriage and recurrent implantation failure.

PubMed

Liu, Su; Wei, Hongxia; Li, Yuye; Huang, Chunyu; Lian, Ruochun; Xu, Jian; Chen, Lanna; Zeng, Yong

2018-06-14

The role of ILT4 + DCs in healthy fertile controls and patients with recurrent miscarriages (RM) and recurrent implantation failure (RIF) is unclear. We studied the expression of ILT4 from peripheral blood and endometrial samples from healthy controls and patients with RM and RIF by flow cytometry and immunohistochemistry analysis. Endometrial Foxp3 expression was also investigated using immunohistochemistry. In peripheral blood, there was a significant increase in the percentage of ILT4 + DCs in healthy fertile controls compared with patients with RM and RIF. The presence of ILT4 + DC is even more prominent in the endometrium of healthy fertile controls compared with patients with RM and RIF. Moreover, there was a strong correlation between the number of ILT4 + cells and Foxp3 + Tregs in healthy fertile controls, but not in patients with RM and RIF. Our data indicate that ILT4 + DCs play an important role in the maintenance of immune tolerance during pregnancy, probably through the induction of Foxp3 + Treg cells, a process which is impaired in RM and RIF. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans.

PubMed

Mizuguchi, Nobuaki; Uehara, Shintaro; Hirose, Satoshi; Yamamoto, Shinji; Naito, Eiichi

2016-01-01

Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.

Medial prefrontal cortex reacts to unfairness if this damages the self: a tDCS study

PubMed Central

Miniussi, Carlo; Rumiati, Raffaella I.

2015-01-01

Neural correlates of unfairness perception depend on who is the target of the unfair treatment. These previous findings suggest that the activation of medial prefrontal cortex (MPFC) is related to unfairness perception only when the subject of the measurement is also the person affected by the unfair treatment. We aim at demonstrating the specificity of MPFC involvement using transcranial direct current stimulation (tDCS), a technique that induces cortical excitability changes in the targeted region. We use a modified version of the Ultimatum Game, in which responders play both for themselves (myself—MS condition) and on behalf of an unknown third-party (TP condition), where they respond to unfairness without being the target of it. We find that the application of cathodal tDCS over MPFC decreases the probability of rejecting unfair offers in MS, but not in TP; conversely, the same stimulation increases the probability of rejecting fair offers in TP, but not in MS. We confirm the hypothesis that MPFC is specifically related to processing unfairness when the self is involved, and discuss possible explanations for the opposite effect of the stimulation in TP. PMID:25552567

Soluble TNF receptor 1-secreting ex vivo-derived dendritic cells reduce injury after stroke.

PubMed

Works, Melissa G; Koenig, Jenny B; Sapolsky, Robert M

2013-09-01

Inflammation is a major factor in the progression of damage after stroke and in the clinic, current therapies treat the clot, not the resulting damage. We have developed a novel method of protein delivery that exploits the migration ability of leukocytes after ischemic stroke (transient middle cerebral artery occlusion; tMCAO). In our studies, ex vivo-derived dendritic cells (exDCs) migrate to the inflamed rat brain soon after tMCAO onset and the number of cells that remain in the brain after injection is significantly correlated with the amount of local inflammation at the injury site. In addition, exDCs transduced to overexpress soluble tumor necrosis factor (TNF) receptor1 (sTNFR1) produce functional cargo that is secreted and that blocks TNF-α bioavailability in vitro. When delivered at 6 hours post-tMCAO reperfusion, sTNFR1-exDC-treated rats show significantly smaller infarct size and decreased inflammation compared with animals treated with exDCs transduced with GFP lentivirus. These studies indicate that cell-mediated delivery of proteins may be a promising new approach to reduce brain damage after acute neurologic insult.

Novel methods to optimize the effects of transcranial direct current stimulation: a systematic review of transcranial direct current stimulation patents.

PubMed

Malavera, Alejandra; Vasquez, Alejandra; Fregni, Felipe

2015-01-01

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has been extensively studied. While there have been initial positive results in some clinical trials, there is still variability in tDCS results. The aim of this article is to review and discuss patents assessing novel methods to optimize the use of tDCS. A systematic review was performed using Google patents database with tDCS as the main technique, with patents filling date between 2010 and 2015. Twenty-two patents met our inclusion criteria. These patents attempt to address current tDCS limitations. Only a few of them have been investigated in clinical trials (i.e., high-definition tDCS), and indeed most of them have not been tested before in human trials. Further clinical testing is required to assess which patents are more likely to optimize the effects of tDCS. We discuss the potential optimization of tDCS based on these patents and the current experience with standard tDCS.

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.

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

PubMed Central

Vaseghi, Bita; Zoghi, Maryam; Jaberzadeh, Shapour

2015-01-01

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

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.

Polarization effects in low-energy electron-CH4 elastic collisions in an exact exchange treatment

NASA Astrophysics Data System (ADS)

Jain, Ashok; Weatherford, C. A.; Thompson, D. G.; McNaughten, P.

1989-12-01

We have investigated the polarization effects in very-low-energy (below 1 eV) electron- CH4 collisions in an exact-exchange treatment. The two models of the parameter-free polarization potential are employed; one, the VpolJT potential, introduced by Jain and Thompson [J. Phys. B 15, L631 (1982)], is based on an approximate polarized-orbital method, and two, the correlation-polarization potential VpolCP, first proposed by O'Connel and Lane [Phys. Rev. A 27, 1893 (1983)], is given as a simple analytic form in terms of the charge density of the target. In this rather very low-energy region, the polarization effects play a decisive role, particularly in creating structure in the differential cross section (DCS) and producing the Ramsauer-Townsend minimum in the total cross section. Our DCS at 0.2, 0.4, and 0.6 eV are compared with recent measurements. We found that a local parameter-free approximation for the polarization potential is quite successful if it is determined under the polarized-orbital-type technique rather than based on the correlation-polarization approach.

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.

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.

Early adopters of the magical thinking cap: a study on do-it-yourself (DIY) transcranial direct current stimulation (tDCS) user community

PubMed Central

Jwa, Anita

2015-01-01

Among currently available technologies, transcranial direct current stimulation (tDCS) is one of the most promising neuroenhancements because it is relatively effective, safe, and affordable. Recently, lay people have begun to build—or purchase—the tDCS device to use it at home for treatment or as a cognitive enhancer. The tDCS device is currently not covered by the existing regulatory framework, but there are still significant potential risks of misusing this device, and its long-term effects on the brain have not been fully explored. Thus, researchers have argued the need for regulations or official guidelines for the personal use of tDCS. However, until now, no systematic research on the do-it-yourself (DIY) tDCS user community has been done. The present study explores the basic demographic characteristics of DIY tDCS users as well as why and how they are using this device through a questionnaire survey, in-depth interviews, and a content analysis of web postings on the use of tDCS. This preliminary but valuable picture of the DIY tDCS user community will shed light on future studies and policy analysis to craft sound regulations and official guidelines for the use of tDCS. PMID:27774197

Early adopters of the magical thinking cap: a study on do-it-yourself (DIY) transcranial direct current stimulation (tDCS) user community.

PubMed

Jwa, Anita

2015-07-01

Among currently available technologies, transcranial direct current stimulation (tDCS) is one of the most promising neuroenhancements because it is relatively effective, safe, and affordable. Recently, lay people have begun to build-or purchase-the tDCS device to use it at home for treatment or as a cognitive enhancer. The tDCS device is currently not covered by the existing regulatory framework, but there are still significant potential risks of misusing this device, and its long-term effects on the brain have not been fully explored. Thus, researchers have argued the need for regulations or official guidelines for the personal use of tDCS. However, until now, no systematic research on the do-it-yourself (DIY) tDCS user community has been done. The present study explores the basic demographic characteristics of DIY tDCS users as well as why and how they are using this device through a questionnaire survey, in-depth interviews, and a content analysis of web postings on the use of tDCS. This preliminary but valuable picture of the DIY tDCS user community will shed light on future studies and policy analysis to craft sound regulations and official guidelines for the use of tDCS.

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 (\

Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity

PubMed Central

Khan, Nargis; Aqdas, Mohammad; Vidyarthi, Aurobind; Negi, Shikha; Pahari, Susanta; Agnihotri, Tapan; Agrewala, Javed N.

2016-01-01

Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naïve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αβ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens. PMID:27265209

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

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

PubMed Central

Lefebvre, Stephanie; Liew, Sook-Lei

2017-01-01

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

Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

PubMed Central

Omosun, Yusuf; McKeithen, Danielle; Ryans, Khamia; Kibakaya, Caroline; Blas-Machado, Uriel; Li, Duo; Singh, Rajesh; Inoue, Koichi; Xiong, Zhi-Gang; Eko, Francis; Black, Carolyn; Igietseme, Joseph

2015-01-01

Interleukin-10 (IL-10) has been implicated in susceptibility to genital chlamydial infection and the development of tubal pathologies. IL-10 limitation also resulted in the rapid elicitation of immune responses against Chlamydia, and decreased levels of IL-10 correlated with protective anti-Chlamydia immunity. To investigate the molecular basis for these effects, we compared the reproductive pathologies and fertility rates in Chlamydia-infected wild-type (WT) and IL-10-knockout (IL-10−/−) mice; we also analyzed the expression of the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, IL-1β production, NLRP3 inflammasome assembly and activation, and the immunostimulatory capacity and apoptotic predilection of Chlamydia-exposed dendritic cells (DCs) from WT and IL-10−/− mice. Our results revealed that, in addition to the rapid clearance of infection, genitally infected IL-10−/− mice were protected from tubal pathologies and infertility, whereas WT (IL-10+/+) mice were not. Chlamydia-pulsed IL-10−/− DCs expressed larger numbers of TLR4/IL-1R molecules and had enhanced IL-1β production. In addition, NLRP3 inflammasome assembly was suppressed in IL-10−/− DCs through the inhibition of the P2X purinoceptor 7 (P2X7) receptor (P2X7R), an ATP-gated ion channel, and a decrease in intracellular Ca2+ levels, which inhibited DC apoptosis. Thus, the potent immunostimulatory capacity of IL-10-deficient DCs is due, at least in part, to the suppression of the intracellular inflammasome assembly, which prevents DC apoptosis, allowing efficient antigen presentation. The results indicate that IL-10 deficiency enables efficient antigen presentation by DCs for rapid and enhanced immune activation against Chlamydia, which results in rapid microbial clearance, which prevents tubal pathologies during infection. Our finding has important implications for the induction of protective immunity against Chlamydia and other infectious and noninfectious diseases by vaccines. PMID:26371131

Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naïve T Cells From Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201

PubMed Central

Waller, Edmund K.; Logan, Brent R.; Harris, Wayne A.C.; Devine, Steven M.; Porter, David L.; Mineishi, Shin; McCarty, John M.; Gonzalez, Corina E.; Spitzer, Thomas R.; Krijanovski, Oleg I.; Linenberger, Michael L.; Woolfrey, Ann; Howard, Alan; Wu, Juan; Confer, Dennis L.; Anasetti, Claudio

2014-01-01

Purpose To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor–mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Patients and Methods Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Results Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8+ T cells (CD8Tns), or naïve CD4+ T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Conclusion Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation. PMID:24982459

Improved survival after transplantation of more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow grafts: results from BMTCTN 0201.

