The potential role of temporal dynamics in approach biases: delay-dependence of a general approach bias in an alcohol approach-avoidance task

Attractive cues have been shown to evoke automatic approach biases in tasks such as the Automatic Approach Task or Stimulus Response Compatibility task. An important but as yet not studied question is the role of temporal dynamics in such tasks: the impact of automatic processes may depend on the interval between cue and response. The current proof of principle study tested this hypothesized time-dependence of the approach bias. Secondary goals included the exploration of effects of alcohol cues and virtual hand stimuli. 22 participants performed an SRC task in which the delay between the presentation of the cue and the possibility to select the response was manipulated. Results revealed an approach bias that decayed over longer delays. Thus, the approach bias was indeed dependent on processes that are transiently evoked by cues. The results did not show significant effects of alcohol cues or a virtual hand. Temporal dynamics may be an essential feature of approach biases

A Clinical Trial with Combined Transcranial Direct Current Stimulation and Attentional Bias Modification in Alcohol Dependent Patients

Modifying attentional processes with attentional bias modification (ABM) might be a relevant add-on to treatment in addiction. This study investigated whether influencing cortical plasticity with transcranial direct current stimulation (tDCS) could increase training effects. tDCS could also help alcohol-dependent patients to overcome craving and reduce relapse, independent of training. These approaches were combined to investigate effects in the treatment of alcoholism. Ninety-eight patients (analytical sample = 83) were randomly assigned to 4 groups in a 2-by-2 factorial design. Patients received 4 sessions of ABM (control or real training) combined with 2 mA tDCS (active: 20 minutes or sham: 30 seconds) over the left dorsolateral prefrontal cortex. Alcohol bias and craving were assessed, and treatment outcome was measured as relapse after 1 year. Attentional bias scores indicated that during the training only the group with active tDCS and real ABM displayed an overall avoidance bias (p  0.2). However, effects on relapse after active tDCS were in the expected direction. There was no evidence of a beneficial effect of tDCS or ABM or the combination. Whether the absence of effect was due to issues with the outcome measurements (e.g., lack of craving, high dropout, and unreliable measurements) or aspects of the intervention should be further investigated. [Abstract copyright: © 2018 The Authors Alcoholism: Clinical & Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.

Training Working Memory in Adolescents Using Serious Game Elements: Pilot Randomized Controlled Trial

Working memory capacity has been found to be impaired in adolescents with various psychological problems, such as addictive behaviors. Training of working memory capacity can lead to significant behavioral improvements, but it is usually long and tedious, taxing participants' motivation to train. This study aimed to evaluate whether adding game elements to the training could help improve adolescents' motivation to train while improving cognition. A total of 84 high school students were allocated to a working memory capacity training, a gamified working memory capacity training, or a placebo condition. Working memory capacity, motivation to train, and drinking habits were assessed before and after training. Self-reported evaluations did not show a self-reported preference for the game, but participants in the gamified working memory capacity training condition did train significantly longer. The game successfully increased motivation to train, but this effect faded over time. Working memory capacity increased equally in all conditions but did not lead to significantly lower drinking, which may be due to low drinking levels at baseline. We recommend that future studies attempt to prolong this motivational effect, as it appeared to fade over time. [Abstract copyright: ©Wouter J Boendermaker, Thomas E Gladwin, Margot Peeters, Pier JM Prins, Reinout W Wiers. Originally published in JMIR Serious Games (http://games.jmir.org), 23.05.2018.

Exact quantization of a PT-symmetric (reversible) Li\'enard-type nonlinear oscillator

We carry out an exact quantization of a PT symmetric (reversible) Li\'{e}nard type one dimensional nonlinear oscillator both semiclassically and quantum mechanically. The associated time independent classical Hamiltonian is of non-standard type and is invariant under a combined coordinate reflection and time reversal transformation. We use von Roos symmetric ordering procedure to write down the appropriate quantum Hamiltonian. While the quantum problem cannot be tackled in coordinate space, we show how the problem can be successfully solved in momentum space by solving the underlying Schr\"{o}dinger equation therein. We obtain explicitly the eigenvalues and eigenfunctions (in momentum space) and deduce the remarkable result that the spectrum agrees exactly with that of the linear harmonic oscillator, which is also confirmed by a semiclassical modified Bohr-Sommerfeld quantization rule, while the eigenfunctions are completely different.Comment: 10 pages, 1 figure, Fast Track Communicatio

994-99 Can Late Saphenous Vein Graft Closure Be Predicted by Quantitative Angiographic Analysis Before the Clinical Event?

