Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS)

Viewing images of other humans in pain elicits a variety of responses including distress, anxiety, and a sensation that is similar to pain. We aimed to evaluate whether transcranial direct current stimulation (tDCS) could be effective in modulating the emotional aspects of pain as to further explore mechanisms of tDCS in pain relief. Twenty-three healthy subjects rated images with respect to unpleasantness and discomfort/pain (baseline), and then received stimulation with tDCS under four different conditions of stimulation: anodal tDCS of the left primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1); and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. During each stimulation session (after 3 min of stimulation), subjects were shown a new set of aversive images and were again asked to rate the images with respect to unpleasantness and discomfort/pain. The results showed that ratings of unpleasantness and discomfort/pain were significantly decreased during DLPFC tDCS only, as compared to baseline and sham tDCS. The other conditions of stimulation (M1 and V1 tDCS) did not result in any significant changes. These results support the notion that DLPFC is a critical area for the emotional processing of pain and also suggests that DLPFC may be a potential target of stimulation for alleviation of pain with a significant emotional-affective component. Our results also suggest that the mechanism of tDCS in modulating emotional pain involve pathways that are independent of those modulating the somatosensory perception of pain.     

Mesenchymal stem cells maintain the microenvironment of central nervous system by regulating the polarization of macrophages/microglia after traumatic brain injury

Mesenchymal stem cells (MSCs), which are regarded as promising candidates for cell replacement therapies, are able to regulate immune responses after traumatic brain injury (TBI). Secondary immune response following the mechanical injury is the essential factor leading to the necrosis and apoptosis of neural cells during and after the cerebral edema has subsided and there is lack of efficient agent that can mitigate such neuroinflammation in the clinical application. By means of three molecular pathways (prostaglandin E2 (PGE2), tumor-necrosis-factor-inducible gene 6 protein (TSG-6), and progesterone receptor (PR) and glucocorticoid receptors (GR)), MSCs induce the activation of macrophages/microglia and drive them polarize into the M2 phenotypes, which inhibits the release of pro-inflammatory cytokines and promotes tissue repair and nerve regeneration. The regulation of MSCs and the polarization of macrophages/microglia are dynamically changing based on the inflammatory environment. Under the stimulation of platelet lysate (PL), MSCs also promote the release of pro-inflammatory cytokines. Meanwhile, the statue of macrophages/microglia exerts significant effects on the survival, proliferation, differentiation and activation of MSCs by changing the niche of cells. They form positive feedback loops in maintaining the homeostasis after TBI to relieving the secondary injury and promoting tissue repair. MSC therapies have obtained great achievements in several central nervous system disease clinical trials, which will accelerate the application of MSCs in TBI treatment.     

Termination of reentry by a long-lasting AC shock in a slice of canine heart: a computational study

INTRODUCTION: A heart in fibrillation can be entrained by long-lasting alternating current (AC) stimuli, leading to defibrillation. To investigate the role entrainment plays in defibrillation, computer simulations of AC cardioversion in a three-dimensional slice of the canine heart were performed. METHODS AND RESULTS: A bidomain finite element model of a 1-mm thick slice across the ventricles of a canine heart was used to simulate termination of transmural reentry with AC shocks. Cardioversion defibrillation thresholds (DFTs) were determined for 200-msec (L) AC shocks at varying frequencies. At the DFT, the entire tissue is entrained by the AC shock. DFT decreases as the frequency of the long-lasting AC shock increases. We hypothesize that this decrease is due to the short period of the high-frequency AC waveform, leaving strong virtual electrode polarization (VEP) after the shock ends. To test this hypothesis, the end-shock VEP were compared for different frequencies, demonstrating stronger polarization as frequency increased. To examine whether entrainment by the long-lasting AC shock contributes to the VEP at the end of the shock, additional simulations were conducted using single-period (Z) AC waveforms. Z waveform DFTs were higher than L waveform DFTs; the Z waveform VEP was weaker than the L waveform VEP at the same frequency. This indicates that entrainment contributes to the development of stronger VEP and, thus, to lower DFT at high frequencies. CONCLUSION: This study offers for the first time a mechanistic insight into cardioversion with long-lasting AC shocks.     

