Comparison of NRT based MAPs and preferred MAPs in adult Nucleus CI24 cochlear implant users

Comparison of subjects' preferred MAPs worn in everyday life and MAPs created using electrically evoked compound action potentials using neural response telemetry measures in adult Nucleus CI24 implant users.

Neural response telemetry in patients with the double-array cochlear implant

This study aimed to evaluate the neural response in double-array cochlear implant as well as to describe the refractory recovery and the spread of excitation functions. In a prospective study 11 patients were implanted with the double-array cochlear implant. Neural response telemetry (NRT) was performed intra-operatively. NRT threshold could be registered in 6 of the 11 patients, at least in one electrode. The remaining five patients did not show measurable neural response intra-operatively. It was noted that although recovery and spread of excitation functions could be recorded in all the tested electrodes with measurable neural responses, the responses were shown to be different from the usual register in patients with other etiologies.

The effectiveness of personalized smoking cessation strategies for callers to a Quitline service

Aim To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation. Design Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months. Setting Victoria, Australia. Participants A total of 1578 smokers who called the Quitline service and agreed to participate. Measurements Smoking status at follow-up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service. Findings At the 3-month follow-up, significantly more (chi(2)(2) = 16.9; P < 0.001) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer-generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12-month follow-up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer-generated tailored advice. Conclusion Computer-generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice.

Avaliação longitudinal do ECAP registrado em crianças usuárias de implante coclear

Em crianças usuárias de Implante Coclear (IC), o registro do potencial de ação composto do nervo auditivo evocado eletricamente (ECAP) representa uma maneira de avaliar as modificações nas respostas neurais e entre o feixe de eletrodos e o tecido neural ao longo do tempo. OBJETIVO: Estudar o ECAP em crianças ao longo do primeiro ano de uso do IC. MATERIAL E MÉTODO: As características do ECAP foram analisadas em 13 crianças, implantadas com idades inferiores a três anos de idade. Estudo de série. RESULTADOS: Houve aumento estatisticamente significante na amplitude do pico N1, nos eletrodos basais, entre o segundo e o terceiro retorno. Não foram obtidas diferenças significantes para: a latência do pico N1, o slope, o p-NRT e o período de recuperação entre os retornos. Nos três retornos, a maioria dos sujeitos apresentou tempo de recuperação entre 1000 e 2000µs. CONCLUSÃO: Ao longo do primeiro ano de uso do IC, a estimulação elétrica liberada pelos eletrodos intracocleares não causou alterações significativas às características do ECAP, exceto pelo aumento da amplitude do pico N1.

T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.

T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.

Sleep spindles are synchronized 11-15 Hz electroencephalographic (EEG) oscillations predominant during nonrapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Ca(v)3.3-type Ca(2+) channels and Ca(2+)-dependent small-conductance-type 2 (SK2) K(+) channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-overexpressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared with wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow waves (<4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles.

Every cigarette is doing you damage

This leaflet explains the dangers of smoking and why you should stop. It also provides information on nicotine replacement therapy (NRT) and non-nicotine treatments as well as other sources of help and advice.

Phasic, nonsynaptic GABA-A receptor-mediated inhibition entrains thalamocortical oscillations.

GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs. In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically during burst firing of nRT cells and provide sufficient GABA-AR activation to control major thalamocortical oscillations.

Stopping smoking made easier (English and translations)

This booklet takes smokers through the stages of stopping smoking:preparing to stopstoppingstaying stoppedIt also provides advice on the various forms of nicotine replacement therapy (NRT) and non-nicotine medications available, as well as a list of contacts for advice and support.Note: translations are of the 2009 leaflet, which will have lower costs for packets of cigarettes.

Smoking: know the facts

This leaflet outlines the health and financial benefits of stopping smoking. It provides key facts on the health dangers associated with smoking, information on second-hand smoke, information on the dangers of smoking to babies, and contact details for help and support available. It also lists the various forms of nicotine replacement therapy (NRT) and non-nicotine medications available.This poster highlights some of the main health and financial benefits of stopping smoking. An associated A5 leaflet goes into detail on these areas.

The Ca(V)3.3 calcium channel is the major sleep spindle pacemaker in thalamus.