PubMed

Waller, Edmund K; Logan, Brent R; Harris, Wayne A C; Devine, Steven M; Porter, David L; Mineishi, Shin; McCarty, John M; Gonzalez, Corina E; Spitzer, Thomas R; Krijanovski, Oleg I; Linenberger, Michael L; Woolfrey, Ann; Howard, Alan; Wu, Juan; Confer, Dennis L; Anasetti, Claudio

2014-08-01

To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naïve T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naïve CD8(+) T cells (CD8Tns), or naïve CD4(+) T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. Donor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation. © 2014 by American Society of Clinical Oncology.

Dosage Considerations for Transcranial Direct Current Stimulation in Children: A Computational Modeling Study

PubMed Central

Kessler, Sudha Kilaru; Minhas, Preet; Woods, Adam J.; Rosen, Alyssa; Gorman, Casey; Bikson, Marom

2013-01-01

Transcranial direct current stimulation (tDCS) is being widely investigated in adults as a therapeutic modality for brain disorders involving abnormal cortical excitability or disordered network activity. Interest is also growing in studying tDCS in children. Limited empirical studies in children suggest that tDCS is well tolerated and may have a similar safety profile as in adults. However, in electrotherapy as in pharmacotherapy, dose selection in children requires special attention, and simple extrapolation from adult studies may be inadequate. Critical aspects of dose adjustment include 1) differences in neurophysiology and disease, and 2) variation in brain electric fields for a specified dose due to gross anatomical differences between children and adults. In this study, we used high-resolution MRI derived finite element modeling simulations of two healthy children, ages 8 years and 12 years, and three healthy adults with varying head size to compare differences in electric field intensity and distribution. Multiple conventional and high-definition tDCS montages were tested. Our results suggest that on average, children will be exposed to higher peak electrical fields for a given applied current intensity than adults, but there is likely to be overlap between adults with smaller head size and children. In addition, exposure is montage specific. Variations in peak electrical fields were seen between the two pediatric models, despite comparable head size, suggesting that the relationship between neuroanatomic factors and bioavailable current dose is not trivial. In conclusion, caution is advised in using higher tDCS doses in children until 1) further modeling studies in a larger group shed light on the range of exposure possible by applied dose and age and 2) further studies correlate bioavailable dose estimates from modeling studies with empirically tested physiologic effects, such as modulation of motor evoked potentials after stimulation. PMID:24086698

Combining visual rehabilitative training and noninvasive brain stimulation to enhance visual function in patients with hemianopia: a comparative case study.

PubMed

Plow, Ela B; Obretenova, Souzana N; Halko, Mark A; Kenkel, Sigrid; Jackson, Mary Lou; Pascual-Leone, Alvaro; Merabet, Lotfi B

2011-09-01

To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT). A comparative case study assessing feasibility and safety. A controlled laboratory setting. Two patients, both with right hemianopia after occipital stroke damage. METHODS AND OUTCOME MEASUREMENTS: Both patients underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2 sham tDCS with VRT was performed. The primary outcome, visual field border, was defined objectively by using high-resolution perimetry. Secondary outcomes included subjective characterization of visual deficit and functional surveys that assessed performance on activities of daily living. For patient 1, the neural correlates of visual recovery were also investigated, by using functional magnetic resonance imaging. Delivery of combined tDCS with VRT was feasible and safe. High-resolution perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient 1 also showed greater recovery of function in activities of daily living. Contrary to the expectation, patient 2 perceived greater subjective improvement in visual field despite objective high-resolution perimetry results that indicated otherwise. In patient 1, visual function recovery was associated with functional magnetic resonance imaging activity in surviving peri-lesional and bilateral higher-order visual areas. Results of preliminary case comparisons suggest that occipital cortical tDCS may enhance recovery of visual function associated with concurrent VRT through visual cortical reorganization. Future studies may benefit from incorporating protocol refinements such as those described here, which include global capture of function, control for potential confounds, and investigation of underlying neural substrates of recovery. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

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

PubMed

Gözenman, Filiz; Berryhill, Marian E

2016-08-26

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

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

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

PubMed

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

2017-01-01

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

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 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.

No effect of transcranial direct current stimulation of the dorsolateral prefrontal cortex on short-term memory.

PubMed

Wang, Jing; Wen, Jian-Bing; Li, Xiao-Li

2018-01-01

Short-term memory refers to the capacity for holding information in mind for a short period of time with conscious memorization. It is an important ability for daily life and is impaired in several neurological and psychiatric disorders. Anodal transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) was reported to enhance the capability of short-term memory in healthy subjects. However, results were not consistent and what is the possible impact factor is not known. One important factor that may significantly influence the effect of tDCS is the timing of tDCS administration. In order to explore whether tDCS impact short-term memory and the optimal timing of tDCS administration, we applied anodal tDCS to the left DLPFC to explore the modulatory effect of online and off-line tDCS on digit span as well as visual short-term memory performance in healthy subjects. Results showed tDCS of the left DLPFC did not influence intentional digit span memory performance, whether before the task or during the task. In addition, tDCS of the DLPFC administered before the task showed no effect on visual short-term memory, while there was a trend of increase in false alarm when tDCS of the DLPFC administered during the task. These results did not provide evidence for the enhancement of short-term memory by tDCS of the left DLPFC in healthy subjects, but it suggested an importance of administration time for visual short-term memory. Further studies are required to taking into account the baseline performance of subjects and time-dependence feature of tDCS. © 2017 John Wiley & Sons Ltd.

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).

Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen, by human dendritic cells.

PubMed

Deslée, Gaëtan; Charbonnier, Anne-Sophie; Hammad, Hamida; Angyalosi, Gerhild; Tillie-Leblond, Isabelle; Mantovani, Alberto; Tonnel, André-Bernard; Pestel, Joël

2002-11-01

Immature dendritic cells (DCs) take up antigens in peripheral tissues and, after antigen processing, mature to efficiently stimulate T cells in secondary lymph nodes. In allergic airway diseases DCs have been shown to be involved in the induction and maintenance of a T(H)2-type profile. The present study was undertaken to determine pathways of Der p 1 (a house dust mite allergen) uptake by human DCs and to compare Der p 1 uptake between DCs from patients with house dust mite allergy and DCs from healthy donors. Monocyte-derived DCs (MD-DCs) were obtained from patients with house dust mite allergy (n = 13) and healthy donors (n = 11). Der p 1 was labeled with rhodamine. Der p 1 uptake by MD-DCs was analyzed by means of flow cytometry and confocal microscopy. Rhodamine- labeled Der p 1 was demonstrated to be taken up by MD-DCs in a dose-, time-, and temperature- dependent manner. The involvement of the mannose receptor (MR) in the Der p 1 uptake was demonstrated by using (1) inhibitors of the MR- mediated endocytosis (mannan and blocking anti-MR mAb), which inhibited the Der p 1 uptake from 40 % to 50 %, and (2) confocal microscopy showing the colocalization of rhodamine-labeled Der p 1 with FITC-dextran. Interestingly, compared with DCs from healthy donors, DCs from allergic patients expressed more MR and were more efficient in Der p 1 uptake. These results suggest that the MR could play a key role in the Der p 1 allergen uptake by DCs and in the pathogenesis of allergic diseases in dust mite -sensitive patients.

Direct regulatory immune activity of lactic acid bacteria on Der p 1-pulsed dendritic cells from allergic patients.

PubMed

Pochard, Pierre; Hammad, Hamida; Ratajczak, Céline; Charbonnier-Hatzfeld, Anne-Sophie; Just, Nicolas; Tonnel, André-Bernard; Pestel, Joël

2005-07-01

Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1-pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1-pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1-pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1-pulsed DCs. Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.

Treatment with direct-current stimulation against cingulate seizure-like activity induced by 4-aminopyridine and bicuculline in an in vitro mouse model.

PubMed

Chang, Wei-Pang; Lu, Hsiang-Chin; Shyu, Bai-Chuang

2015-03-01

Clinical studies have shown that cathodal transcranial direct-current stimulation (tDCS) application can produce long-term suppressive effects on drug-resistant seizures. Whether this long-term effect produced by cathodal tDCS can counterbalance the enhancement of synaptic transmission during seizures requires further investigation. Our hypothesis was that the long-term effects of DCS on seizure suppression by the application of cathodal DCS occur through a long-term depression (LTD)-like mechanism. We used a thalamocingulate brain slice preparation combined with a multielectrode array and patch recording to investigate the underlying mechanism of the suppressive effect of DCS on anterior cingulate cortex (ACC) seizures. Patch-clamp recordings showed that cathodal DCS significantly decreased spontaneous excitatory postsynaptic currents (EPSCs) and epileptic EPSCs caused by the 4-aminopyridine. Fifteen minutes of DCS application reliably induced LTD, and the synaptic activation frequency was an important factor in LTD formation. The application of DCS alone without continuous synaptic activation did not induce LTD. Direct-current stimulation-induced LTD appeared to be N-methyl-d-aspartate (NMDA)-dependent, in which the application of the NMDA receptor antagonist D-1-2-amino-5-phosphonopentanoic acid (APV) abolished DCS-induced LTD, and the immediate effect remained. Direct-current stimulation-induced LTD and the long-term effects of DCS on seizure-like activities were also abolished by okadaic acid, a protein phosphatase 1 inhibitor. The long-term effects of DCS on seizures were not influenced by the depotentiation blocker FK-506. Therefore, we conclude that the long-term effects of DCS on seizure-like activities in brain slice occur through an LTD-like mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-15

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

CD40 ligation and phagocytosis differently affect the differentiation of monocytes into dendritic cells.

PubMed

Rosenzwajg, Michelle; Jourquin, Frédéric; Tailleux, Ludovic; Gluckman, Jean Claude

2002-12-01

That monocytes can differentiate into macrophages or dendritic cells (DCs) makes them an essential link between innate and adaptive immunity. However, little is known about how interactions with pathogens or T cells influence monocyte engagement toward DCs. We approached this point in cultures where granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 induced monocytes to differentiate into immature DCs. Activating monocytes with soluble CD40 ligand (CD40L) led to accelerated differentiation toward mature CD83(+) DCs with up-regulated human leukocyte antigen-DR, costimulatory molecules and CD116 (GM-CSF receptor), and down-regulation of molecules involved in antigen capture. Monocytes primed by phagocytosis of antibody-opsonized, killed Escherichia coli differentiated into DCs with an immature phenotype, whereas Zymosan priming yielded active DCs with an intermediate phenotype. Accordingly, DCs obtained from cultures with CD40L or after Zymosan priming had a decreased capacity to endocytose dextran, but only DCs cultured with CD40L had increased capacity to stimulate allogeneic T cells. DCs obtained after E. coli or Zymosan priming of monocytes produced high levels of proinflammatory tumor necrosis factor alpha and IL-6 as well as of regulatory IL-10, but they produced IL-12p70 only after secondary CD40 ligation. Thus, CD40 ligation on monocytes accelerates the maturation of DCs in the presence of GM-CSF/IL-4, whereas phagocytosis of different microorganisms does not alter and even facilitates their potential to differentiate into immature or active DCs, the maturation of which can be completed upon CD40 ligation. In vivo, such differences may correspond to DCs with different trafficking and T helper cell-stimulating capacities that could differently affect induction of adaptive immune responses to infections.

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.

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

PubMed

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

2013-11-01

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

Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells.

PubMed

Van Acker, Heleen H; Beretta, Ottavio; Anguille, Sébastien; De Caluwé, Lien; Papagna, Angela; Van den Bergh, Johan M; Willemen, Yannick; Goossens, Herman; Berneman, Zwi N; Van Tendeloo, Viggo F; Smits, Evelien L; Foti, Maria; Lion, Eva

2017-02-21

Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8+ T cells, natural killer (NK) cells and gamma delta (γδ) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B+ effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated γδ T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.

