Hippocampal sleep spindles preceding neocortical sleep onset in humans.

The coexistence of regionally dissociated brain activity patterns -with some brain areas being active while other already showing sleep signs- may occur throughout all vigilance states including the transition from wakefulness to sleep and may account for both physiological as well as pathological events. These dissociated electrophysiological states are often characterized by multi-domain cognitive and behavioral impairment such as amnesia for events immediately preceding sleep. By performing simultaneous intracerebral electroencephalographic recordings from hippocampal as well as from distributed neocortical sites in neurosurgical patients, we observed that sleep spindles consistently occurred in the hippocampus several minutes before sleep onset. In addition, hippocampal spindle detections consistently preceded neocortical events, with increasing delays along the cortical antero-posterior axis. Our results support the notion that wakefulness and sleep are not mutually exclusive states, but rather part of a continuum resulting from the complex interaction between diffuse neuromodulatory systems and intrinsic properties of the different thalamocortical modules. This interaction may account for the occurrence of dissociated activity across different brain structures characterizing both physiological and pathological conditions.

History of allergy is a predictor of adverse events in unstable angina treated with coronary angioplasty.

BACKGROUND: The aim was to investigate prognostic relevance of history of allergy in subjects with unstable angina treated with coronary angioplasty. METHODS: Fifty-seven consecutive patients with unstable angina who underwent coronary angioplasty were enrolled in the study and were divided into two groups: those with a history of allergy (Group A, N = 15); and controls (Group C, N =42). Major adverse cardiac events were recorded over a six-month follow-up period. Patients with primary or unsuccessful angioplasty and patients treated with drug eluting stent were excluded from the study. RESULTS: Group A patients (history of allergy) showed a 46.67% incidence of major adverse cardiac events at six-month follow-up (vs. 9.52% Group C, p < 0.01): results remained significant even in a multiple Cox regression analysis (hazard ratio 7.17, 95% CI 1.71-29.98, p < 0.01). CONCLUSION: History of allergy is an independent predictor of major adverse cardiac events after coronary angioplasty in a six-month follow-up period in unstable angina.

A specific deficit in spatial memory acquisition in post-traumatic stress disorder and the role of sleep in its consolidation.

Posttraumatic stress disorder (PTSD) is characterized by the presence of anatomo-functional hippocampal alterations. To date, the ability to orient within the environment, which relies on hippocampal integrity, has never been investigated in PTSD. We hypothesized that the ability to form a cognitive map of the environment would be impaired in PTSD. Moreover, spatial memory consolidation benefits from postlearning sleep. Because PTSD individuals often complain about sleep disturbances, we hypothesized that any sleep effect on memory performance would be hampered in these subjects. Twenty-two subjects, all survivors of the L'Aquila 2009 earthquake, were divided into a PTSD and a control group, based on clinical evaluation. After an acquisition phase, they were tested twice ("test" and "retest") on a virtual navigation task. In addition, participants were administered the Digit Span and Task Switching. Subjective sleep quality and sleep disturbances were also assessed. The two testing sessions were on consecutive mornings, interspersed with a night of sleep. During the acquisition phase, the PTSD group took more than twice as long to form a cognitive map of the environment compared to the control group. However, once this phase was successfully completed, the two groups did not differ at test, but they tendentially differed at postsleep retest. Additional analyses comparing performances between groups on test-retest difference scores confirm that sleep-dependent consolidation may be differentially affected in the two groups. Our findings are strictly confined to the navigation performance, excluding a generalized cognitive deficit. PTSD also reported more subjective sleep disturbances and shorter sleep time than controls, which were correlated to worse performance at retest. The specific deficit in the formation of a cognitive map reported in PTSD may be related to hippocampal dysfunctions as well as to the sleep disturbances experienced by these patients. The possible deficiency of sleep-dependent spatial performance improvement should however be confirmed by further studies comprising a wake control group.

An innovative biofilter technology for reducing environmental spreading of emerging pollutants and odour emissions during municipal sewage treatment.