Increased human erythrocyte sodium-Iithium countertransport in hyperlipidaemic patients may indicate increased membrane lipid fluidity

Abstract. Erythrocyte sodium-lithium countertransport (SLC) activity, membrane fluidity, plasma trigly-ceride and cholesterol were measured in hyperlipidaemic patients and normal subjects. Fluidity was assessed by the fluorescence anisotropy (inversely related to fluidity) of the probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,4-trimethylammonium-3,5-hexatriene (TMA-DPH). In a second group of patients the maximum velocity (Vmax) and external sodium affinity constant (k_m) of SLC was also measured.
In the first group of patients, SLC activity was increased compared with the controls (0.279 ± 0.019 vs. 0.213 ± 0.013, P = 0.006) as was membrane fluidity in the deep hydrophobic regions (DPH anisotropy 0.211 ± 0.0007 vs. 0.215 ± 0.0011, P = 0.007). There was a strong correlation between SLC and DPH anisotropy (Rs= -0.72, P= < 0.001) which was due to the correlation between Vmax and DPH anisotropy (Rs=-0.90, P= < 0.001).
Increases in Vmax of SLC in hyperlipidaemic patients may be due to differences in lipid organisation in the deep hydrophobic regions of the membrane which may affect the turnover rate of the transporter.     

Use of automatic threshold tracking function with non-low polarization leads: risk for algorithm malfunction

The AutoCapture (AC) function of new pacemakers (PM) from St Jude Medical (SJM) was originally recommended for use with low polarization (LP) ventricular leads only.However, recent reports have encouraged the use of the AC function with various leads, including those lacking a special LP design. The objective of this study was to analyze the reliability and safety of the AC algorithm application with different types of pacing leads.The study group comprised 30 consecutive patients with AC PMs connected to three different types of non-LP leads. Ten patients with SJM LP leads served as the control group. The study protocol included a complete AC function test using four different pulse widths (PW). The pacing threshold was independently assessed by a manual/semiautomatic check. Erratic behavior of polarization measurements with increasing PWs was demonstrated in 43% (n = 13) of the study group. Invalid polarization measurements resulted in erroneous algorithm recommendation to apply AC function in 17% (n = 5) of the study patients. Subsequent AC function activation lead to incorrect threshold determination due to missed noncapture in three patients. AC function should be applied with caution with non-LP leads. "Off label" use of these leads may cause erroneous polarization signal measurements which, in some cases, may result in incorrect pacing threshold determination, rendering a potential risk to dependent patients.     

CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment,but elicit divergent functional activities

Interaction trap cloning was used to identify a CD2 cytoplasmic tail-binding protein termed CD2BP3. CD2BP3 is the major RNA splice variant of the CIN85 locus in human T lymphocytes, lacking SH3A, the first of three SH3 domains found in CIN85, but retaining SH3B, SH3C, a proline-rich domain and C-terminal coiled coil. CD2BP3 has 35% amino acid identity to CMS, a structurally related protein binding to the same highly conserved segment of the CD2 tail and known to be involved in T cell polarization/cytoskeletal interactions. Unlike CMS, however, CD2BP3 does not co-localize with F-actin and binds p130(Cas) weakly, if at all. Moreover, CIN85/CD2BP3 proteins are readily degraded by TCR cross-linking, consistent with the presence of a PEST sequence C-terminal to SH3C. CIN85 SH3A and CIN85/CD2BP3 SH3B bind to proline-rich segments within CIN85/CD2BP3 themselves as evidenced by mAb accessibility analysis and protein interaction studies including c-Cbl binding. This form of intramolecular regulation is not manifest by CMS. CMS and CIN85 activities are antagonistic, while the functions of CIN85 and CD2BP3 are also distinct. Thus, CD2-mediated adhesion, signaling and cell motility are regulated in a highly complex manner.     