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.

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.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

PubMed

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-11-15

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans

PubMed Central

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-01-01

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications. PMID:12949224

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.

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

PubMed

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

2016-12-01

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

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

PubMed Central

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

2016-01-01

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. PMID:26455796

Effects of 12C6+ Heavy Ion Radiation on Dendritic Cells Function

PubMed Central

Zhang, Pei; Hu, Xuguang; Liu, Bin; Liu, Zhe; Liu, Cong; Cai, Jianming; Gao, Fu; Li, Bailong

2018-01-01

Background Carbon ion radiotherapy has been shown to be more effective in cancer radiotherapy than photon irradiation. Influence of carbon ion radiation on cancer microenvironment is very important for the outcomes of radiotherapy. Tumor-infiltrating dendritic cells (DCs) play critical roles in cancer antigen processing and antitumor immunity. However, there is scant literature covering the effects of carbon ion radiation on DCs. In this study, we aimed to uncover the impact of carbon ion irradiation on bone marrow derived DCs. Material/Methods Bone marrow cells were co-cultured with GM-CSF and IL-4 for seven days, and the population of DCs was confirmed with flow cytometry. We used an Annexin V and PI staining method to detect cell apoptosis. Endocytosis assay of DCs was determined by using a flow cytometry method. DCs migration capacity was tested by a Transwell method. We also used ELISA assay and western blotting assay to examine the cytokines and protein expression, respectively. Results Our data showed that carbon ion radiation induced apoptosis in both immature and mature DCs. After irradiation, the endocytosis and migration capacity of DCs was also impaired. Interestingly, carbon irradiation triggered a burst of IFN-γ and IL-12 in LPS or CpG treated DCs, which provide novel insights into the combination of immunotherapy and carbon ion radiotherapy. Finally, we found that carbon ion irradiation induced apoptosis and migration suppression was p38 dependent. Conclusions Our present study demonstrated that carbon ion irradiation induced apoptosis in DCs, and impaired DCs function mainly through the p38 signaling pathway. Carbon ion irradiation also triggered anti-tumor cytokines secretion. This work provides novel information of carbon ion radiotherapy in DCs, and also provides new insights on the combination of immune adjuvant and carbon ion radiotherapy. PMID:29525808

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…

Effect of oxygen levels on the physiology of dendritic cells: implications for adoptive cell therapy.

PubMed

Futalan, Diahnn; Huang, Chien-Tze; Schmidt-Wolf, Ingo G H; Larsson, Marie; Messmer, Davorka

2011-01-01

Dendritic cell (DC)-based adoptive tumor immunotherapy approaches have shown promising results, but the incidence of tumor regression is low and there is an evident call for identifying culture conditions that produce DCs with a more potent Th1 potential. Routinely, DCs are differentiated in CO(2) incubators under atmospheric oxygen conditions (21% O(2)), which differ from physiological oxygen levels of only 3-5% in tissue, where most DCs reside. We investigated whether differentiation and maturation of DCs under physiological oxygen levels could produce more potent T-cell stimulatory DCs for use in adoptive immunotherapy. We found that immature DCs differentiated under physiological oxygen levels showed a small but significant reduction in their endocytic capacity. The different oxygen levels did not influence their stimuli-induced upregulation of cluster of differentiation 54 (CD54), CD40, CD83, CD86, C-C chemokine receptor type 7 (CCR7), C-X-C chemokine receptor type 4 (CXCR4) and human leukocyte antigen (HLA)-DR or the secretion of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 in response to lipopolysaccharide (LPS) or a cytokine cocktail. However, DCs differentiated under physiological oxygen level secreted higher levels of IL-12(p70) after exposure to LPS or CD40 ligand. Immature DCs differentiated at physiological oxygen levels caused increased T-cell proliferation, but no differences were observed for mature DCs with regard to T-cell activation. In conclusion, we show that although DCs generated under atmospheric or physiological oxygen conditions are mostly similar in function and phenotype, DCs differentiated under physiological oxygen secrete larger amounts of IL-12(p70). This result could have implications for the use of ex vivo-generated DCs for clinical studies, since DCs differentiated at physiological oxygen could induce increased Th1 responses in vivo.

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.

Feasibility and Clinical Utility of High-definition Transcranial Direct Current Stimulation in the Treatment of Persistent Hallucinations in Schizophrenia.

PubMed

Bose, A; Shivakumar, V; Chhabra, H; Parlikar, R; Sreeraj, V S; Dinakaran, D; Narayanaswamy, J C; Venkatasubramanian, G

2017-12-01

Persistent auditory verbal hallucination is a clinically significant problem in schizophrenia. Recent studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in treatment. An optimised version of tDCS, namely high-definition tDCS (HD-tDCS), uses smaller electrodes arranged in a 4x1 ring configuration and may offer more focal and predictable neuromodulation than conventional tDCS. This case report illustrates the feasibility and clinical utility of add-on HD-tDCS over the left temporoparietal junction in a 4x1 ring configuration to treat persistent auditory verbal hallucination in schizophrenia.

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.

Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa).

PubMed

Krasovsky, Joseph; Chang, David H; Deng, Gary; Yeung, Simon; Lee, Mavis; Leung, Ping Chung; Cunningham-Rundles, Susanna; Cassileth, Barrie; Dhodapkar, Madhav V

2009-03-01

Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic "supercritical" extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions.

Inhibition of Human Dendritic Cell Activation by Hydroethanolic But Not Lipophilic Extracts of Turmeric (Curcuma longa)

PubMed Central

Krasovsky, Joseph; Chang, David H.; Deng, Gary; Yeung, Simon; Lee, Mavis; Leung, Ping Chung; Cunningham-Rundles, Susanna; Cassileth, Barrie; Dhodapkar, Madhav V.

2015-01-01

Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic “supercritical” extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions. PMID:19034830

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

PubMed Central

Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

2012-01-01

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

Diesel Exhaust Exposure Increases Susceptibility to Influenza ...

EPA Pesticide Factsheets

Mice were necropsied at day 1, 4, 8 and 14 post-infection and lung tissue was assessed for virus titers by TCID50, lung injury and inflammation. Lung and lymph node DC populations (CD11c+, MHCII, CD45+, CD80+ and CD86+) were identified by flow cytometry. Prior exposure to DE significantly increased viral titers in the lung at 4 and 8 days post infection in association with increased neutrophil influx and lung injury. Pro-inflammatory cytokines including IP-10, MCP-1, GM-CSF, and IL-1β, and the antiviral cytokine IFN-β were also increased at days 1, 4 and 8 post infection compared to air/flu controls. The number of DCs in the lung was not affected with previous exposure to DE, however the lymph nodes had increased number of mature DCs at 1, 4, and 8 days post infection compared to the air/flu controls. We conclude that exposure to DE prior to an influenza infection increases pulmonary inflammation, viral titers, and stimulates more DCs to migrate to the lymph nodes and mature as a consequence of the DE-enhanced influenza infection. Numerous studies have shown that diesel exhaust (DE) decreases resistance to respiratory infection and can alter the maturation and migration of dendritic cells (DCs). The purpose of this study was to evaluate the effects of DE exposure on susceptibilty to influenza infection in mice and to determine if this correlated with changes in the pulmonary DC populations. BALB/c mice were exposed to air or 0.5 mg/m3 DE from a diesel-power

A novel CD4-CD8alpha+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis.

PubMed

Ruiz, Sophie; Beauvillain, Céline; Mévélec, Marie-Noëlle; Roingeard, Philippe; Breton, Pascal; Bout, Daniel; Dimier-Poisson, Isabelle

2005-11-01

Dendritic cells (DCs) play an essential role in the induction of immune responses to pathogen infections. Native DCs are difficult to obtain in large numbers and consequently the vast majority of DCs employed in all experiments are derived from bone marrow progenitors. In an attempt to solve this problem, we have established a novel CD8alpha(+) DC line (H-2(k)) from spleen, which we have named SRDC line, and which is easy to culture in vitro. These cells display similar morphology, phenotype and activity to CD4(-)CD8alpha(+)CD205(+)CD11b(-) DCs purified ex vivo. Toxoplasma gondii antigen was shown to be taken up by these cells and to increase class I and class II major histocompatibility complex (MHC), CD40, CD80 and CD86 surface expression. We report that vaccination with T. gondii antigen-pulsed SRDCs, which synthesize large amounts of interleukin-12, induced protective immune responses against this intracellular pathogen in syngeneic CBA/J mice. This protection was associated with strong cellular and humoral immune responses at systemic and intestinal levels. Spleen and mesenteric lymph node cell proliferations were correlated with a Th1/Th2-type response and a specific SRDC homing to spleen and intestine was observed. The SRDC or CD4(-)CD8alpha(+)CD205(+)CD11b(-) DC line can be expected to be a very useful tool for immunobiology studies of DC.

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

PubMed

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

2016-01-01

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

An optimized two-photon method for in vivo lung imaging reveals intimate cell collaborations during infection

NASA Astrophysics Data System (ADS)

Fiole, Daniel; Deman, Pierre; Trescos, Yannick; Douady, Julien; Tournier, Jean-Nicolas

2013-02-01

Lung tissue motion arising from breathing and heart beating has been described as the largest annoyance of in vivo imaging. Consequently, infected lung tissue has never been imaged in vivo thus far, and little is known concerning the kinetics of the mucosal immune system at the cellular level. We have developed an optimized post-processing strategy to overcome tissue motion, based upon two-photon and second harmonic generation (SHG) microscopy. In contrast to previously published data, we have freed the lung parenchyma from any strain and depression in order to maintain the lungs under optimal physiological parameters. Excitation beams swept the sample throughout normal breathing and heart movements, allowing the collection of many images. Given that tissue motion is unpredictably, it was essential to sort images of interest. This step was enhanced by using SHG signal from collagen as a reference for sampling and realignment phases. A normalized cross-correlation criterion was used between a manually chosen reference image and rigid transformations of all others. Using CX3CR1+/gfp mice this process allowed the collection of high resolution images of pulmonary dendritic cells (DCs) interacting with Bacillus anthracis spores, a Gram-positive bacteria responsible for anthrax disease. We imaged lung tissue for up to one hour, without interrupting normal lung physiology. Interestingly, our data revealed unexpected interactions between DCs and macrophages, two specialized phagocytes. These contacts may participate in a better coordinate immune response. Our results not only demonstrate the phagocytizing task of lung DCs but also infer a cooperative role of alveolar macrophages and DCs.

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

Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex.

PubMed

Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Cipolotti, Lisa; Oliveri, Massimiliano

2015-01-01

The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task. 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS. Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance. Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects.

Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

PubMed Central

Holmes, Ben; Jung, Seung Ho; Lu, Jing; Wagner, Jessica A.; Rubbi, Liudmilla; Pellegrini, Matteo

2016-01-01

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied. PMID:28119786

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

PubMed

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

2012-05-01

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

Type I interferon dependence of plasmacytoid dendritic cell activation and migration

PubMed Central

Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio

2005-01-01

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237

Differential effects of bifrontal and occipital nerve stimulation on pain and fatigue using transcranial direct current stimulation in fibromyalgia patients.