Wastewater treatment plants (WWTPs) are known sources of contaminants of emerging concern (CECs) spreading into the environment, as well as, of unpleasant odors. CECs represent a potential hazard for human health and the environment being pharmaceutical or biologically active compounds and they are acquiring relevance in European directives. Similarly, the public concern about odour emissions from WWTPs is also increasing due to the decreasing distance between WWTP and residential areas. This study focuses on the effectiveness of the recently developed MULESL technology (MUch LEss SLudge; WO2019097463) in removing CECs and limiting odour emissions from WWTPs. MULESL technology has been developed for its ability to reduce up to 80% the sludge production from WWTPs. However, it is ought to evaluate if the benefits coming from sludge production reduction do not invalidate CECs removal or negatively affect odour emissions. Thus, the performances of a MULESL and a conventional WWTP (flow rate of 375 m3/d and 3600 m3/d, respectively) were compared while treating the same municipal sewage. Whereas both plants succeeded in removing the traditional gross parameters characterizing wastewaters (e.g. chemical oxygen demand, nitrogen), the MULESL was much more effective than the conventional one in terms of CECs removal for about 60% of the identified compounds showing, however, the same or lower effectiveness for about 30% and 10% of them, respectively. This result was attributed to the high sludge retention time and biomass concentration in the MULESL (enabling enrichment of slow growing microorganisms and forcing biomass to use unusual substrates, respectively), and to the biomass feature to grow in the form of biofilm and granules (favoring micropollutants absorption on biomass). Furthermore, odour impact analysis has shown that the MULESL was characterized by a much lower impact, i.e. 45% lower than that of primary and secondary treatments of the conventional WWTP.

Immune response to cytolethal distending toxin of Aggregatibacter actinomycetemcomitans in periodontitis patients.

BACKGROUND AND OBJECTIVE: Cytolethal distending toxin (CDT) is a genotoxin produced by Aggregatibacter actinomycetemcomitans. In spite of its association with pathogenesis, little is known about the humoral immune response against the CDT. This study aimed to test whether subgingival colonization and humoral response to A. actinomycetemcomitans would lead to a response against CDT. MATERIAL AND METHODS: Sera from periodontally healthy, localized and generalized aggressive periodontitis and chronic periodontitis subjects (n = 80) were assessed for immunoglobulin G titers to A. actinomycetemcomitans serotypes a/b/c and to each CDT subunit (CdtA, CdtB and CdtC) by ELISA. A. actinomycetemcomitans subgingival levels and neutralization of CDT activity were also analyzed. RESULTS: Sera from 75.0% localized and 81.8% generalized aggressive periodontitis patients reacted to A. actinomycetemcomitans. A response to serotype b was detected in localized (66.7%) and generalized aggressive periodontitis (54.5%). Reactivity to A. actinomycetemcomitans correlated with subgingival colonization (R = 0.75, p < 0.05). There was no correlation between A. actinomycetemcomitans colonization or response to serotypes and the immunoglobulin G response to CDT subunits. Titers of immunoglobulin G to CdtA and CdtB did not differ among groups; however, sera of all generalized aggressive periodontitis patients reacted to CdtC. Neutralization of CDT was not correlated with levels of antibodies to CDT subunits. CONCLUSION: Response to CdtA and CdtB did not correlate with the periodontal status of the subject in the context of an A. actinomycetemcomitans infection. However, a response to CdtC was found in sera of generalized but not of localized aggressive periodontitis subjects. Differences in response to CdtC between generalized and localized aggressive periodontitis subjects indicate that CDT could be expressed differently by the infecting strains. Alternatively, the antibody response to CdtC could require the colonization of multiple sites.

Sleep electroencephalography and brain maturation: developmental trajectories and the relation with cognitive functioning.

Sleep has a crucial role in brain functioning and cognition, and several sleep electroencephalography (EEG) hallmarks are associated with intellectual abilities, neural plasticity, and learning processes. Starting from this evidence, a growing interest has been raised regarding the involvement of the sleep EEG in brain maturation and cognitive functioning during typical development (TD). The aim of this review is to provide a general framework about the maturational changes and the functional role of the human sleep EEG during TD from birth to late adolescence (≤22 years). The reviewed findings show large developmental modifications in several sleep EEG hallmarks (slow wave activity, sleep spindles, theta activity, and cyclic alternating pattern) during TD, and many studies support the notion of an active role of sleep slow wave activity in supporting brain maturation. Moreover, we focus on the possible relation between sleep microstructure, intelligence, and several memory domains (declarative, emotional, procedural), showing that sleep EEG oscillations seem involved in intellectual abilities and learning processes during TD, although results are often conflicting and divergent from findings in adults. Starting from the present literature, we propose that larger methodological uniformity, greater attention to the topographical and maturational aspects of the sleep EEG oscillations and their mutual interactions, and a higher number of longitudinal studies will be essential to clarify the role of the sleep EEG in cognitive functioning during TD.