Low-threshold (T-type) Ca(2+) channels encoded by the Ca(V)3 genes endow neurons with oscillatory properties that underlie slow waves characteristic of the non-rapid eye movement (NREM) sleep EEG. Three Ca(V)3 channel subtypes are expressed in the thalamocortical (TC) system, but their respective roles for the sleep EEG are unclear. Ca(V)3.3 protein is expressed abundantly in the nucleus reticularis thalami (nRt), an essential oscillatory burst generator. We report the characterization of a transgenic Ca(V)3.3(-/-) mouse line and demonstrate that Ca(V)3.3 channels are indispensable for nRt function and for sleep spindles, a hallmark of natural sleep. The absence of Ca(V)3.3 channels prevented oscillatory bursting in the low-frequency (4-10 Hz) range in nRt cells but spared tonic discharge. In contrast, adjacent TC neurons expressing Ca(V)3.1 channels retained low-threshold bursts. Nevertheless, the generation of synchronized thalamic network oscillations underlying sleep-spindle waves was weakened markedly because of the reduced inhibition of TC neurons via nRt cells. T currents in Ca(V)3.3(-/-) mice were <30% compared with those in WT mice, and the remaining current, carried by Ca(V)3.2 channels, generated dendritic [Ca(2+)](i) signals insufficient to provoke oscillatory bursting that arises from interplay with Ca(2+)-dependent small conductance-type 2 K(+) channels. Finally, naturally sleeping Ca(V)3.3(-/-) mice showed a selective reduction in the power density of the σ frequency band (10-12 Hz) at transitions from NREM to REM sleep, with other EEG waves remaining unaltered. Together, these data identify a central role for Ca(V)3.3 channels in the rhythmogenic properties of the sleep-spindle generator and provide a molecular target to elucidate the roles of sleep spindles for brain function and development.