PubMed

To, Wing Ting; James, Evan; Ost, Jan; Hart, John; De Ridder, Dirk; Vanneste, Sven

2017-07-01

Fibromyalgia is a disorder characterized by widespread musculoskeletal pain frequently accompanied by other symptoms such as fatigue. Moderate improvement from pharmacological and non-pharmacological treatments have proposed non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to the occipital nerve (more specifically the C2 area) or to the dorsolateral prefrontal cortex (DLPFC) as potential treatments. We aimed to explore the effectiveness of repeated sessions of tDCS (eight sessions) targeting the C2 area and DLPFC in reducing fibromyalgia symptoms, more specifically pain and fatigue. Forty-two fibromyalgia patients received either C2 tDCS, DLPFC tDCS or sham procedure (15 C2 tDCS-11 DLPFC tDCS-16 sham). All groups were treated with eight sessions (two times a week for 4 weeks). Our results show that repeated sessions of C2 tDCS significantly improved pain, but not fatigue, in fibromyalgia patients, whereas repeated sessions of DLPFC tDCS significantly improved pain as well as fatigue. This study shows that eight sessions of tDCS targeting the DLPFC have a more general relief in fibromyalgia patients than when targeting the C2 area, suggesting that stimulating different targets with eight sessions of tDCS can lead to benefits on different symptom dimensions of fibromyalgia.

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

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

A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception.

PubMed

Borckardt, Jeffrey J; Bikson, Marom; Frohman, Heather; Reeves, Scott T; Datta, Abhishek; Bansal, Varun; Madan, Alok; Barth, Kelly; George, Mark S

2012-02-01

Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain. Copyright © 2012. Published by Elsevier Inc.

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

PubMed

Westwood, Samuel J; Romani, Cristina

2017-09-01

Recent reviews quantifying the effects of single sessions of transcranial direct current stimulation (or tDCS) in healthy volunteers find only minor effects on cognition despite the popularity of this technique. Here, we wanted to quantify the effects of tDCS on language production tasks that measure word reading and picture naming. We reviewed 14 papers measuring tDCS effects across a total of 96 conditions to a) quantify effects of conventional stimulation on language regions (i.e., left hemisphere anodal tDCS administered to temporal/frontal areas) under normal conditions or under conditions of cognitive (semantic) interference; b) identify parameters which may moderate the size of the tDCS effect within conventional stimulation protocols (e.g., online vs offline, high vs. low current densities, and short vs. long durations), as well as within types of stimulation not typically explored by previous reviews (i.e., right hemisphere anodal tDCS or left/right hemisphere cathodal tDCS). In all analyses there was no significant effect of tDCS, but we did find a small but significant effect of time and duration of stimulation with stronger effects for offline stimulation and for shorter durations (< 15min). We also found some indication of publication bias towards reporting positive effects. We encourage further experimentation in order resolve the disparity between the current popularity of tDCS and its poor efficacy in healthy participants. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells

PubMed Central

Poulin, Lionel Franz; Salio, Mariolina; Griessinger, Emmanuel; Anjos-Afonso, Fernando; Craciun, Ligia; Chen, Ji-Li; Keller, Anna M.; Joffre, Olivier; Zelenay, Santiago; Nye, Emma; Le Moine, Alain; Faure, Florence; Donckier, Vincent; Sancho, David; Cerundolo, Vincenzo; Bonnet, Dominique

2010-01-01

In mouse, a subset of dendritic cells (DCs) known as CD8α+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8α+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8α+ DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8α+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8α+ DCs) TLR9. DNGR-1+ BDCA3hi DCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell–derived signals. Notably, DNGR-1+ BDCA3+ DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I:C. The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy. PMID:20479117

B Physics, Hg EDM, and Lepton Flavor Violation in SUSY Models

NASA Astrophysics Data System (ADS)

Shimizu, Yasuhiro

2005-06-01

We consider the correlation between the CP asymmetry in B → ϕKs (SϕKs) and the chromoelectric dipole moment (CEDM) of strange quark (dCs), which is constrained by the electric dipole moment (EDM) of 199Hg, is studied in the SUSY SU(5) GUT with right-handed neutrinos.

The detailed analysis of the changes of murine dendritic cells (DCs) induced by thymic peptide

PubMed Central

Hu, Xiaofang; Zheng, Wei; Wang, Lu; Wan, Nan; Wang, Bing; Li, Weiwei; Hua, Hui; Hu, Xu; Shan, Fengping

2012-01-01

The aim of present research is to analyze the detailed changes of dendritic cells (DCs) induced by pidotimod(PTD). These impacts on DCs of both bone marrow derived DCs and established DC2.4 cell line were assessed with use of conventional scanning electron microscopy (SEM), flow cytometry (FCM), transmission electron microscopy (TEM), cytochemistry assay FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA). We demonstrated the ability of PTD to induce DC phynotypic and functional maturation as evidenced by higher expression of key surface molecules such as MHC II, CD80 and CD86. The functional tests proved the downregulation of ACP inside the DCs, occurred when phagocytosis of DCs decreased, with simultaneously antigen presentation increased toward maturation. Finally, PTD also stimulated production of more cytokine IL-12 and less TNF-α. Therefore it is concluded that PTD can markedly exert positive induction to murine DCs. PMID:22863756

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2012-10-01

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

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified Aromatic-Turmerone (AR)

PubMed Central

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

2012-01-01

The aim of this work is to evaluate the effects of purified aromatic-turmerone(ar-turmerione, AR) on murine dendritic cells (DCs). These impacts of AR on DCs from bone marrow derived DCs(BMDCs) were assessed with use of conventional scanning electron microscopy (SEM), fluorescence activated cell sorting (FACS), transmission electron microscopy (TEM), cytochemistry assay, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA). We found that AR induced phenotypic maturation as evidenced by increased expression of CD86, CD40, CD83, CD80 and major histocompatibility complex II (MHC II). The functional tests showed the activity of acidic phosphatase (ACP) inside the DCs were downregulated after treatment with AR (which occurs when phagocytosis of DCs were decreased). Finally, we proved that AR increased the production of IL-12 and tumor necrosis factor α (TNF-α). These data suggested that AR could promote phenotypic and functional maturation of DCs and this adjuvant-like activity may have potential therapeutic value. It is therefore concluded that AR could exert positive modulation on murine DCs. PMID:23095866

Vinpocetine Inhibited the CpG Oligodeoxynucleotide-induced Immune Response in Plasmacytoid Dendritic Cells.

PubMed

Feng, Xungang; Wang, Yuzhong; Hao, Yanlei; Ma, Qun; Dai, Jun; Liang, Zhibo; Liu, Yantao; Li, Xiangyuan; Song, Yan; Si, Chuanping

2017-04-01

Plasmacytoid dendritic cells (pDCs) exert dual roles in immune responses through inducing inflammation and maintaining immune tolerance. A switch of pDC phenotype from pro-inflammation to tolerance has therapeutic promise in the treatment of autoimmune diseases. Vinpocetine, a vasoactive vinca alkaloid extracted from the periwinkle plant, has recently emerged as an immunomodulatory agent. In this study, we evaluated the effect of vinpocetine on phenotype of pDCs isolated from C57BL/6 mice and explored its possible mechanism. Our data showed that vinpocetine significantly downregulated the expression of CD40, CD80, and CD86 on pDCs and increased the expression of translocator protein (TSPO), the specific receptor of vinpocetine, in pDCs. Vinpocetine significantly inhibited the Toll-like receptor 9 signaling pathway and reduced the secretion of related cytokines in pDCs through TSPO. Furthermore, viability of pDCs was significantly promoted by vinpocetine. These findings imply that vinpocetine serves as an immunomodulatory agent for pDCs and may be applied for the treatment of pDCs-related autoimmune diseases.

Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector T cells via the cytokine TGF-β

PubMed Central

Yu, Chun I; Becker, Christian; Wang, Yuanyuan; Marches, Florentina; Helft, Julie; Leboeuf, Marylene; Anguiano, Esperanza; Pourpe, Stephane; Goller, Kristina; Pascual, Virginia; Banchereau, Jacques; Merad, Miriam; Palucka, Karolina

2013-01-01

Summary In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity generated to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promoted CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound cytokine TGF-β1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. PMID:23562160

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.

Isolation of Human Skin Dendritic Cell Subsets.

PubMed

Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

2016-01-01

Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (<1 % of mononuclear cells) and have a less mature phenotype than their tissue counterparts (MacDonald et al., Blood. 100:4512-4520, 2002; Haniffa et al., Immunity 37:60-73, 2012). In contrast, the skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of Legionella pneumophila

PubMed Central

Nogueira, Catarina V.; Lindsten, Tullia; Jamieson, Amanda M.; Case, Christopher L.; Shin, Sunny; Thompson, Craig B.; Roy, Craig R.

2009-01-01

Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replication of pathogens compared to macrophages, a property that could prevent DCs from enhancing pathogen dissemination. To understand DC responses to pathogens, we investigated the mechanisms by which mouse DCs are able to restrict replication of the intracellular pathogen Legionella pneumophila. We show that both DCs and macrophages have the ability to interfere with L. pneumophila replication through a cell death pathway mediated by caspase-1 and Naip5. L. pneumophila that avoided Naip5-dependent responses, however, showed robust replication in macrophages but remained unable to replicate in DCs. Apoptotic cell death mediated by caspase-3 was found to occur much earlier in DCs following infection by L. pneumophila compared to macrophages infected similarly. Eliminating the pro-apoptotic proteins Bax and Bak or overproducing the anti-apoptotic protein Bcl-2 were both found to restore L. pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication. PMID:19521510

Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy.

PubMed

Nguyen-Pham, Thanh-Nhan; Yang, Deok-Hwan; Nguyen, Truc-Anh Thi; Lim, Mi-Seon; Hong, Cheol Yi; Kim, Mi-Hyun; Lee, Hyun Ju; Lee, Youn-Kyung; Cho, Duck; Bae, Soo-Young; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Chung, Ik-Joo; Kim, Hyeoung-Joon; Lee, Je-Jung

2012-01-01

Dendritic cell (DC)-based vaccines continue to be considered an attractive tool for cancer immunotherapy. DCs require an additional signal from the environment or other immune cells to polarize the development of immune responses toward T helper 1 (Th1) or Th2 responses. DCs play a role in natural killer (NK) cell activation, and NK cells are also able to activate and induce the maturation of DCs. We investigated the types of NK cells that can induce the maturation and enhanced function of DCs and the conditions under which these interactions occur. DCs that were activated by resting NK cells in the presence of inflammatory cytokines exhibited increased expression of several costimulatory molecules and an enhanced ability to produce IL-12p70. NK cell-stimulated DCs potently induced Th1 polarization and exhibited the ability to generate tumor antigen-specific cytotoxic T lymphocyte responses. Our data demonstrate that functional DCs can be generated by coculturing immature DCs with freshly isolated resting NK cells in the presence of Toll-like receptor agonists and proinflammatory cytokines and that the resulting DCs effectively present antigens to induce tumor-specific T-cell responses, which suggests that these cells may be useful for cancer immunotherapy.

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.

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.

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.

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.

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

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/.

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

PubMed

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

2018-05-04

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

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

PubMed

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

2015-02-19

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

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

PubMed Central

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

2012-01-01

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

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.

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

PubMed

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

2013-03-14

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

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

PubMed Central

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

2012-01-01

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

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.

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

PubMed

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

2015-01-01

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

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

PubMed

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

2017-08-01

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

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

PubMed

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

2017-09-01

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

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.

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

Cumulative effects of anodal and priming cathodal tDCS on pegboard test performance and motor cortical excitability.