Infodemiological patterns in searching medication errors: relationship with risk management and shift work.

INTRODUCTION: Western world health care systems have been trying to improve their efficiency and effectiveness in order to respond properly to population aging and non-communicable diseases epidemic. Treatment of the elderly population is becoming complex due to the high number of prescribed drugs because of multimorbidity. Errors in drugs administration in different health care related settings are an actual important issue due to different causes. Aim of this observational study is to measure the online interest in seeking medication errors information related to risk management and shift work. MATERIALS AND METHODS: We investigated Google Trends® for popular search relating to medication errors, risk management and shift work. Relative search volumes (RSVs) were evaluated from 2008 to 2018. A comparison between RSV curves related to medication errors, risk management and shift work was carried out. Then, we compared the world to Italian search. RESULTS: RSVs were persistently higher for risk management than for medication errors (mean RSVs 069 vs. 48%) and RSVs were stably higher for medication errors than shift work (mean RSVs 48 vs. 22%). In Italy, RSVs were much lower compared to the rest of the world, and RSVs for medication errors during the study period were negligible. Mean RSVs for risk management and shift work were 3 and 25%, respectively. RSVs related to medication errors and clinical risk management were correlated (r=0.520, p<0.0001). CONCLUSIONS: Google Trends® search query volumes related to medication errors, risk management and shift work are different. RSVs for risk management are higher, and they are correlated with medication errors. Also, shift work search appears to be lower. These results should be interpreted in order to correctly evaluate how to decrease the number of medication errors in different health care related setting.

Psychomotor performance is not influenced by brief repeated exposures to mobile phones.

The present study investigated the presence of a cumulative effect of brief and repeated exposures to a GSM mobile phone (902.40 MHz, 217 Hz modulated; peak power of 2 W; average power of 0.25 W; SAR = 0.5 W/kg) on psychomotor functions. To this end, after each of 3 15-min exposures, both an acoustic simple reaction time task (SRTT) and a sequential finger tapping task (SFTT) were administered to 24 subjects. The present study was unable to detect the cumulative effects of brief and repeated EMF exposure on human psychomotor performance, although there was a non-statistical trend to shorter reaction times. In summary, these data show an absence of effects with these particular exposure conditions; however, possible cognitive effects induced by different signal characteristics cannot be excluded.

Electrical stimulation of the frontal cortex enhances slow-frequency EEG activity and sleepiness.

Our aim was to enhance the spontaneous slow-frequency EEG activity during the resting state using oscillating transcranial direct currents (tDCS) with a stimulation frequency that resembles the spontaneous oscillations of sleep onset. Accordingly, in this preliminary study, we assessed EEG after-effects of a frontal oscillatory tDCS with different frequency (0.8 vs. 5 Hz) and polarity (anodal, cathodal, and sham). Two single-blind experiments compared the after effects on the resting EEG of oscillatory tDCS [Exp. 1=0.8 Hz, 10 subjects (26.2 ± 2.5 years); Exp. 2=5 Hz, 10 subjects (27.4 ± 2.4 years)] by manipulating its polarity. EEG signals recorded (28 scalp derivations) before and after stimulation [slow oscillations (0.5-1 Hz), delta (1-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta 1 (13-15 Hz) and beta 2 (16-24 Hz)] were compared between conditions as a function of polarity (anodal vs. cathodal vs. sham) and frequency of stimulation (0.8 vs. 5 Hz). We found a significant relative enhancement of the delta activity after the anodal tDCS at 5 Hz compared to that at 0.8 Hz. This increase, even though not reaching the statistical significance compared to sham, is concomitant to a significant increase of subjective sleepiness, as assessed by a visual analog scale. These two phenomena are linearly related with a regional specificity, correlations being restricted to cortical areas perifocal to the stimulation site. We have shown that a frontal oscillating anodal tDCS at 5 Hz results in an effective change of both subjective sleepiness and spontaneous slow-frequency EEG activity. These changes are critically associated to both stimulation polarity (anodal) and frequency (5 Hz). However, evidence of frequency-dependence seems more unequivocal than evidence of polarity-dependence.

