HokB Monomerization and Membrane Repolarization Control Persister Awakening.

Every bacterial population harbors a small subpopulation of so-called persisters that are transiently antibiotic tolerant. These persisters are associated with the recalcitrance of chronic infections because they can recolonize the host after antibiotic removal. Although several effectors have been described to induce persistence, persister cell awakening is poorly understood. We previously reported that the toxin HokB induces persistence via pore formation, resulting in membrane depolarization and ATP leakage. We now delineate mechanisms responsible for the awakening of HokB-induced persisters. We show that HokB dimerization by the oxidoreductase DsbA is essential for pore formation and peptide stability. Pores are disassembled via DsbC-mediated monomerization, which targets HokB for DegQ-mediated degradation. Finally, pore disassembly allows membrane repolarization by the electron transport chain, supporting cells to resume growth. These results provide a detailed view of both the formation and awakening of HokB-induced persister cells.

Biomathematical modeling of fatigue due to sleep inertia.

Biomathematical models of fatigue capture the physiology of sleep/wake regulation and circadian rhythmicity to predict changes in neurobehavioral functioning over time. We used a biomathematical model of fatigue linked to the adenosinergic neuromodulator/receptor system in the brain as a framework to predict sleep inertia, that is, the transient neurobehavioral impairment experienced immediately after awakening. Based on evidence of an adenosinergic basis for sleep inertia, we expanded the biomathematical model with novel differential equations to predict the propensity for sleep inertia during sleep and its manifestation after awakening. Using datasets from large laboratory studies of sleep loss and circadian misalignment, we calibrated the model by fitting just two new parameters and then validated the model's predictions against independent data. The expanded model was found to predict the magnitude and time course of sleep inertia with generally high accuracy. Analysis of the model's dynamics revealed a bifurcation in the predicted manifestation of sleep inertia in sustained sleep restriction paradigms, which reflects the observed escalation of the magnitude of sleep inertia in scenarios with sleep restriction to less than âˆ¼ 4 h per day. Another emergent property of the model involves a rapid increase in the predicted propensity for sleep inertia in the early part of sleep followed by a gradual decline in the later part of the sleep period, which matches what would be expected based on the adenosinergic regulation of non-rapid eye movement (NREM) sleep and its known influence on sleep inertia. These dynamic behaviors provide confidence in the validity of our approach and underscore the predictive potential of the model. The expanded model provides a useful tool for predicting sleep inertia and managing impairment in 24/7 settings where people may need to perform critical tasks immediately after awakening, such as on-demand operations in safety and security, emergency response, and health care.

Consciousness in non-REM-parasomnia episodes.

Sleepwalking and related parasomnias are thought to result from incomplete awakenings out of non-rapid eye movement (non-REM) sleep. Non-REM parasomnia behaviours have been described as unconscious and automatic, or related to vivid, dream-like conscious experiences. Similarly, some observations have suggested that patients are unresponsive during episodes, while others that they can interact with their surroundings. To better grasp and characterise the full spectrum of consciousness and environmental (dis)connection associated with behavioural episodes, 35 adult patients with non-REM sleep parasomnias were interviewed in-depth about their experiences. The level of consciousness during parasomnia episodes was reported to be variable both within and between individuals, ranging from minimal or absent consciousness and largely automatic behaviours (frequently/always present in 36% of patients) to preserved conscious experiences characterised by delusional thinking to varying degrees of specificity (65%), often about impending danger, variably formed, uni- or multisensory hallucinations (53%), impaired insight (77%), negative emotions (75%), and variable, but often pronounced, amnesia (30%). Patients described their experiences as a dream scene during which they felt awake ("awake dreaming"). The surroundings were either realistically perceived, misinterpreted (in the form of perceptual illusions or misidentifications of people), or entirely hallucinated as a function of the prevailing delusion. These observations suggest that the level of consciousness, amnesia and sensory disconnection during non-REM parasomnia episodes is variable and graded. In their full-fledged expression, non-REM parasomnia experiences feature several core features of dreams. They therefore represent a valuable model for the study of consciousness, sleep-related sensory disconnection and dreaming.

Volatile versus propofol sedation after cardiac valve surgery: a single-center prospective randomized controlled trial.

BACKGROUND: Optimal intensive care of patients undergoing valve surgery is a complex balancing act between sedation for monitoring and timely postoperative awakening. It remains unclear, if these requirements can be fulfilled by volatile sedations in intensive care medicine in an efficient manner. Therefore, this study aimed to assess the time to extubation and secondary the workload required. METHODS: We conducted a prospective randomized single-center trial at a tertiary university hospital to evaluate the postoperative management of open valve surgery patients. The study was randomized with regard to the use of volatile sedation compared to propofol sedation. Sedation was discontinued 60 min after admission for critical postoperative monitoring. RESULTS: We observed a significantly earlier extubation (91 ± 39 min vs. 167 ± 77 min; p < 0.001), eye-opening (86 ± 28 min vs. 151 ± 71 min; p < 0.001) and command compliance (93 ± 38 min vs. 164 ± 75 min; p < 0.001) using volatile sedation, which in turn was associated with a significantly increased workload of a median of 9:56 min (± 4:16 min) set-up time. We did not observe any differences in complications. Cardiopulmonary bypass time did not differ between the groups 101 (IQR 81; 113) versus 112 (IQR 79; 136) minutes p = 0.36. CONCLUSIONS: Using volatile sedation is associated with few minutes additional workload in assembling and enables a significantly accelerated evaluation of vulnerable patient groups. Volatile sedation has considerable advantages and emerges as a safe sedation technique in our vulnerable study population. TRIAL REGISTRATION: Clinical trials registration (NCT04958668) was completed on 1 July 2021.