PubMed

Christova, Monica; Rafolt, Dietmar; Gallasch, Eugen

2015-01-01

Transcranial direct current stimulation (tDCS) protocols applied over the primary motor cortex are associated with changes in motor performance. This transcranial magnetic stimulation (TMS) study examines whether cathodal tDCS prior to motor training, combined with anodal tDCS during motor training improves motor performance and off-line learning. Three study groups (n=36) were trained on the grooved pegboard test (GPT) in a randomized, between-subjects design: SHAM-sham stimulation prior and during training, STIM1-sham stimulation prior and atDCS during training, STIM2-ctDCS stimulation prior and atDCS during training. Motor performance was assessed by GPT completion time and retested 14 days later to determine off-line learning. Cortical excitability was assessed via TMS at baseline (T0), prior training (T1), after training (T2), and 60 min after training (T3). Motor evoked potentials (MEP) were recorded from m. abductor pollicis brevis of the active left hand. GPT completion time was reduced for both stimulated groups compared to SHAM. For STIM2 this reduction in time was significantly higher than for STIM1 and further off-line learning occurred after STIM2. After ctDCS at T1, MEP amplitude and intracortical facilitation was decreased and intracortical inhibition was increased. After atDCS at T2, an opposite effect was observed for STIM1 and STIM2. For STIM2 these neuromodulatory effects were retained until T3. It is concluded that application of atDCS during the training improves pegboard performance and that additional priming with ctDCS has a positive effect on off-line learning. These cumulative behavioral gains were indicated by the preceding neuromodulatory changes. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2018-03-01

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

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

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

PubMed Central

Roy, Abhrajeet; Baxter, Bryan

2014-01-01

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

Acute seizure suppression by transcranial direct current stimulation in rats

PubMed Central

Dhamne, Sameer C; Ekstein, Dana; Zhuo, Zhihong; Gersner, Roman; Zurakowski, David; Loddenkemper, Tobias; Pascual-Leone, Alvaro; Jensen, Frances E; Rotenberg, Alexander

2015-01-01

Objective Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition. Methods Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS. Results Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection. Interpretation These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition. PMID:26339678

Decompression sickness during simulated extravehicular activity: ambulation vs. non-ambulation.

PubMed

Webb, James T; Beckstrand, Devin P; Pilmanis, Andrew A; Balldin, Ulf I

2005-08-01

Extravehicular activity (EVA) is required from the International Space Station on a regular basis. Because of the weightless environment during EVA, physical activity is performed using mostly upper-body movements since the lower body is anchored for stability. The adynamic model (restricted lower-body activity; non-ambulation) was designed to simulate this environment during earthbound studies of decompression sickness (DCS) risk. DCS symptoms during ambulatory (walking) and non-ambulatory high altitude exposure activity were compared. The objective was to determine if symptom incidences during ambulatory and non-ambulatory exposures are comparable and provide analogous estimates of risk under otherwise identical conditions. A retrospective analysis was accomplished on DCS symptoms from 2010 ambulatory and 330 non-ambulatory exposures. There was no significant difference between the overall incidence of DCS or joint-pain DCS in the ambulatory (49% and 40%) vs. the non-ambulatory exposures (53% and 36%; p > 0.1). DCS involving joint pain only in the lower body was higher during ambulatory exposures (28%) than non-ambulatory exposures (18%; p < 0.01). Non-ambulatory exposures terminated more frequently with non-joint-pain DCS (17%) or upper-body-only joint pain (18%) as compared with ambulatory exposures, 9% and 11% (p < 0.01), respectively. These findings show that lower-body, weight-bearing activity shifts the incidence of joint-pain DCS from the upper body to the lower body without altering the total incidence of DCS or joint-pain DCS. Use of data from previous and future subject exposures involving ambulatory activity while decompressed appears to be a valid analogue of non-ambulatory activity in determining DCS risk during simulated EVA studies.

Characterization of Escherichia coli d-Cycloserine Transport and Resistant Mutants

PubMed Central

Baisa, Gary; Stabo, Nicholas J.

2013-01-01

d-Cycloserine (DCS) is a broad-spectrum antibiotic that inhibits d-alanine ligase and alanine racemase activity. When Escherichia coli K-12 or CFT073 is grown in minimal glucose or glycerol medium, CycA transports DCS into the cell. E. coli K-12 cycA and CFT073 cycA mutant strains display increased DCS resistance when grown in minimal medium. However, the cycA mutants exhibit no change in DCS sensitivity compared to their parental strains when grown in LB (CFT073 and K-12) or human urine (CFT073 only). These data suggest that cycA does not participate in DCS sensitivity when strains are grown in a non-minimal medium. The small RNA GvcB acts as a negative regulator of E. coli K-12 cycA expression when grown in LB. Three E. coli K-12 gcvB mutant strains failed to demonstrate a change in DCS sensitivity when grown in LB. This further suggests a limited role for cycA in DCS sensitivity. To aid in the identification of E. coli genes involved in DCS sensitivity when grown on complex media, the Keio K-12 mutant collection was screened for DCS-resistant strains. dadA, pnp, ubiE, ubiF, ubiG, ubiH, and ubiX mutant strains showed elevated DCS resistance. The phenotypes associated with these mutants were used to further define three previously characterized E. coli DCS-resistant strains (χ316, χ444, and χ453) isolated by Curtiss and colleagues (R. Curtiss, III, L. J. Charamella, C. M. Berg, and P. E. Harris, J. Bacteriol. 90:1238–1250, 1965). A dadA mutation was identified in both χ444 and χ453. In addition, results are presented that indicate for the first time that DCS can antagonize d-amino acid dehydrogenase (DadA) activity. PMID:23316042

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.

The Double-Stranded RNA Bluetongue Virus Induces Type I Interferon in Plasmacytoid Dendritic Cells via a MYD88-Dependent TLR7/8-Independent Signaling Pathway

PubMed Central

Ruscanu, Suzana; Pascale, Florentina; Bourge, Mickael; Hemati, Behzad; Elhmouzi-Younes, Jamila; Urien, Céline; Bonneau, Michel; Takamatsu, Haru; Hope, Jayne; Mertens, Peter; Meyer, Gilles; Stewart, Meredith; Roy, Polly; Meurs, Eliane F.; Dabo, Stéphanie; Zientara, Stéphan; Breard, Emmanuel; Sailleau, Corinne; Chauveau, Emilie; Vitour, Damien; Charley, Bernard

2012-01-01

Dendritic cells (DCs), especially plasmacytoid DCs (pDCs), produce large amounts of alpha/beta interferon (IFN-α/β) upon infection with DNA or RNA viruses, which has impacts on the physiopathology of the viral infections and on the quality of the adaptive immunity. However, little is known about the IFN-α/β production by DCs during infections by double-stranded RNA (dsRNA) viruses. We present here novel information about the production of IFN-α/β induced by bluetongue virus (BTV), a vector-borne dsRNA Orbivirus of ruminants, in sheep primary DCs. We found that BTV induced IFN-α/β in skin lymph and in blood in vivo. Although BTV replicated in a substantial fraction of the conventional DCs (cDCs) and pDCs in vitro, only pDCs responded to BTV by producing a significant amount of IFN-α/β. BTV replication in pDCs was not mandatory for IFN-α/β production since it was still induced by UV-inactivated BTV (UV-BTV). Other inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-12p40, were also induced by UV-BTV in primary pDCs. The induction of IFN-α/β required endo-/lysosomal acidification and maturation. However, despite being an RNA virus, UV-BTV did not signal through Toll-like receptor 7 (TLR7) for IFN-α/β induction. In contrast, pathways involving the MyD88 adaptor and kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) were implicated. This work highlights the importance of pDCs for the production of innate immunity cytokines induced by a dsRNA virus, and it shows that a dsRNA virus can induce IFN-α/β in pDCs via a novel TLR-independent and Myd88-dependent pathway. These findings have implications for the design of efficient vaccines against dsRNA viruses. PMID:22438548

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

PubMed Central

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

2005-01-01

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

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model

PubMed Central

Hamano, Y; Abe, M; Matsuoka, S; Zhang, D; Kondo, Y; Kagami, Y; Ishigami, A; Maruyama, N; Tsuruta, Y; Yumura, W; Suzuki, K

2014-01-01

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80+ cells, CD3+CD4−CD8− T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80low cells were observed in crescent, while F4/80high cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80+ cells in crescents correlated significantly with F4/80+ cell numbers in PB, but not with numbers of F4/80+ cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80+ cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80+ cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis. PMID:24654803

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

PubMed Central

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

2006-01-01

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

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

PubMed

Krause, Vanessa; Weber, Juliane; Pollok, Bettina

2014-01-01

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

The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells

PubMed Central

Crozat, Karine; Guiton, Rachel; Contreras, Vanessa; Feuillet, Vincent; Dutertre, Charles-Antoine; Ventre, Erwan; Vu Manh, Thien-Phong; Baranek, Thomas; Storset, Anne K.; Marvel, Jacqueline; Boudinot, Pierre; Hosmalin, Anne; Schwartz-Cornil, Isabelle

2010-01-01

Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria. PMID:20479118

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

PubMed Central

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

2015-01-01

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

Age-dependent effects of brain stimulation on network centrality.

PubMed

Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus; Prehn, Kristin; Thielscher, Axel; Ittermann, Bernd; Flöel, Agnes

2018-04-18

Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation originated from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-07-01

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

Behavioural and neurofunctional impact of transcranial direct current stimulation on somatosensory learning.

PubMed

Hilgenstock, Raphael; Weiss, Thomas; Huonker, Ralph; Witte, Otto W

2016-04-01

We investigated the effect of repeated delivery of anodal transcranial direct current stimulation (tDCS) on somatosensory performance and long-term learning. Over the course of five days, tDCS was applied to the primary somatosensory cortex (S1) by means of neuronavigation employing magnetencephalography (MEG). Compared to its sham application, tDCS promoted tactile learning by reducing the two-point discrimination threshold assessed by the grating orientation task (GOT) primarily by affecting intersessional changes in performance. These results were accompanied by alterations in the neurofunctional organization of the brain, as revealed by functional magnetic resonance imaging conducted prior to the study, at the fifth day of tDCS delivery and four weeks after the last application of tDCS. A decrease in activation at the primary site of anodal tDCS delivery in the left S1 along retention of superior tactile acuity was observed at follow-up four weeks after the application of tDCS. Thus, we demonstrate long-term effects that repeated tDCS imposes on somatosensory functioning. This is the first study to provide insight into the mode of operation of tDCS on the brain's response to long-term perceptual learning, adding an important piece of evidence from the domain of non-invasive brain stimulation to show that functional changes detectable by fMRI in primary sensory cortices participate in perceptual learning. © 2016 Wiley Periodicals, Inc.

Uterine DCs are crucial for decidua formation during embryo implantation in mice

PubMed Central

Plaks, Vicki; Birnberg, Tal; Berkutzki, Tamara; Sela, Shay; BenYashar, Adi; Kalchenko, Vyacheslav; Mor, Gil; Keshet, Eli; Dekel, Nava; Neeman, Michal; Jung, Steffen

2008-01-01

Implantation is a key stage during pregnancy, as the fate of the embryo is often decided upon its first contact with the maternal endometrium. Around this time, DCs accumulate in the uterus; however, their role in pregnancy and, more specifically, implantation, remains unknown. We investigated the function of uterine DCs (uDCs) during implantation using a transgenic mouse model that allows conditional ablation of uDCs in a spatially and temporally regulated manner. Depletion of uDCs resulted in a severe impairment of the implantation process, leading to embryo resorption. Depletion of uDCs also caused embryo resorption in syngeneic and T cell–deficient pregnancies, which argues against a failure to establish immunological tolerance during implantation. Moreover, even in the absence of embryos, experimentally induced deciduae failed to adequately form. Implantation failure was associated with impaired decidual proliferation and differentiation. Dynamic contrast-enhanced MRI revealed perturbed angiogenesis characterized by reduced vascular expansion and attenuated maturation. We suggest therefore that uDCs directly fine-tune decidual angiogenesis by providing two critical factors, sFlt1 and TGF-β1, that promote coordinated blood vessel maturation. Collectively, uDCs appear to govern uterine receptivity, independent of their predicted role in immunological tolerance, by regulating tissue remodeling and angiogenesis. Importantly, our results may aid in understanding the limited implantation success of embryos transferred following in vitro fertilization. PMID:19033665

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

PubMed

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

PubMed Central

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity. PMID:29320502

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 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 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.