THE ROLE OF SPINDLES FOR SLEEP: MANIPULATING OSCILLATORY ACTIVITY IN THE THALAMOCORTICAL NETWORK

Modern urban lifestyle encourages the prolongation of wakefulness, leaving less and less time for sleep. Although the exact functions of sleep remain one of the biggest mysteries in neuroscience, the society is well aware of the negative consequences of sleep loss on human physical and mental health and performance. Enhancing sleep's recuperative functions might allow shortening sleep duration while preserving the beneficial effects of sleep. During sleep, brain activity oscillates across a continuum of frequencies. Individual oscillations have been suggested to underlie distinct functions for sleep and cognition. Gaining control about individual oscillations might allow boosting their specific functions. Sleep spindles are 11 - 15 Hz oscillations characteristic for light non-rapid-eye-movement sleep (NREMS) and have been proposed to play a role in memory consolidation and sleep protection against environmental stimuli. The reticular thalamic nucleus (nRt) has been identified as the major pacemaker of spindles. Intrinsic oscillatory burst discharge in nRt neurons, arising from the interplay of low-threshold (T-type) Ca2+ channels (T channels) and small conductance type 2 (SK2) K+ channels (SK2 channels), underlies this pacemaking function. In the present work we investigated the impact of altered nRt bursting on spindle generation during sleep by studying mutant mice for SK2 channels and for CaV3.3 channels, a subtype of T channels. Using in vitro electrophysiology I showed that nRt bursting was abolished in CaV3.3 knock out (CaV3.3 KO) mice. In contrast, in SK2 channel over-expressing (SK2-OE) nRt cells, intrinsic repetitive bursting was prolonged. Compared to wildtype (WT) littermates, altered nRt burst discharge lead to weakened thalamic network oscillations in vitro in CaV3.3 KO mice, while oscillatory activity was prolonged in SK2-OE mice. Sleep electroencephalographic recordings in CaV3.3 KO and SK2-OE mice revealed that reduced or potentiated nRt bursting respectively weakened or prolonged sleep spindle activity at the NREMS - REMS transition. Furthermore, SK2-OE mice showed more consolidated NREMS and increased arousal thresholds, two correlates of good sleep quality. This thesis work suggests that CaV3.3 and SK2 channels may be targeted in order to modulate sleep spindle activity. Furthermore, it proposes a novel function for spindles in NREMS consolidation. Finally, it provides evidence that sleep quality may be improved by promoting spindle activity, thereby supporting the hypothesis that sleep quality can be enhanced by modulating oscillatory activity in the brain. Le style de vie moderne favorise la prolongation de l'éveil, laissant de moins en moins de temps pour le sommeil. Même si le rôle exact du sommeil reste un des plus grands mystères des neurosciences, la société est bien consciente des conséquences négatives que provoque un manque de sommeil, à la fois sur le plan de la santé physique et mentale ainsi qu'au niveau des performances cognitives. Augmenter les fonctions récupératrices du sommeil pourrait permettre de raccourcir la durée du sommeil tout en en conservant les effets bénéfiques. Durant le sommeil, on observe des oscillations à travers un continuum de fréquences. Il a été proposé que chaque oscillation pourrait être à l'origine de fonctions spécifiques pour le sommeil et la cognition. Pouvoir de contrôler les oscillations individuelles permettrait d'augmenter leurs fonctions respectives. Les fuseaux sont des oscillations de 11 à 15 Hz caractéristiques du sommeil à ondes lentes léger et il a été suggéré qu'elles jouent un rôle majeur pour la consolidation de la mémoire ainsi que dans la protection du sommeil contre les stimuli environnementaux. Le nucleus réticulaire du thalamus (nRt) a été identifié en tant que générateur de rythme des fuseaux. Les bouffées oscillatoires intrinsèques des neurones du nRt, provenant de l'interaction de canaux calciques à bas seuil de type T (canaux T) et de canaux potassiques à faible conductance de type 2 (canaux SK2), sont à l'origine de la fonction de générateur de rythme. Dans ce travail, j'ai étudié l'impact de la modulation de bouffées de nRT sur la génération des fuseaux pendant le sommeil en investiguant des souris génétiquement modifiées pour les canaux SK2 et les canaux CaV3.3, un sous-type de canaux T. En utilisant l'électrophysiologie in vitro j'ai démontré que les bouffées du nRT étaient abolies dans les souris knock-out du type CaV3.3 (CaV3.3 KO). D'autre part, dans les cellules nRT sur-exprimant les canaux SK2 (SK2-OE), les bouffées oscillatoires intrinsèques étaient prolongées. Par rapport aux souris wild type, les souris CaV3.3 KO ont montré un affaiblissement des oscillations thalamiques en réponse à un changement des bouffées de nRT, alors que l'activité oscillatoire était prolongée dans les souris SK2-OE. Des enregistrements EEG du sommeil dans des souris de type CaV3.3 KO et SK2-OE ont révélé qu'une réduction ou augmentation des bouffées nRT ont respectivement affaibli ou prolongé l'activité des fuseaux durant les transitions du sommeil à ondes lentes au sommeil paradoxal. De plus, les souris SK2-OE ont montré des signes de consolidation du sommeil à ondes lentes et un seuil augmenté pour le réveil, deux mesures qui corrèlent avec une bonne qualité du sommeil. Le travail de cette thèse propose que les canaux CaV3.3 et SK2 pourrait être ciblés pour moduler l'activité des fuseaux. De plus, je propose une fonction nouvelle pour les fuseaux dans la consolidation du sommeil à ondes lentes. Finalement je suggère que la qualité du sommeil peut être améliorée en promouvant l'activité des fuseaux, soutenant ainsi l'idée que la qualité du sommeil peut être améliorée en modulant l'activité oscillatoire dans le cerveau.

Contrasting the functional properties of GABAergic axon terminals with single and multiple synapses in the thalamus

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one "extrareticular" input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The contrasting synaptic arrangements of the two pathways were paralleled by different short-term plasticities. The multisite APT-thalamic pathway showed larger charge transfer during 50-100 Hz stimulation compared with the nRT pathway and a greater persistent inhibition accruing during stimulation trains. Our results demonstrate that the two inhibitory systems are morpho-functionally distinct and suggest and that multisite GABAergic terminals are tailored for maintained synaptic inhibition even at high presynaptic firing rates. These data explain the efficacy of extrareticular inhibition in timing relay cell activity in sensory and motor thalamic nuclei. Finally, based on the classic nomenclature and the difference between reticular and extrareticular terminals, we define a novel, multisite GABAergic terminal type (F3) in the thalamus.

Interventions for smoking cessation in hospitalised patients.