Is the brain influenced by a phone call? An EEG study of resting wakefulness.

We recorded the resting electroencephalogram of 20 healthy subjects in order to investigate the effect of electromagnetic field (EMF) exposure on EEG waking activity and its temporal development. The subjects were randomly assigned to two groups and exposed, in double-blind conditions, to a typical mobile phone signal (902.40 MHz, modulated at 217 Hz, with an average power of 0.25 W) before or during the EEG recording session. The results show that, under real exposure as compared to baseline and sham conditions, EEG spectral power was influenced in some bins of the alpha band. This effect was greater when the EMF was on during the EEG recording session than before it. The present data lend further support to the idea that pulsed high-frequency electromagnetic fields can affect normal brain functioning, also if no conclusions can be drawn about the possible health effects.

Reflective lateral eye movements: individual styles, cognitive and lateralization effects.

The direction of gaze shifts following verbal and spatial questions was recorded by direct observation in two separate sessions in 80 right-handed Ss. Ocular events were stable over the sessions, and some Ss were classified reliably as lateral, vertical or bidirectional eye movers. No effect for type of question was found in lateral direction either in the general sample or in the bidirectional sample. Verbal questions elicited more downward movements than spatial questions. Less eye movements were found for spatial and for easy questions. These findings suggest a link between ocular motility and cognition independent of the lateralization issue.

Which hemisphere falls asleep first?

Behavioral tasks (reaction times to acoustic stimuli and finger tapping tasks) performed by normal subjects when sleepy or attempting to fall asleep have been used as indices of hemispheric asymmetries during the sleep onset period. Results show a stronger impairment of the left hemisphere (right hand) both in reacting to external stimuli and in sustaining endogenous motor programs. The left hemisphere seems to fall asleep earlier than the right hemisphere.

Prevalent direction of reflective lateral eye movements and ear asymmetries in a dichotic test of musical chords.

Subjects who consistently move their gaze either to the right or to the left while reflecting on visuo-spatial or verbal questions are usually called "lateral eye movers". This study evaluated auditory asymmetries to a dichotic test of musical chords in 23 right-handed females, selected through test-retest as reliable lateral eye movers; 12 were "left movers" (LMs) and 11 were "right movers" (RMs). During the assessment of the prevalent direction of gaze as well as during the dichotic test, the oculomotor activity was controlled through a video camera. The hypothesis was that the left ear advantage usually found with dichotic chords is enhanced in LMs and reduced in RMs, and that this effect is not due to the facilitating influence of lateral eye movements occurring during the task. Results show that: (a) left movers exhibit a marked advantage of the left ear while right movers do not exhibit any significant ear advantage; (b) despite the instruction to fix a central point, lateral movers tend to show unwarranted eye movements in their usual direction; (c) the effect of the prevalent direction of gaze on the dichotic advantage is not due to eye movements made during the dichotic test. These findings give further support to the hypothesis that the tendency to consistently shift the gaze to one side is related to hemispheric asymmetries as measured by lateralized tests.

The boundary between wakefulness and sleep: quantitative electroencephalographic changes during the sleep onset period.