Imaging tissue response to electrical and photothermal stimulation with nanometer sensitivity

BACKGROUND AND OBJECTIVES: Tissue response to thermal, electrical, or chemical stimuli are important in the health and survival of tissue. We report experimental results to assess tissue response to various stimuli using a low coherence differential phase interferometer. STUDY DESIGN/MATERIALS AND METHODS: The optical system utilized to measure tissue response is a novel fiber-based phase sensitive optical low coherence reflectometer (PS-OLCR). Inasmuch as the PS-OLCR works with back-reflected light, noninvasive sensing of tissue response to stimuli is possible. In addition to high lateral (approximately 10 microm) and longitudinal (approximately 10 microm) resolution, PS-OLCR can measure sub-wavelength changes in optical path-length (Angstrom/nanometer range) by extracting the phase difference between interference fringes in two channels corresponding to orthogonal polarization modes. RESULTS: When light spatially splits into two polarization states, precise analysis of surface topography or tissue surface response such as swelling or collapse are possible. Time resolved measurements of nanometer-scale path length changes in response to electrical and thermal stimuli are demonstrated using longitudinally delayed polarization channels. CONCLUSIONS: Since PS-OLCR is a useful tool to detect ultra-small path length changes, the system has potential to aid scientists in investigating important phenomena in biomaterials and developing useful diagnostic and therapeutic imaging modalities. Applications include tissue surface profilometry, measurement of tissue, and cell response to various stimuli, high-resolution intensity and phase imaging.     

Effects of body position and exercise on evoked response signal for automatic threshold activation

The Autocapture function controls and optimizes the output of the ventricular pulse amplitude automatically. For this reason an automatic test has to be performed during follow-up to measure the evoked response signal and lead polarization for the calculation of the appropriate evoked response sensitivity setting. The aim of the study was to assess whether body position and exercise influence the evoked response and polarization. Both parameters were determined in the supine and upright position and subsequently during supine and upright symptom-limited ergometry. The study included 14 patients with the VVIR pacemaker Regency SR+ who had received the ventricular pacing leads Membrane E 1450 T (n = 8), CapSure Z 5034 (n = 4), or SX 60 (n = 2). The evoked response signal was 7.4 +/- 3.3 mV during supine and increased to 9.7 +/- 5.6 mV (+35%) during upright position (P < 0.05). The exercise tests were terminated at 105 +/- 36 W (supine) and 110 +/- 34 W (upright). There was a gradual insignificant decrease of the evoked response during each exercise test with a mean decrease of -1.1 +/- 0.9 mV (-15%; supine) and -1.6 +/- 2.1 mV (-16%; upright). The evoked response increased within 5 minutes during recovery to the initial values. Polarization remained unchanged during both tests. The pacemaker did not recommend activating autocapture in four patients who all had received high-ohmic pacing leads. In conclusions, the measurement of the evoked response in supine position seems to represent the worst case. Physical activities did not effect autocapture function in patients with the recommended lead, but the pacemaker did not always recommend Autocapture activation in some patients with high-ohmic pacing leads.     

On the physical properties of red cell ghost membranes in the affective disorders and psychoses A fluorescence polarization study

Membrane order was measured in the erythrocyte ghost membranes of DSM-III schizophreniform disorder (SF), DSM-III schizophrenic (SCZ) and DSM-III manic (bipolar) (M) patients and a group of age- and sex-matched controls. Fluorescence polarization with the probe 1,6-diphenyl1-1,3,5-hexatriene was used to determine the steady-state fluorescence anisotropy (r_s). The SF group showed a significant increase in r_s (Δr_s = 0.037) from the control group. Although the means were not significantly different, 3 of 8 Ms and 5 of 8 SCZs also had r_s values > the highest control value. Thermotropic behavior of the membranes was evaluated over the range of 40 to 20°C. No difference among groups in membrane enthalpy was detected. Thus, the differences in r_s appear to be associated with differences in entropy. Phosphatidylcholine (PC) levels, which were known to be abnormal in these patients, were compared with the r_s values. A significant (P < 0.001, R= -0.63) linear correlation between r_s and membrane PC levels was observed. Overall these data further support the view that unusual membrane biophysical factors may occur with high frequency in the psychoses and affective disorders.