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

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

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren's Syndrome.

PubMed

Iizuka-Koga, Mana; Asashima, Hiromitsu; Ando, Miki; Lai, Chen-Yi; Mochizuki, Shinji; Nakanishi, Mahito; Nishimura, Toshinobu; Tsuboi, Hiroto; Hirota, Tomoya; Takahashi, Hiroyuki; Matsumoto, Isao; Otsu, Makoto; Sumida, Takayuki

2017-05-09

Although it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren's syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs). T-iPS-DCs had dendritic cell-like morphology, and expressed CD11c, HLA-DR, CD80, CD86, and also BDCA-3. Compared with monocyte-derived DCs, the capacity for antigen processing was similar, and T-iPS-DCs induced the proliferative response of autoreactive CD4+ T cells. Moreover, we could evaluate T cell functions of the patient with SS. In conclusion, we obtained adequate numbers of DCs from T-iPSCs, which could be used to characterize pathogenic T cells in autoimmune diseases such as SS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Bantam System Technology Project

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

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

CD22 expression on blastic plasmacytoid dendritic cell neoplasms and reactivity of anti-CD22 antibodies to peripheral blood dendritic cells.

PubMed

Reineks, Edmunds Z; Osei, Ebenezer S; Rosenberg, Arlene; Auletta, Jeffrey; Meyerson, Howard J

2009-07-01

We identified CD22 expression on a blastic plasmacytoid dendritic cell (pDC) neoplasm presenting as a leukemia in a child. CD22 expression, as determined by the antibody s-HCL-1, was also noted on the neoplastic cells from three additional patients with blastic pDC tumors identified at our institution. Subsequently we determined that peripheral blood pDCs react with the s-HCL-1 antibody demonstrating that normal pDCs express CD22. Evaluation of five additional anti-CD22 antibodies indicated that staining of pDCs with these reagents was poor except for s-HCL-1. Therefore, the detection of CD22 on pDCs is best demonstrated with the use of this specific antibody clone. All anti-CD22 antibodies stained conventional DCs. We also evaluated the reactivity of the anti-CD22 antibodies with basophils and noted that the pattern of staining was similar to that seen with pDCs. The studies demonstrate that normal DCs and pDC neoplasms express CD22, and highlight clone specific differences in anti-CD22 antibody reactivity patterns on pDCs and basophils. (c) 2009 Clinical Cytometry Society.

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

PubMed Central

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

2017-01-01

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

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

PubMed Central

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

2013-01-01

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

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.

Disease-Associated Plasmacytoid Dendritic Cells

PubMed Central

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

2017-01-01

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

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

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Improved degree of conversion of model self-etching adhesives through their interaction with dentin

PubMed Central

Zhang, Ying; Wang, Yong

2011-01-01

Objective To investigate the correlation of the chemical interaction between model self-etching adhesives and dentin with the degree of conversion (DC) of the adhesives. Methods The model self-etching adhesives contained bis[2-methacryloyloxy)ethyl] phosphate (2MP) and 2-hydroxyethyl methacrylate (HEMA) with a mass ratio of 1/1, and 0-40% water contents, respectively. The adhesives were applied either onto the prepared dentin surface or unreactive substrates (such as glass slides), agitated for 15s, then light-cured for 40s. The DCs of the adhesives were determined using micro-Raman spectral and mapping analysis. Results The DCs of the adhesives cured on the dentin substrate were found to be significantly higher than those on the unreactive glass substrate. Moreover, the DCs of the adhesives displayed a decreasing trend as the distance from the dentin surface became greater. The chemical interaction of the acidic 2MP/HEMA adhesives with the mineral apatite in dentin was proposed to play a significant role for the observations. The chemical interaction could be validated by the spectral comparison in the phosphate regions of 1100 cm−1 and 960 cm−1 in the Raman spectra. The results also revealed a notable influence of water content on the DC of adhesives. The DCs of the adhesive at 10% water content exhibited the highest DC level for both substrates. Conclusions Interaction with dentin dramatically improved the degree of conversion of self-etching adhesives. Our ability to chemically characterize the a/d interface including in situ detection of the DC distribution is very important in understanding self-etching adhesive bonding under in vivo conditions. PMID:22024375

Long interspersed nuclear element-1 retroelements are expressed in patients with systemic autoimmune disease and induce type I interferon

PubMed Central

Mavragani, Clio P.; Sagalovskiy, Irina; Guo, Qiu; Nezos, Adrianos; Kapsogeorgou, Efstathia K.; Lu, Pin; Zhou, Jun Liang; Kirou, Kyriakos A.; Seshan, Surya V.; Moutsopoulos, Haralampos M.; Crow, Mary K.

2016-01-01

Objective Increased type I interferon (IFN-I) and a broad signature of IFN-I-induced gene transcripts are observed in patients with SLE and other systemic autoimmune diseases. To identify disease-relevant triggers of the IFN-I pathway we investigated whether endogenous virus-like genomic repeat elements, normally silent, might be expressed in patients with systemic autoimmune disease, activate an innate immune response and induce IFN-I. Methods Expression of IFN-I and long interspersed nuclear element-1 (LINE-1; L1) was studied in kidney tissue from lupus patients and minor salivary gland (MSG) tissue from patients with primary Sjogren’s syndrome (SS) by PCR, western blot and immunohistochemistry. Induction of IFN-I by L1 was investigated by transfection of plasmacytoid dendritic cells (pDCs) or monocytes with an L1-encoding plasmid or L1 RNA. Involvement of innate immune pathways and altered L1 methylation were assessed. Results L1 mRNA transcripts were increased in lupus nephritis kidneys and in MSG from SS patients and correlated with IFN-I expression and L1 DNA demethylation. L1 open reading frame 1/p40 protein and IFNβ were expressed in MSG ductal epithelial cells and in lupus kidneys, and IFNα was detected in infiltrating pDCs. Transfection of pDCs or monocytes with L1-encoding DNA or RNA induced IFN-I. Inhibition of TLR7/8 reduced L1 induction of IFNα in pDCs and an inhibitor of IKKε/TBK1 abrogated induction of IFN-I by L1 RNA in monocytes. Conclusion L1 genomic repeat elements represent endogenous nucleic acid triggers of the IFN-I pathway in SLE and SS and may contribute to initiation or amplification of autoimmune disease. PMID:27338297

Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer.

PubMed

Rojas-Sepúlveda, Daniel; Tittarelli, Andrés; Gleisner, María Alejandra; Ávalos, Ignacio; Pereda, Cristián; Gallegos, Iván; González, Fermín Eduardo; López, Mercedes Natalia; Butte, Jean Michel; Roa, Juan Carlos; Fluxá, Paula; Salazar-Onfray, Flavio

2018-03-29

Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4 + and CD8 + T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8 + T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches.

Manipulating the antigen-specific immune response by the hydrophobicity of amphiphilic poly(γ-glutamic acid) nanoparticles.

PubMed

Shima, Fumiaki; Akagi, Takami; Uto, Tomofumi; Akashi, Mitsuru

2013-12-01

The new generation vaccines are safe but poorly immunogenic, and thus they require the use of adjuvants. However, conventional vaccine adjuvants fail to induce potent cellular immunity, and their toxicity and side-effects hinder the clinical use. Therefore, a vaccine adjuvant which is safe and can induce an antigen-specific cellular immunity-biased immune response is urgently required. In the development of nanoparticle-based vaccine adjuvants, the hydrophobicity is one of the most important factors. It could control the interaction between the encapsulated antigens and/or nanoparticles with immune cells. In this study, nanoparticles (NPs) composed of amphiphilic poly(γ-glutamic acid)-graft-L-phenylalanine ethyl ester (γ-PGA-Phe) with various grafting degrees of hydrophobic side chains were prepared to evaluate the effect of hydrophobicity of vaccine carriers on the antigen encapsulation behavior, cellular uptake, activation of dendritic cells (DCs), and induction of antigen-specific cellular immunity-biased immune responses. These NPs could efficiently encapsulate antigens, and the uptake amount of the encapsulated antigen by DCs was dependent on the hydrophobicity of γ-PGA-Phe NPs. Moreover, the activation potential of the DCs and the induction of antigen-specific cellular immunity were correlated with the hydrophobicity of γ-PGA-Phe NPs. By controlling the hydrophobicity of antigen-encapsulated γ-PGA-Phe NPs, the activation potential of DCs was able to manipulate about 5 to 30-hold than the conventional vaccine, and the cellular immunity was about 10 to 40-hold. These results suggest that the hydrophobicity of NPs is a key factor for changing the interaction between NPs and immune cells, and thus the induction of cellular immunity-biased immune response could be achieved by controlling the hydrophobicity of them. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improved degree of conversion of model self-etching adhesives through their interaction with dentine.

PubMed

Zhang, Ying; Wang, Yong

2012-01-01

To investigate the correlation of the chemical interaction between model self-etching adhesives and dentine with the degree of conversion (DC) of the adhesives. The model self-etching adhesives contained bis[2-methacryloyloxy)ethyl] phosphate (2MP) and 2-hydroxyethyl methacrylate (HEMA) with a mass ratio of 1/1, and 0-40% water contents, respectively. The adhesives were applied either onto the prepared dentine surface or unreactive substrates (such as glass slides), agitated for 15s, then light-cured for 40s. The DCs of the adhesives were determined using micro-Raman spectral and mapping analysis. The DCs of the adhesives cured on the dentine substrate were found to be significantly higher than those on the unreactive glass substrate. Moreover, the DCs of the adhesives displayed a decreasing trend as the distance from the dentine surface became greater. The chemical interaction of the acidic 2MP/HEMA adhesives with the mineral apatite in dentine was proposed to play a significant role for the observations. The chemical interaction could be validated by the spectral comparison in the phosphate regions of 1100 cm(-1) and 960 cm(-1) in the Raman spectra. The results also revealed a notable influence of water content on the DC of adhesives. The DCs of the adhesive at 10% water content exhibited the highest DC level for both substrates. Interaction with dentine dramatically improved the degree of conversion of self-etching adhesives. Our ability to chemically characterise the a/d interface including in situ detection of the DC distribution is very important in understanding self-etching adhesive bonding under in vivo conditions. Copyright © 2011 Elsevier Ltd. All rights reserved.

The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses.

PubMed

Durán-Aniotz, Claudia; Segal, Gabriela; Salazar, Lorena; Pereda, Cristián; Falcón, Cristián; Tempio, Fabián; Aguilera, Raquel; González, Rodrigo; Pérez, Claudio; Tittarelli, Andrés; Catalán, Diego; Nervi, Bruno; Larrondo, Milton; Salazar-Onfray, Flavio; López, Mercedes N

2013-04-01

Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH(+) with respect to DTH(-) unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood. Healthy donors and melanoma patient's lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release. Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4(+) TGF-β(+)) regulatory T lymphocytes compared with healthy donors. Notably, DTH(+) patients showed a threefold reduction of Th3 cells compared with DTH(-) patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-γ releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH(+) with respect to DTH(-) patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response. Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients.

