Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation

Astrocytes are responsible for regulating extracellular levels of glutamate and potassium during neuronal activity. Glutamate clearance is handled by glutamate transporter subtypes glutamate transporter 1 and glutamate-aspartate transporter in astrocytes. DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate (DHK) are extensively used as inhibitors of glial glutamate transport activity. Using whole-cell recordings, we characterized the effects of both transporter inhibitors on afferent-evoked astrocyte currents in acute cortical slices of 3-week-old rats. When neuronal afferents were stimulated, passive astrocytes responded by a rapid inward current followed by a persistent tail current. The first current corresponded to a glutamate transporter current. This current was inhibited by both inhibitors and by tetrodotoxin. The tail current is an inward potassium current as it was blocked by barium. Besides inhibiting transporter currents, TBOA strongly enhanced the tail current. This effect was barium-sensitive and might be due to a rise in extracellular potassium level and increased glial potassium uptake. Unlike TBOA, DHK did not enhance the tail current but rather inhibited it. This result suggests that, in addition to inhibiting glutamate transport, DHK prevents astrocyte potassium uptake, possibly by blockade of inward-rectifier channels. This study revealed that, in brain slices, glutamate transporter inhibitors exert complex effects that cannot be attributed solely to glutamate transport inhibition.

Suivi du patient oncologique, garant de la permanence de soi [Follow-up of the cancer patient, maintaining self-identity]

L'individu confronté au diagnostic de cancer subit un bouleversement brutal de ses repères et de ses habitudes. La maladie représente une menace pour son équilibre de vie et sa stabilité sociale. Sa capacité à faire face et à opérer différents remaniements dans sa façon d'être au monde et d'envisager l'avenir est en partie déterminée par ses ressources personnelles. Toutefois, le soutien émotionnel peut également représenter un moyen privilégié de donner du sens à cette expérience singulière qu'est la maladie. La reconstruction narrative dans un cadre soutenant, caractérisé par une écoute bienveillante, offre au patient la possibilité de reconnaître sa souffrance comme partie intégrante de lui-même. Un récit de vie qui intègre la maladie lui permet de se réapproprier son histoire. Cette démarche nécessite de la part du thérapeute une disponibilité psychique et temporelle et la capacité de soutenir le patient dans un processus de liaison à travers les différentes étapes de la maladie. The individual facing the diagnosis of cancer is subjected to abrupt changes with regard to his inner world, his life, habits and social relationships. The patient's capacity to cope, to integrate changes in the way of living and to face the future is determined by his personal resources. However, psychological support may also be an important mean to search for and find sense to the singular experience of the illness. The narrative reconstruction within a supportive setting provides the patient a possibility to recognise his sufferance as an integral part of himself. A life narrative, which integrates the illness, allows the patient to re-appropriate his history again. Such a therapeutic project necessitates from the therapist a psychological and temporal disponibility and a capacity to create links all along the different stages of the disease.

Twitch and M-wave potentiation induced by intermittent maximal voluntary quadriceps contractions: Differences between direct quadriceps and femoral nerve stimulation.

Introduction: To investigate differences in twitch and M-wave potentiation in the quadriceps femoris when electrical stimulation is applied over the quadriceps muscle belly versus the femoral nerve trunk. Methods: M-waves and mechanical twitches were evoked using direct quadriceps muscle and femoral nerve stimulation between 48 successive isometric maximal voluntary contractions (MVC) from 10 young, healthy subjects. Potentiation was investigated by analyzing the changes in M-wave amplitude recorded from the vastus medialis (VM) and vastus lateralis (VL) muscles and in quadriceps peak twitch force. Results: Potentiation of twitch, VM M-wave, and VL M-wave were greater for femoral nerve than for direct quadriceps stimulation (P<0.05). Despite a 50% decrease in MVC force, the amplitude of the M-waves increased significantly during exercise. Conclusions: In addition to enhanced electrogenic Na(+) -K(+) pumping, other factors (such as synchronization in activation of muscle fibers and muscle architectural properties) might significantly influence the magnitude of M-wave enlargement. © 2013 Wiley Periodicals, Inc.