Microstructural electroencephalographic changes during the wakefulness-sleep transition have been investigated by comparing two definitions of sleep onset: the first occurrence of stage 1 and of stage 2. Power values were calculated across a 1-28-Hz frequency range in a 1-Hz bin resolution in the sleep recordings of 26 normal subjects. Quantitative changes were assessed after averaging individual time series, aligned with respect to the first occurrence of stage 1 or of stage 2. The time course of the single-Hz activity revealed a linear increase of power in the 1-6-Hz range and a linear decrease in the 9-12- and 16-28-Hz ranges during the stage 1 transition. During the stage 2 transition, electroencephalogram power linearly increased in the 1-7- and 14-15-Hz ranges and decreased in the 18-28-Hz range, while the 8-12-Hz range fitted a second-order polynomial curve. The two 'switch' points were also compared in their ability to differentiate Hz by Hz wakefulness from sleep: a lower mean power was found after stage 1 onset in the 9-11-Hz and 20-28-Hz bins and a higher one in the 1-5-Hz bins, while a higher power was found in the 1-8-Hz and 12-16-Hz bins and a lower one in 18-28-Hz bins after stage 2 onset. The time course of three electroencephalographic frequency ranges [delta/theta/sigma (1-7 and 12-16 Hz); beta (17-28 Hz); alpha (8-11 Hz)], grouped on the basis of a principal component analysis, fitted a first-order polynomial curve for the first two ranges, and a second-order polynomial curve for the last, with a progressive decrease during wakefulness, a minimum point during stage 1, and a subsequent increase during stage 2. The uniformly increasing electroencephalographic power across the 1-16-Hz frequency range during stage 2 and the shift of functional meaning for the alpha power during stage 1 point to the start of stage 2 as a more reliable boundary between wakefulness and sleep.

Sleep deprivation and phasic activity of REM sleep: independence of middle-ear muscle activity from rapid eye movements.

In the recovery nights after total and partial sleep deprivation there is a reduction of rapid eye movements during REM sleep as compared to baseline nights; recent evidence provided by a selective SWS deprivation study also shows that the highest percentage of variance of this reduction is explained by SWS rebound. The present study assesses whether the reduction of rapid eye movements (REMs) during the recovery night after total sleep deprivation is paralleled by a decrease of middle-ear muscle activity (MEMA), another phasic muscle activity of REM sleep. Standard polysomnography, MEMA and REMs of nine subjects were recorded for three nights (one adaptation, one baseline, one recovery); baseline and recovery night were separated by a period of 40 hours of continuous wake. Results show that, in the recovery night, sleep deprivation was effective in determining an increase of SWS amount and of the sleep efficiency index, and a decrease of stage 1, stage 2, intra-sleep wake, and NREM latencies, without affecting REM duration and latency. However, MEMA frequency during REM sleep did not diminish during these nights as compared to baseline ones, while there was a clear effect of REM frequency reduction. Results indicate an independence of phasic events of REM sleep, suggesting that the inverse relation between recovery sleep after sleep deprivation and REM frequency is not paralleled by a concomitant variation in MEMA frequency.

EEG arousals in normal sleep: variations induced by total and selective slow-wave sleep deprivation.

STUDY OBJECTIVES: Aim of the present study was to assess changes in arousal rates after selective slow-wave (SWS) and total sleep deprivations. DESIGN: Two-way mixed design comparing the arousal index (Al), as expressed by the number of EEG arousals divided by sleep duration, in totally or selectively sleep deprived subjects. SETTING: Sleep laboratory. PATIENTS OR PARTICIPANTS: Nineteen normal male subjects [mean age=23.3 years (S.E.M.=0.55)]. INTERVENTIONS: Al was measured in baseline nights and after selective SWS (N=10) and total sleep deprivation (N=9). MEASUREMENTS AND RESULTS: During the baseline nights AI values changed across sleep stages as follows: stage 1 > stage 2 and REM > SWS, but did not present any significant variations as a function of time elapsed from sleep onset. The recovery after deprivation showed a reduction in EEG arousals, more pronounced after total sleep deprivation; this decrease affected NREM but not REM sleep. During the baseline nights Al showed a close-to-significance negative correlation with REM duration, while during the recovery nights a significant positive relation with stage 1 duration was found. CONCLUSIONS: The present results suggest that recuperative processes after sleep deprivation are also associated with a higher sleep continuity as defined by the reduction of EEG arousals.

A finger-tapping task and a reaction time task as behavioral measures of the transition from wakefulness to sleep: which task interferes less with the sleep onset process.