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study.

PubMed

Abend, Rany; Sar-El, Roy; Gonen, Tal; Jalon, Itamar; Vaisvaser, Sharon; Bar-Haim, Yair; Hendler, Talma

2018-05-09

Implicit regulation of emotions involves medial-prefrontal cortex (mPFC) regions exerting regulatory control over limbic structures. Diminished regulation relates to aberrant mPFC functionality and psychopathology. Establishing means of modulating mPFC functionality could benefit research on emotion and its dysregulation. Here, we tested the capacity of transcranial direct current stimulation (tDCS) targeting mPFC to modulate subjective emotional states by facilitating implicit emotion regulation. Stimulation was applied concurrently with functional magnetic resonance imaging to validate its neurobehavioral effect. Sixteen participants were each scanned twice, counterbalancing active and sham tDCS application, while undergoing negative mood induction (clips featuring negative vs. neutral contents). Effects of stimulation on emotional experience were assessed using subjective and neural measures. Subjectively, active stimulation led to significant reduction in reported intensity of experienced emotions to negatively valenced (p = 0.005) clips but not to neutral clips (p > 0.99). Active stimulation further mitigated a rise in stress levels from pre- to post-induction (sham: p = 0.004; active: p = 0.15). Neurally, stimulation increased activation in mPFC regions associated with implicit emotion regulation (ventromedial-prefrontal cortex; subgenual anterior-cingulate cortex, sgACC), and in ventral striatum, a core limbic structure (all ps < 0.05). Stimulation also altered functional connectivity (assessed using whole-brain psycho-physiological interaction) between these regions, and with additional limbic regions. Stimulation-induced sgACC activation correlated with reported emotion intensity and depressive symptoms (rs > 0.64, ps < 0.018), suggesting individual differences in stimulation responsivity. Results of this study indicate the potential capacity of tDCS to facilitate brain activation in mPFC regions underlying implicit regulation of emotion and accordingly modulate subjective emotional experiences. © 2018 International Neuromodulation Society.

Transcranial direct current stimulation (tDCS) and language

PubMed Central

Monti, Alessia; Ferrucci, Roberta; Fumagalli, Manuela; Mameli, Francesca; Cogiamanian, Filippo; Ardolino, Gianluca; Priori, Alberto

2013-01-01

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia. PMID:23138766

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

NASA Technical Reports Server (NTRS)

Demboski, John T.; Pilmanis, Andrew A.

1994-01-01

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

Coincident Occurrences of Tropical Individual Cirrus Clouds and Deep Convective Systems Derived from TRMM Observations

NASA Technical Reports Server (NTRS)

Lin, Bing; Xu, Kuan-Man; Minnis, Patrick; Wielicki, Bruce A.; Hu, Yongxiang; Chambers, Lin; Fan, Alice; Sun, Wenbo

2007-01-01

Measurements of cloud properties and atmospheric radiation taken between January and August 1998 by the Tropical Rainfall Measuring Mission (TRMM) satellite were used to investigate the effect of spatial and temporal scales on the coincident occurrences of tropical individual cirrus clouds (ICCs) and deep convective systems (DCSs). It is found that there is little or even negative correlation between instantaneous occurrences of ICC and DCS in small areas, in which both types of clouds cannot grow and expand simultaneously. When spatial and temporal domains are increased, ICCs become more dependent on DCSs due to the origination of many ICCs from DCSs and moisture supply from the DCS in the upper troposphere for the ICCs to grow, resulting in significant positive correlation between the two types of tropical high clouds in large spatial and long temporal scales. This result may suggest that the decrease of tropical high clouds with SST from model simulations is likely caused by restricted spatial domains and limited temporal periods. Finally, the radiative feedback due to the change in tropical high cloud area coverage with sea surface temperature appears small and about -0.14 W/sq m per degree Kelvin.

Public Perceptions of Doctors of Chiropractic: Results of a National Survey and Examination of Variation According to Respondents' Likelihood to Use Chiropractic, Experience With Chiropractic, and Chiropractic Supply in Local Health Care Markets.

PubMed

Weeks, William B; Goertz, Christine M; Meeker, William C; Marchiori, Dennis M

2015-10-01

The purpose of this study was to determine whether general perceptions of doctors of chiropractic (DCs) varied according to likeliness to use chiropractic care, whether particular demographic characteristics were associated with chiropractic care use, and whether perception of DCs varied according to the per-capita supply of DCs in local health care markets. We performed a secondary analysis of results from a 26-item nationally representative survey of 5422 members of The Gallup Panel that was conducted in the spring of 2015 (response rate, 29%) that sought to elicit the perceptions and use of DCs by US adults. We compared survey responses across: (1) respondents who had different likelihoods to use DCs for treatment of neck or back pain and (2) respondents who had different experiences using DCs. We linked respondents' zip codes to hospital referral regions for which we had the per-capita supply of DCs. Using the χ(2) test, we examined relationships between likeliness to use a DC, experience using a DC, respondent demographic variables, perceptions of DCs, and the per-capita supply of DCs in the local health care market. Most (61.4%) respondents believed that chiropractic care was effective at treating neck and back pain, 52.6% thought DCs were trustworthy, and 24.2% thought chiropractic care was dangerous; however, as respondents' likelihood to use a DC increased, perceptions of effectiveness and trustworthiness increased, and perceptions of danger decreased. Of all 5422 survey respondents, 744 or 13.7% indicated that they had seen a DC within the last 12 months. As one moved from distant to more recent experience using a DC, respondents were more likely to be female, married, white, and employed; those who had a distant history of using a DC were older and more likely to be retired than the other groups. A higher per-capita supply of DCs was associated with higher utilization rates and showed a more favorable regard for DCs. US adults often use chiropractic care, generally regard DCs favorably, and largely perceive that chiropractic care is safe. Where there is a higher per-capita supply of DCs in the local health care market, utilization and positive perceptions of chiropractic are higher. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

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.

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

PubMed

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

2017-01-01

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Inorganic arsenic impairs differentiation and functions of human dendritic cells

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

Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier

2013-01-15

Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis.more » Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by inducing necrosis ► Arsenite (0.1 to 0.5 μM) slightly reduces endocytotic activity of immature DCs ► Arsenite (0.1 to 0.5 μM) represses expression of IL-12p70 and IL-23 in activated DCs ► Arsenite (0.1 to 0.5 μM) reduces the ability of DCs to activate human T lymphocytes.« less

Sphingosine 1-Phosphate- and C-C Chemokine Receptor 2-Dependent Activation of CD4+ Plasmacytoid Dendritic Cells in the Bone Marrow Contributes to Signs of Sepsis-Induced Immunosuppression

PubMed Central

Smirnov, Anna; Pohlmann, Stephanie; Nehring, Melanie; Ali, Shafaqat; Mann-Nüttel, Ritu; Scheu, Stefanie; Antoni, Anne-Charlotte; Hansen, Wiebke; Büettner, Manuela; Gardiasch, Miriam J.; Westendorf, Astrid M.; Wirsdörfer, Florian; Pastille, Eva; Dudda, Marcel; Flohé, Stefanie B.

2017-01-01

Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis. Bone marrow cells (BMC) were isolated after sham or CLP operation, the cellular composition was analyzed, and bone marrow-derived DCs (BMDCs) were generated in vitro. From 24 h on after CLP, BMC gave rise to BMDC that released enhanced levels of IL-10. In parallel, a population of CD11chiMHCII+CD4+ DCs expanded in the bone marrow in a MyD88-dependent manner. Prior depletion of the CD11chiMHCII+CD4+ DCs from BMC in vitro reversed the increased IL-10 secretion of subsequently differentiating BMDC. The expansion of the CD11chiMHCII+CD4+ DC population in the bone marrow after CLP required the function of sphingosine 1-phosphate receptors and C-C chemokine receptor (CCR) 2, the receptor for C-C chemokine ligand (CCL) 2, but was not associated with monocyte mobilization. CD11chiMHCII+CD4+ DCs were identified as plasmacytoid DCs (pDCs) that had acquired an activated phenotype according to their increased expression of MHC class II and CD86. A redistribution of CD4+ pDCs from MHC class II− to MHC class II+ cells concomitant with enhanced expression of CD11c finally led to the rise in the number of CD11chiMHCII+CD4+ DCs. Enhanced levels of CCL2 were found in the bone marrow of septic mice and the inhibition of CCR2 dampened the expression of CD86 on CD4+ pDCs after CLP in vitro. Depletion of pDCs reversed the bias of splenic DCs toward increased IL-10 synthesis after CLP in vivo. Thus, during polymicrobial sepsis, CD4+ pDCs are activated in the bone marrow and induce functional reprogramming of differentiating BMDC toward an immunosuppressive phenotype. PMID:29218051

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

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.

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.

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.

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

PubMed

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

2016-01-01

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

In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

PubMed Central

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

2015-01-01

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection. PMID:25658925

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

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

PubMed

Oldrati, Viola; Colombo, Barbara; Antonietti, Alessandro

2018-01-01

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

Immunostimulatory activities of dendritic cells loaded with adenovirus vector carrying HBcAg/HBsAg

PubMed Central

Jia, Hongyu; Li, Chunling; Zhang, Yimin; Yu, Liang; Xiang, Dairong; Liu, Jun; Chen, Fengzhe; Han, Xiaochun

2015-01-01

Objective: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). Methods: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte reaction (MLR) was used to evaluate the T-cell stimulatory capacity, and HBcAg-specific cytotoxic T lymphocyte (CTL) activity was assessed. Results: Phenotypic analysis showed that DCs transfected with rAd or pulsed with HBcAg antigen exhibited mature phenotypes. MLR indicated no significant differences in stimulating T-cell proliferation between the DC/rAd and DC/HBcAg groups. When mixed with DCs, Th and Tc cells mainly secreted IFN-γ, indicating type I immune responses. In vaccinated mice, DCs transduced with rAd and pulsed with HBcAg induced significantly more IFN-γ secretion from Th cells, compared with DNA vaccine, indicating stronger Th1 response. Moreover, DCs transduced with rAd stimulated Tc cells to produce more IFN-γ, indicating stronger Tc1 response. In vaccinated mice, HBcAg-specific CTL activities were decreased in the following order: the DC/Ad-C+Ad-S, DC/Ad-C, DC/Ad-S, DC/HBcAg, and DNA vaccine groups. Conclusion: DCs transfected with rAd induce stronger Th1/Tc1 (type I) cell immune responses and specific CTL response than HBcAg-pulsed DCs or DNA vaccine. Our findings suggest that DCs transfected with rAd-C/rAd-S might provide an effective approach in the treatment of persistent hepatitis B virus infection. PMID:26064236

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

PubMed

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

2016-03-01

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

Regulatory dendritic cells: there is more than just immune activation.