BACKGROUND: Smoking contributes to reasons for hospitalisation, and the period of hospitalisation may be a good time to provide help with quitting. OBJECTIVES: To determine the effectiveness of interventions for smoking cessation that are initiated for hospitalised patients. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group register which includes papers identified from CENTRAL, MEDLINE, EMBASE and PsycINFO in December 2011 for studies of interventions for smoking cessation in hospitalised patients, using terms including (hospital and patient*) or hospitali* or inpatient* or admission* or admitted. SELECTION CRITERIA: Randomized and quasi-randomized trials of behavioural, pharmacological or multicomponent interventions to help patients stop smoking, conducted with hospitalised patients who were current smokers or recent quitters (defined as having quit more than one month before hospital admission). The intervention had to start in the hospital but could continue after hospital discharge. We excluded studies of patients admitted to facilities that primarily treat psychiatric disorders or substance abuse, studies that did not report abstinence rates and studies with follow-up of less than six months. Both acute care hospitals and rehabilitation hospitals were included in this update, with separate analyses done for each type of hospital. DATA COLLECTION AND ANALYSIS: Two authors extracted data independently for each paper, with disagreements resolved by consensus. MAIN RESULTS: Fifty trials met the inclusion criteria. Intensive counselling interventions that began during the hospital stay and continued with supportive contacts for at least one month after discharge increased smoking cessation rates after discharge (risk ratio (RR) 1.37, 95% confidence interval (CI) 1.27 to 1.48; 25 trials). A specific benefit for post-discharge contact compared with usual care was found in a subset of trials in which all participants received a counselling intervention in the hospital and were randomly assigned to post-discharge contact or usual care. No statistically significant benefit was found for less intensive counselling interventions. Adding nicotine replacement therapy (NRT) to an intensive counselling intervention increased smoking cessation rates compared with intensive counselling alone (RR 1.54, 95% CI 1.34 to 1.79, six trials). Adding varenicline to intensive counselling had a non-significant effect in two trials (RR 1.28, 95% CI 0.95 to 1.74). Adding bupropion did not produce a statistically significant increase in cessation over intensive counselling alone (RR 1.04, 95% CI 0.75 to 1.45, three trials). A similar pattern of results was observed in a subgroup of smokers admitted to hospital because of cardiovascular disease (CVD). In this subgroup, intensive intervention with follow-up support increased the rate of smoking cessation (RR 1.42, 95% CI 1.29 to 1.56), but less intensive interventions did not. One trial of intensive intervention including counselling and pharmacotherapy for smokers admitted with CVD assessed clinical and health care utilization endpoints, and found significant reductions in all-cause mortality and hospital readmission rates over a two-year follow-up period. These trials were all conducted in acute care hospitals. A comparable increase in smoking cessation rates was observed in a separate pooled analysis of intensive counselling interventions in rehabilitation hospitals (RR 1.71, 95% CI 1.37 to 2.14, three trials). AUTHORS' CONCLUSIONS: High intensity behavioural interventions that begin during a hospital stay and include at least one month of supportive contact after discharge promote smoking cessation among hospitalised patients. The effect of these interventions was independent of the patient's admitting diagnosis and was found in rehabilitation settings as well as acute care hospitals. There was no evidence of effect for interventions of lower intensity or shorter duration. This update found that adding NRT to intensive counselling significantly increases cessation rates over counselling alone. There is insufficient direct evidence to conclude that adding bupropion or varenicline to intensive counselling increases cessation rates over what is achieved by counselling alone.

Medical and pharmacological direct costs of a 9-week smoking cessation programme.

Background: Medical and pharmacological direct costs of cigarette smoking cessation programmes are not covered by health insurance in several countries despite documented cost-effectiveness. Design: prospective cost identification study of a 9-week programme in Switzerland. Methods: A total of 481 smokers were followed-up for 9 weeks. Socio-demographic characteristics, number of outpatient visits, dosage and frequency of use of nicotine replacement therapy (NRT) as well as date of relapse were prospectively collected. Individual cost of care until relapse or programme end as well as cost per week of follow-up were computed. Comparisons were carried out between the groups with or without relapse at the end of the programme. Results: Of the 209 men and 272 women included, 347 patients (72%) finished the programme. Among them, 240 patients (70%) succeeded in quitting and 107 patients (30%) relapsed. As compared with the group relapsing by the end of the programme, the group succeeding in quitting was more often living in a couple (68% vs. 55%, p = 0.029). Their mean weekly costs of visits were higher (CHF 81.2 ± 6.1 vs. 78.4 ± 7.6, p = 0.001), while their mean weekly costs for NRT were similar (CHF 24.2 ± 12.6 vs. 25.4 ± 15.9, p = 0.711). Mean total costs per week were similar (CHF 105.4 ± 15.4 vs. 103.8 ± 19.4, p = 0.252). More intensive NRT at week 4 increased the probability not to relapse at the end of the programme. Conclusions: Over 9 weeks, medical and pharmacological costs of stopping smoking are low. Good medical and social support as well as adequate NRT seem to play a role in successful quitting.