We have studied the mechanisms of auditory hair cell death after insults in vitro and in vivo. We show DNA fragmentation of hair cell nuclei after ototoxic drug and intense noise trauma. By using phospho-specific c-Jun-N-terminal kinase (JNK) and c-Jun antibodies in immunohistochemistry, we show that the JNK pathway, associated with stress, injury, and apoptosis, is activated in hair cells after trauma. CEP-1347, a derivative of the indolocarbazole K252a, is a small molecule that has been shown to attenuate neurodegeneration by blocking the activation of JNK (). Subcutaneously delivered CEP-1347 attenuated noise-induced hearing loss. The protective effect was demonstrated by functional tests, which showed less hearing threshold shift in CEP-1347-treated than in nontreated guinea pigs, and by morphometric methods showing less hair cell death in CEP-1347-treated cochleas. In organotypic cochlear cultures, CEP-1347 prevented neomycin-induced hair cell death. In addition to hair cells, CEP-1347 promoted survival of dissociated cochlear neurons. These results suggest that therapeutic intervention in the JNK signaling cascade, possibly by using CEP-1347, may offer opportunities to treat inner ear injuries.

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Introduction:Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves.Aims:Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use.Methods:Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented.Results:Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p < .001). When overnight improvement of memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality.Conclusions:We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future.

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SUMMAR Y Sleep in shift work has been studied extensively in regular shift systems but to a lesser degree in irregular shifts. Our main aim was to examine the sleep-wake rhythm in shift combinations ending with the night or the morning shift in two irregular shift systems. Three weeks' sleep ⁄ work shift diary data, collected from 126 randomly selected train drivers and 104 traffic controllers, were used in statistical analyses including a linear mixed model and a generalized linear model for repeated measurements. The results showed that the sleep-wake rhythm was significantly affected by the shift combinations. The main sleep period before the first night shift shortened by about 2 h when the morning shift immediately preceded the night shift as compared with the combination containing at least 36 h of free time before the night shift (reference combination). The main sleep period before the night shift was most curtailed between two night shifts, on average by 2.9 and 3.5 h among the drivers and the controllers, respectively, as compared with the reference combination. Afternoon napping increased when the morning or the day shift immediately preceded the night shift, the odds being 4.35-4.84 in comparison with the reference combination. The main sleep period before the morning shift became 0.5 h shorter when the evening shift preceded the morning shift in comparison with the sleep period after a free day. The risk for dozing off during the shift was associated only with the shift length, increasing by 17 and 35% for each working hour in the morning and the night shift, respectively. The results demonstrate advantageous and disadvantageous shift combinations in relation to sleep and make it possible to improve the ergonomy of irregular shift systems.

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It has been shown in previous studies on sleep electroencephalogram (EEG) that spindles are slower in the beginning of the night fastening towards the end of the night. Corresponding findings have been obtained by spectral analysis. The present study was based on our preliminary observation that slower spindles are found in the middle of the nonrapid eye movement (NREM) sleep episodes as compared with the beginning or the end of the episodes. Eight healthy female and six male subjects were studied. Sleep spindles were visually selected and spindle frequencies calculated for 11 analysis points in each NREM sleep episode. The median spindle frequencies formed a clear U‐shape within NREM sleep episodes with an initial decrease and final increase. The decrease was statistically significant within the first four NREM sleep episodes. It is possible that the spindle frequency pattern could be used to reveal variations in sleep depth within sleep stage 2. In animal studies the spindle frequency has been found to be associated to the duration of the hyperpolarization‐rebound sequences of the thalamocortical cells. If it is assumed that the same cellular mechanisms are responsible for spindle frequencies in humans then the study of variations in spindle frequency could be used to examine the NREM sleep process in humans.

PurposeAlthough shift work disorder (SWD) affects a major part of the shift working population, little is known about its manifestation in real life. This observational field study aimed to provide a detailed picture of sleep and alertness among shift workers with a questionnaire-based SWD, by comparing them to shift workers without SWD during work shifts and free time.MethodsSWD was determined by a questionnaire. Questionnaires and 3-week field monitoring, including sleep diaries, actigraphy, the Karolinska Sleepiness Scale (KSS), EEG-based sleep recordings, and Psychomotor Vigilance Tasks (PVT), were used to study 22 SWD cases and 9 non-SWD workers.ResultsThe SWD group had a shorter subjective total sleep time and greater sleep debt before morning shifts than the non-SWD group. Unlike the non-SWD group, the SWD group showed little compensatory sleep on days off. The SWD group had lower objective sleep efficiency and longer sleep latency on most days, and reported poorer relaxation at bedtime and sleep quality across all days than the non-SWD group. The SWD group’s average KSS-sleepiness was higher than the non-SWD group’s sleepiness at the beginning and end of morning shifts and at the end of night shifts. The SWD group also had more lapses in PVT at the beginning of night shifts than the non-SWD group.ConclusionsThe results indicate that SWD is related to disturbed sleep and alertness in association with both morning and night shifts, and to less compensatory sleep on days off. SWD seems to particularly associate with the quality of sleep.Electronic supplementary materialThe online version of this article (10.1007/s00420-018-1386-4) contains supplementary material, which is available to authorized users.