PubMed

Schmidt, Susanne V; Nino-Castro, Andrea C; Schultze, Joachim L

2012-01-01

The immune system exists in a delicate equilibrium between inflammatory responses and tolerance. This unique feature allows the immune system to recognize and respond to potential threats in a controlled but normally limited fashion thereby preventing a destructive overreaction against healthy tissues. While the adaptive immune system was the major research focus concerning activation vs. tolerance in the immune system more recent findings suggest that cells of the innate immune system are important players in the decision between effective immunity and induction of tolerance or immune inhibition. Among immune cells of the innate immune system dendritic cells (DCs) have a special function linking innate immune functions with the induction of adaptive immunity. DCs are the primary professional antigen presenting cells (APCs) initiating adaptive immune responses. They belong to the hematopoietic system and arise from CD34(+) stem cells in the bone marrow. Particularly in the murine system two major subgroups of DCs, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) can be distinguished. DCs are important mediators of innate and adaptive immunity mostly due to their remarkable capacity to present processed antigens via major histocompatibility complexes (MHC) to T cells and B cells in secondary lymphoid organs. A large body of literature has been accumulated during the last two decades describing which role DCs play during activation of T cell responses but also during the establishment and maintenance of central tolerance (Steinman et al., 2003). While the concept of peripheral tolerance has been clearly established during the last years, the role of different sets of DCs and their particular molecular mechanisms of immune deviation has not yet fully been appreciated. In this review we summarize accumulating evidence about the role of regulatory DCs in situations where the balance between tolerance and immunogenicity has been altered leading to pathologic conditions such as chronic inflammation or malignancies.

Plasmacytoid Dendritic Cells in the Tumor Microenvironment: Immune Targets for Glioma Therapeutics12

PubMed Central

Candolfi, Marianela; King, Gwendalyn D; Yagiz, Kader; Curtin, James F; Mineharu, Yohei; Muhammad, AKM Ghulam; Foulad, David; Kroeger, Kurt M; Barnett, Nick; Josien, Regis; Lowenstein, Pedro R; Castro, Maria G

2012-01-01

Adenovirus-mediated delivery of the immune-stimulatory cytokine Flt3L and the conditionally cytotoxic thymidine kinase (TK) induces tumor regression and long-term survival in preclinical glioma (glioblastoma multiforme [GBM]) models. Flt3L induces expansion and recruitment of plasmacytoid dendritic cells (pDCs) into the brain. Although pDCs can present antigen and produce powerful inflammatory cytokines, that is, interferon α (IFN-α), their role in tumor immunology remains debated. Thus, we studied the role of pDCs and IFN-α in Ad.TK/GCV+ Ad.Flt3L-mediated anti-GBM therapeutic efficacy. Our data indicate that the combined gene therapy induced recruitment of plasmacytoid DCs (pDCs) into the tumor mass; which were capable of in vivo phagocytosis, IFN-α release, and T-cell priming. Thus, we next used either pDCs or an Ad vector encoding IFN-α delivered within the tumor microenvironment. When rats were treated with Ad.TK/GCV in combination with pDCs or Ad-IFN-α, they exhibited 35% and 50% survival, respectively. However, whereas intracranial administration of Ad.TK/GCV + Ad.Flt3L exhibited a high safety profile, Ad-IFN-α led to severe local inflammation, with neurologic and systemic adverse effects. To elucidate whether the efficacy of the immunotherapy was dependent on IFN-α-secreting pDCs, we administered an Ad vector encoding B18R, an IFN-α antagonist, which abrogated the antitumoral effect of Ad.TK/GCV + Ad.Flt3L. Our data suggest that IFN-α release by activated pDCs plays a critical role in the antitumor effect mediated by Ad.TK/GCV + Ad.Flt3L. In summary, taken together, our results demonstrate that pDCs mediate anti-GBM therapeutic efficacy through the production of IFN-α, thus manipulation of pDCs constitutes an attractive new therapeutic target for the treatment of GBM. PMID:22952428

Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4+ Vα24 natural killer T cells expressing CD40L

PubMed Central

Nieda, M; Kikuchi, A; Nicol, A; Koezuka, Y; Ando, Y; Ishihara, S; Lapteva, N; Yabe, T; Tokunaga, K; Tadokoro, K; Juji, T

2001-01-01

Human Vα24 natural killer T (Vα24NKT) cells are activated by α-glycosylceramide-pulsed dendritic cells (DCs) in a CD1d-dependent and T-cell receptor-mediated manner. There are two major subpopulations of Vα24NKT cells, CD4– CD8– Vα24NKT and CD4+ Vα24NKT cells. We have recently shown that activated CD4– CD8– Vα24NKT cells have cytotoxic activity against DCs, but knowledge of the molecules responsible for cytotoxicity of Vα24NKT cells is currently limited. We aimed to investigate whether CD4+ Vα24NKT cells also have cytotoxic activity against DCs and to determine the mechanisms underlying any observed cytotoxic activity. We demonstrated that activated CD4+ Vα24NKT cells [CD40 ligand (CD40L) -positive] have cytotoxic activity against DCs (strongly CD40-positive), but not against monocytes (weakly CD40-positive) or phytohaemagglutinin blast T cells (CD40-negative), and that apoptosis of DCs significantly contributes to the observed cytotoxicity. The apoptosis of DCs following culture with activated CD4+ Vα24NKT cells, but not with resting CD4+ Vα24NKT cells (CD40L-negative), was partially inhibited by anti-CD40L mAb. Direct ligation of CD40 on the DCs by the anti-CD40 antibody also induced apoptosis of DCs. Our results suggest that CD40–CD40L interaction plays an important role in the induction of apoptosis of DCs following culture with activated CD4+ Vα24NKT cells. The apoptosis of DCs from normal donors, triggered by the CD40–CD40L interaction, may contribute to the homeostatic regulation of the normal human immune system, preventing the interminable activation of activated CD4+ Vα24NKT cells by virtue of apoptosis of DCs. PMID:11260318

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.

Regulatory dendritic cells: there is more than just immune activation

PubMed Central

Schmidt, Susanne V.; Nino-Castro, Andrea C.; Schultze, Joachim L.

2012-01-01

The immune system exists in a delicate equilibrium between inflammatory responses and tolerance. This unique feature allows the immune system to recognize and respond to potential threats in a controlled but normally limited fashion thereby preventing a destructive overreaction against healthy tissues. While the adaptive immune system was the major research focus concerning activation vs. tolerance in the immune system more recent findings suggest that cells of the innate immune system are important players in the decision between effective immunity and induction of tolerance or immune inhibition. Among immune cells of the innate immune system dendritic cells (DCs) have a special function linking innate immune functions with the induction of adaptive immunity. DCs are the primary professional antigen presenting cells (APCs) initiating adaptive immune responses. They belong to the hematopoietic system and arise from CD34+ stem cells in the bone marrow. Particularly in the murine system two major subgroups of DCs, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) can be distinguished. DCs are important mediators of innate and adaptive immunity mostly due to their remarkable capacity to present processed antigens via major histocompatibility complexes (MHC) to T cells and B cells in secondary lymphoid organs. A large body of literature has been accumulated during the last two decades describing which role DCs play during activation of T cell responses but also during the establishment and maintenance of central tolerance (Steinman et al., 2003). While the concept of peripheral tolerance has been clearly established during the last years, the role of different sets of DCs and their particular molecular mechanisms of immune deviation has not yet fully been appreciated. In this review we summarize accumulating evidence about the role of regulatory DCs in situations where the balance between tolerance and immunogenicity has been altered leading to pathologic conditions such as chronic inflammation or malignancies. PMID:22969767

Suppression of dendritic cells' maturation and functions by daidzein, a phytoestrogen

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

Yum, Min Kyu; Jung, Mi Young; Cho, Daeho

2011-12-15

Isoflavones are ubiquitous compounds in foods and in the environment in general. Daidzein and genistein, the best known of isoflavones, are structurally similar to 17{beta}-estradiol and known to exert estrogenic effects. They also evidence a broad variety of biological properties, including antioxidant, anti-carcinogenic, anti-atherogenic and anti-osteoporotic activities. Previously, daidzein was reported to increase the phagocytic activity of peritoneal macrophages and splenocyte proliferation, and to inhibit nitric oxide (NO) production in macrophages. However, its potential impacts on immune response in dendritic cells (DCs), antigen-presenting cells that link innate and adaptive immunity, have yet to be clearly elucidated. In this study, wemore » evaluated the effects of isoflavones on the maturation and activation of DCs. Isoflavones (formononetin, daidzein, equol, biochanin A, genistein) were found to differentially affect the expression of CD86, a costimulatory molecule, on lipopolysaccharide (LPS)-stimulated DCs. In particular, daidzein significantly and dose-dependently inhibited the expression levels of maturation-associated cell surface markers including CD40, costimulatory molecules (CD80, CD86), and major histocompatibility complex class II (I-A{sup b}) molecule on LPS-stimulated DCs. Daidzein also suppressed pro-inflammatory cytokine production such as IL-12p40, IL-6 and TNF-{alpha}, whereas it didn't affect IL-10 and IL-1{beta} expression. Furthermore, daidzein enhanced endocytosis and inhibited the allo-stimulatory ability of LPS-stimulated DCs on T cells, indicating that daidzein treatment can inhibit the functional maturation of DCs. These results demonstrate that daidzein may exhibit immunosuppressive activity by inhibiting the maturation and activation of DCs. -- Highlights: Black-Right-Pointing-Pointer Daidzein inhibited expression of maturation-associated cell surface markers in DCs. Black-Right-Pointing-Pointer Daidzein suppressed expression of pro-inflammatory cytokines in LPS-stimulated DCs. Black-Right-Pointing-Pointer Daidzein enhanced endocytosis and inhibited allo-stimulatory ability of DCs. Black-Right-Pointing-Pointer Daidzein exhibited immunosuppressive activity by inhibiting the activation of DCs.« less

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

PubMed

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

2017-09-01

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

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.

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

PubMed

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

2015-01-01

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

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.

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.

D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning

PubMed Central

Nic Dhonnchadha, Bríd Á; Szalay, Jonathan J; Achat-Mendes, Cindy; Platt, Donna M; Otto, Michael W; Spealman, Roger D; Kantak, Kathleen M

2010-01-01

Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared with vehicle, pretreatment with 30 mg/kg DCS 0.5 h before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species, pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared with either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 h after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse. PMID:19741593

Association of A Dilated Coronary Sinus in the Fetus with Actual and Apparent Coarctation of the Aorta and Diminutive Left Heart Structures.

PubMed

Ramaswamy, Prema; Rafii, Daniela; Osmolovsky, Marina; Agarwal, Arpit; Amirtharaj, Cynthia

2016-12-01

Evidence suggests an association between left heart obstructive lesions and dilated coronary sinus (DCS), but this has not been studied in fetuses. A retrospective review of fetal echocardiograms (FE) over an 8-year period was conducted, and patients with DCS were identified and confirmed postnatally. There were 5840 FE performed on 4920 women during this period. Of 49 patients with DCS, 22 had normal intracardiac anatomy and 27 patients had congenital heart disease (CHD) yielding an incidence of 4.6 % in the presence of CHD (27/584). Of 27 patients with DCS and CHD, approximately a third had either hypoplastic left ventricles and/or coarctations (10/27, 37 %). The incidence of left heart obstructive lesions was much higher in the presence of a DCS (37 % vs 45/557, 8 %, p < 0.0001). The odds ratio of left heart hypoplasia in fetuses with CHD and a DCS was 6.6 (95 % CI 2.8-15.3). Comparison of patients with postnatally confirmed coarctation with those with normal intracardiac anatomy with DCS, revealed that in the former, the right ventricle (p = 0.005), pulmonic valve annulus (p = 0.0001) and the tricuspid inflow were larger (p = 0.001) compared to corresponding left-sided structures. The size of the DCS was not significantly different between the two groups, but in the former, the DCS was more closely related to the posterior leaflet of the mitral valve and caused a significant diminution of the mitral inflow. Our study suggests a strong association, possibly causal, between left heart obstructive lesions and DCS in utero.