Traitement des epilepsies réfractaires: rôle de la stimulation electrique [Treatment of pharmacoresistant epilepsy: stimulated refractoriness].

Antiepileptic drugs allow controlling seizures in 70% of patients. For the others, a presurgical work-up should be undertaken, especially if a focal seizure origin is suspected; however, only a fraction of pharmacoresistant patients will be offered resective (curative) surgery. In the last 15 years, several palliative therapies using extra- or intracranial electrical stimulations have been developed. This article presents the vagal nerve stimulation, the deep brain stimulation (targeting the mesiotemporal region or the thalamus), and the cortical stimulation "on demand". All show an overall long-term responder rate between 30-50%, but less than 5% of patients becoming seizure free. It is to hope that a better understanding of epileptogenic mechanisms and of the implicated neuronal networks will lead to an improvement of these proportions.

The gain-loss asymmetry and single-self preferences

Kahneman and Tversky asserted a fundamental asymmetry between gains and losses, namely a reflection effect which occurs when an individual prefers a sure gain of $ pz to anuncertain gain of $ z with probability p, while preferring an uncertain loss of $z with probability p to a certain loss of $ pz.We focus on this class of choices (actuarially fair), and explore the extent to which thereflection effect, understood as occurring at a range of wealth levels, is compatible with single-self preferences.We decompose the reflection effect into two components, a probability switch effect,which is compatible with single-self preferences, and a translation effect, which is not. To argue the first point, we analyze two classes of single-self, nonexpected utility preferences, which we label homothetic and weakly homothetic. In both cases, we characterize the switch effect as well as the dependence of risk attitudes on wealth.We also discuss two types of utility functions of a form reminiscent of expected utility but with distorted probabilities. Type I always distorts the probability of the worst outcome downwards, yielding attraction to small risks for all probabilities. Type II distorts low probabilities upwards, and high probabilities downwards, implying risk aversion when the probability of the worst outcome is low. By combining homothetic or weak homothetic preferences with Type I or Type II distortion functions, we present four explicit examples: All four display a switch effect and, hence, a form of reflection effect consistent a single self preferences.

Are tax subsidies for private medical insurance self-financing? Evidence from a microsimulation model for outpatient and inpatient episodes

This paper analyses whether or not tax subsidies to private medicalinsurance are self-financing by means of a structural approach. Weconstruct a simulation routine based on a microeconometric discretechoice model that allows us to evaluate the impact of premium changeson the utilisation of outpatient and inpatient health care services. Wesimulate the 1999 Spanish tax reform that abolished the tax deductionfor expenditures on private health insurance using a representativesample of the Catalan population. Prior to this reform, foregone taxrevenue arising from deductions after the purchase of private insuranceamounted to 69.2 M. per year. In contrast, the elimination of thesubsidies to private policies is estimated to generate an extra costfor the public sector of about 8.9 M. per year.

Respiration, metabolic balance, and attention in affective picture processing

The jointly voluntary and involuntary control of respiration, unique among essential physiological processes, the interconnection of breathing with and its influence on the autonomic nervous system, and disease states associated with the interface between psychology and respiration (e.g., anxiety disorders, hyperventilation syndrome, asthma) make the study of the relationship between respiration and emotion both theoretically and clinically of great relevance. However, the respiratory behavior during affective states is not yet completely understood. We studied breathing pattern responses to 13 picture series varying widely in their affective tone in 37 adults (18 men, 19 women, mean age 26). Time and volume parameters were recorded with the LifeShirt system (VivoMetrics Inc., Ventura, California, USA, see image). We also measured end-tidal pCO2 (EtCO2) with a Microcap Handheld Capnograph (Oridion Medical 1987 Ltd., Jerusalem, Israel) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. At the end of each picture series, the participants reported their subjective feeling in the affective dimensions of pleasantness and arousal. Increasing self-rated arousal was associated with increasing minute ventilation but not with decreases in EtCO2, suggesting that ventilatory changes during picture viewing paralleled variations in metabolic activity. EtCO2 correlated with pleasantness, and eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. Like MV, inspiratory drive (i.e., mean inspiratory flow) increased with arousal. This relationship reflected increases in inspiratory volume rather than shortening of the time parameters. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of pleasantness and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal. Finally, end-tidal pCO2 is slightly lower during processing of negative as compared to positive picture contents, which is proposed to enhance sensory perception and reflect a negativity bias in attention.