Angiographic parameters predicting the likelihood of late occlusion of saphenous vein grafts (SVG) have been infrequently described. The Post-CABG Study, a 5-year trial aimed at reducing SVG closure in minimally symptomatic patients 1–11 years Post-CABG, offers a unique view into this event since this study requires an angiogram to document baseline graft patency. In this preliminary study we performed quantitative angiographic analysis (QAA Reiber) comparing the baseline Post-CABG study angiogram to an unscheduled “clinically driven” angiogram. Of 1253 enrolled patients with at least one patent SVG, 35 developed MI or unstable angina associated angiographically with a changed SVG lesion and either total or subtotal occlusion. Average patient age was 58±2 (SEM)years; 97% were male. Years since SVG placement to baseline angiogram averaged 6.5±0.4 (range 2–14). Time from the baseline to the unscheduled angiogram was 22±2 mo (range 3–47). In 28 patients the involved graft was single and in 7 sequential. The SVG insertion segments involved the LCX in 17, RCA in 15 and LAD in 10.ResultsThe initial lesion diameter at the site of the subsequent inciting lesion for all 35 patients averaged 2.58±0.17 mm, or 29.5±3.6% diam. stenosis. (This was defined as the most severe stenosis in any part of the graft in patients with subsequent total graft occlusion, and the exactly matched graft site in those with subtotal occlusion.) In 8 patients the baseline SVG was entirely normal. The initial lesion was >50% stenosis in only 4 patients. At the time of the clinical event, the lesion had progressed to 87±2.6% diam stenosis (N=35). In 16 patients the causal lesion was subtotal, while in 19 the SVG was totally occluded. The mean native vessel — responsible graft anastomotic diameter was 2.33±0.12mm.ConclusionQAA of SVG in asymptomatic patients may not predict subsequent graft closure associated with acute coronary syndromes. The initial site of the lesion is typically of mild-moderate severity, and only later exhibits rapid progression to occlusion

Mechanisms of Hemolysis-Associated Platelet Activation

Background Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias, and in other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo, and several mechanisms have been suggested to account for this, including: (i) direct activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS); (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of intraerythrocytic ADP. Objective To elucidate the mechanism of hemolysis-mediated platelet activation. Methods We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments, and a Siemens\u27 Advia 120 hematology system to assess platelet aggregation by using platelet counts from in vivo experiments in a rodent model. Results We found that Hb did not directly activate platelets. However, ADP bound to Hb could cause platelet activation. Furthermore, platelet activation caused by shearing of red blood cells (RBCs) was reduced in the presence of apyrase, which metabolizes ADP to AMP. The use of ROS scavengers did not affect platelet activation. We also found that cell-free Hb enhanced platelet activation by abrogating the inhibitory effect of NO on platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb, as well as hemolysate, resulted in platelet aggregation, as shown by decreased platelet counts. Conclusion Two primary mechanisms account for RBC hemolysis-associated platelet activation: ADP release, which activates platelets; and cell-free Hb release, which enhances platelet activation by lowering NO bioavailability

Nonlocal symmetries of a class of scalar and coupled nonlinear ordinary differential equations of any order

In this paper we devise a systematic procedure to obtain nonlocal symmetries of a class of scalar nonlinear ordinary differential equations (ODEs) of arbitrary order related to linear ODEs through nonlocal relations. The procedure makes use of the Lie point symmetries of the linear ODEs and the nonlocal connection to deduce the nonlocal symmetries of the corresponding nonlinear ODEs. Using these nonlocal symmetries we obtain reduction transformations and reduced equations to specific examples. We find the reduced equations can be explicitly integrated to deduce the general solutions for these cases. We also extend this procedure to coupled higher order nonlinear ODEs with specific reference to second order nonlinear ODEs.Comment: Accepted for publication in J. Phys. A Math. Theor. 201

A Tale of Three Cities : OmegaCAM discovers multiple sequences in the color-magnitude diagram of the Orion Nebula Cluster

Reproduced with permission from Astronomy & Astrophysics, © 2017 ESO. Published by EDP Sciences.As part of the Accretion Discs in H$\alpha$ with OmegaCAM (ADHOC) survey, we imaged in r, i and H-alpha a region of 12x8 square degrees around the Orion Nebula Cluster. Thanks to the high-quality photometry obtained, we discovered three well-separated pre-main sequences in the color-magnitude diagram. The populations are all concentrated towards the cluster's center. Although several explanations can be invoked to explain these sequences we are left with two competitive, but intriguing, scenarios: a population of unresolved binaries with an exotic mass ratio distribution or three populations with different ages. Independent high-resolution spectroscopy supports the presence of discrete episodes of star formation, each separated by about a million years. The stars from the two putative youngest populations rotate faster than the older ones, in agreement with the evolution of stellar rotation observed in pre-main sequence stars younger than 4 Myr in several star forming regions. Whatever the final explanation, our results prompt for a revised look at the formation mode and early evolution of stars in clusters.Peer reviewedFinal Published versio

Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer

Nitrite (NO2−) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed (24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury. This cytoprotection is associated with increases in mitochondrial oxidative phosphorylation. Remarkably, isolated mitochondria subjected to 30 min of anoxia followed by reoxygenation were directly protected by nitrite administered both in vitro during anoxia or in vivo 24 h before mitochondrial isolation. Mechanistically, nitrite dose-dependently modifies and inhibits complex I by posttranslational S-nitrosation; this dampens electron transfer and effectively reduces reperfusion reactive oxygen species generation and ameliorates oxidative inactivation of complexes II–IV and aconitase, thus preventing mitochondrial permeability transition pore opening and cytochrome c release. These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al