The aim of this study was to assess whether a finger-tapping task (FTT), in which normal subjects repeatedly tap on a button while falling asleep, could be less disturbing and provide comparable information on the sleep onset period (SOP) with respect to a reaction-time task (RTT) to acoustic stimuli, in which the onset of sleep can be delayed by the arousing effect of the acoustic stimuli. Twelve subjects slept at their homes and six slept in a sleep laboratory for four consecutive nights. After one adaptation night and one baseline night, subjects were required to fall asleep in the third and fourth nights, bimanually performing either a RTT or a FTT. The results indicate that the FTT interfaces less with the SOP compared to the RTT and suggest that the FTT provides further advantages as a behavioral measure of the transition from wakefulness to sleep. In fact, the tapping task is associated with significantly shorter behavioral and polysomnographic sleep onset latencies and with a greater proportion of slow-wave sleep (SWS) during the transition from wakefulness to sleep compared with the RTT. Furthermore, correlations among subjective, behavioral, and electroencephalograph (EEG) latencies confirm the validity of the finger-tapping task as a behavioral measure of sleep onset.

Time-course of electromagnetic field effects on human performance and tympanic temperature.

The study aimed to investigate the time-course of electromagnetic field (EMF)-induced effects on human cognitive and behavioral performance and on tympanic temperature. Subjects were randomly assigned to two groups, exposed to a 902.40 MHz EMF before the testing session, or to the same signal during the data collecting session. Following a double-blind paradigm, subjects were tested on four performance tasks: an acoustic simple-reaction time task, a visual search task, an arithmetic descending subtraction task and an acoustic choice-reaction time task. Moreover, tympanic temperature was collected five times during each session. Results indicated an improvement of both simple- and choice-reaction times and an increase of local temperature on the exposed region under the active exposure. There was a clear time-course of the reaction time and temperature data, indicating that performance and physiological measures need a minimum of 25 min of EMF exposure to show appreciable changes.

Effect of slow-wave sleep deprivation on topographical distribution of spindles.

Spindle activity, visually scored in the 12-15 Hz range over antero-posterior midline derivations, has been assessed in ten normal subjects during a baseline and a recovery sleep after 2 nights of selective slow-wave sleep (SWS) deprivation. The recovery sleep, characterized by a significant increase of stage 4 and SWS as compared to the baseline, revealed that sleep spindles are reduced in the first NREM sleep cycle. The size of this reduction in spindle density progressively decreased in the course of the night, paralleling the depletion of SWS rebound. Topographical distribution of spindle activity showed a global linear increase over consecutive NREM-REM sleep cycles, regarding to the whole antero-posterior midline EEG derivations except the occipital one. It is concluded that the SWS rebound after 2 nights of selective SWS deprivation is associated with a reduction of spindles during stage 2.

Auditory arousal thresholds after selective slow-wave sleep deprivation.

OBJECTIVES: The aim of this study is to assess Auditory Arousal Thresholds (AATs) three times during an undisturbed baseline night and to compare them to AATs during the recovery night that follows two consecutive nights of selective SWS deprivation. The presence of a time-of-night effect on AATs will also be assessed. METHODS: Ten male Ss slept in the laboratory for 6 consecutive nights. The first two nights were undisturbed. The 3rd night was considered as baseline. During the 4th and 5th nights, selective SWS deprivation was obtained by means of acoustic stimulation. The 6th night was a recovery. In the last 4 nights Ss were awakened three times, after 2, 5 and 7.5 h of sleep, respectively. All the awakenings were carried out from stage 2 (after at least 5 consecutive min of stage 2), by means of 1000 Hz ascending tone series. The AAT determination was based on EEG-EMG criteria: at least 10-s of clear alpha rhythm and/or a 10 s movement arousal. RESULTS: During both deprivation nights, SWS amount was close to zero. In the ensuing recovery night a significant SWS rebound was found, accompanied by a significant increase of AATs with respect to the baseline. Furthermore, there was a significant linear decrease of AATs during the night. Finally, the individual correlations between AATs and SWS amount were significant in 4 out of 10 Ss. CONCLUSIONS: These results confirm that AATs are a reliable index of sleep depth by showing that the SWS rebound following selective SWS deprivation is paralleled by a significant AAT enhancement. The experimental paradigm also allows us to claim that AATs show a decreasing linear trend during the night, having excluded any procedural bias. Finally, AATs can be directly related to SWS amount that preceded the awakening, although the individual correlations between AATs and SWS have to be considered with caution, given the high inter-subject variability and the small number of observations.