Self-paced Movement Intention Detection from Human Brain Signals: Invasive and Non-invasive EEG

Neural signatures of humans' movement intention can be exploited by future neuroprosthesis. We propose a method for detecting self-paced upper limb movement intention from brain signals acquired with both invasive and noninvasive methods. In the first study with scalp electroencephalograph (EEG) signals from healthy controls, we report single trial detection of movement intention using movement related potentials (MRPs) in a frequency range between 0.1 to 1 Hz. Movement intention can be detected above chance level (p<0.05) on average 460 ms before the movement onset with low detection rate during the on-movement intention period. Using intracranial EEG (iEEG) from one epileptic subject, we detect movement intention as early as 1500 ms before movement onset with accuracy above 90% using electrodes implanted in the bilateral supplementary motor area (SMA). The coherent results obtained with non-invasive and invasive method and its generalization capabilities across different days of recording, strengthened the theory that self-paced movement intention can be detected before movement initiation for the advancement in robot-assisted neurorehabilitation.

Precursors of functional MHC class I- or class II-restricted CD8alphaalpha(+) T cells are positively selected in the thymus by agonist self-peptides.

The origin and specificity of alphabeta TCR(+) T cells that express CD8alphaalpha have been controversial issues. Here we provide direct evidence that precursors of functional CD8alphaalpha T cells are positively selected in the thymus in the presence of agonist self-peptides. Like conventional positive selection, this agonist selection process requires functional TCR alpha-CPM, whereas it is independent of CD8beta expression. Furthermore, CD8alphaalpha expression on mature, agonist-selected T cells does not imply selection by MHC class I, and CD8alphaalpha(+) T cells can be either class I or class II restricted. Our data define a distinct agonist-dependent, positive selection process in the thymus, and they suggest a function for CD8alphaalpha distinct from the conventional TCR coreceptor function of CD8alphabeta or CD4.

Concentration and self-censorship in commercial media

Within a simple model of non-localized, Hotelling-type competitionamong arbitrary numbers of media outlets we characterize qualityand content of media under different ownership structures. Assumingadvertising-sponsored, profit-maximizing outlets, we show that (i) topicssensitive to advertisers can be underreported (self-censored) by alloutlets in the market, (ii) self-censorship increases with the concentrationof ownership, (iii) adding outlets, while keeping the number ofowners fixed, may even increase self-censorship; the latter result relieson consumers' most preferred outlets being potentially owned by thesame media companies. We argue that externalities resulting fromself-censorship could be empirically large.

Family Development and Self-Sufficiency Program, Annual Report, 2008

Iowa’s Family Development and Self-Sufficiency (FaDSS) Grant Program was created by the 1988 Iowa General Assembly to assist Family Investment Program (FIP) families with significant or multiple barriers reach self-sufficiency. FaDSS provides services that promote, empower, and nurture families towards economic and emotional self-sufficiency. The foundation of FaDSS is regular home visits with families, using a strength-based approach. Core services include support, goal setting, and assessment. Support is given in many ways such as referrals, group activities, linking families to communities and advocacy. Assessment aids the family to identify strengths that they possess that may be used to eliminate barriers to self-sufficiency. Goal setting helps families break down goals that seem out of reach into small steps that will lead to success. Participation in FaDSS is a voluntary option for people receiving Family Investment Program (FIP) benefits.