Relationship between insomnia and pain in patients with chronic orofacial pain.

OBJECTIVE: Few studies have investigated specific associations between insomnia and orofacial pain (OFP). The aim of this cross-sectional study was to examine relationships of insomnia with pain, mental health, and physical health variables among treatment-seeking patients with chronic OFP. METHODS: OFP diagnosis, demographics, insomnia symptoms, pain intensity, interference, and duration, mental health measures, and number of medical comorbidities were extracted from the medical records of 450 patients receiving an initial appointment at a university-affiliated tertiary OFP clinic. T-tests compared differences between patients with and without insomnia symptomatology, and between patients with different insomnia subtypes (delayed onset/early wakening). RESULTS: Compared to patients without insomnia, those with elevated insomnia symptomatology (45.1%) reported higher pain intensity (60.70 ± 20.61 vs 44.15 ± 21.69; P < .001) and interference (43.81 ± 29.84 vs 18.40 ± 23.43; P < 0.001), depression/anxiety symptomatology (5.53 ± 3.32 vs 2.72 ± 2.66; P < 0.001), dissatisfaction with life (21.63 ± 6.95 vs 26.50 ± 6.21; P < .001), and number of medical comorbidities (6.72 ± 5.37 vs 4.37 ± 4.60; P < .001). Patients with Sleep Onset Latency insomnia (SOL-insomnia) (N = 76) reported higher pain intensity (t = 3.57; P < 0.001), and pain interference (t = 4.46; P < .001) compared to those without SOL-insomnia. Those with Early Morning Awakening insomnia (EMA-insomnia) (N = 71) did not significantly differ from those without EMA-insomnia on any of the variables. Differences remained significant after adjusting for age, sex, primary OFP diagnosis, and pain intensity. CONCLUSIONS: Insomnia is associated with pain outcomes and should be appropriately managed when treating patients with chronic OFP.

Outcome prediction in comatose cardiac arrest patients with initial shockable and non-shockable rhythms.

BACKGROUND: Prognosis after out-of-hospital cardiac arrest (OHCA) is presumed poorer in patients with non-shockable than shockable rhythms, frequently leading to treatment withdrawal. Multimodal outcome prediction is recommended 72 h post-arrest in still comatose patients, not considering initial rhythms. We investigated accuracy of outcome predictors in all comatose OHCA survivors, with a particular focus on shockable vs. non-shockable rhythms. METHODS: In this observational NORCAST sub-study, patients still comatose 72 h post-arrest were stratified by shockable vs. non-shockable rhythms for outcome prediction analyzes. Good outcome was defined as cerebral performance category 1-2 within 6 months. False positive rate (FPR) was used for poor and sensitivity for good outcome prediction accuracy. RESULTS: Overall, 72/128 (56%) patients with shockable and 12/50 (24%) with non-shockable rhythms had good outcome (p < .001). For poor outcome prediction, absent pupillary light reflexes (PLR) and corneal reflexes (clinical predictors) 72 h after sedation withdrawal, PLR 96 h post-arrest, and somatosensory evoked potentials (SSEP), all had FPR <0.1% in both groups. Unreactive EEG and neuron-specific enolase (NSE) >60 µg/L 24-72 h post-arrest had better precision in shockable patients. For good outcome, the clinical predictors, SSEP and CT, had 86%-100% sensitivity in both groups. For NSE, sensitivity varied from 22% to 69% 24-72 h post-arrest. The outcome predictors indicated severe brain injury proportionally more often in patients with non-shockable than with shockable rhythms. For all patients, clinical predictors, CT, and SSEP, predicted poor and good outcome with high accuracy. CONCLUSION: Outcome prediction accuracy was comparable for shockable and non-shockable rhythms. PLR and corneal reflexes had best precision 72 h after sedation withdrawal and 96 h post-arrest.

Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis.

Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment experiences to health disparities. In this series of meta-analyses, we aimed to quantify the existing evidence on the effect of child maltreatment on various measures of HPA axis activity. The systematic literature search yielded 1,858 records, of which 87 studies (k = 132) were included. Using random-effects models, we found evidence for blunted cortisol stress reactivity in individuals exposed to child maltreatment. In contrast, no overall differences were found in any of the other HPA axis activity measures (including measures of daily activity, cortisol assessed in the context of pharmacological challenges and cumulative measures of cortisol secretion). The impact of several moderators (e.g., sex, psychopathology, study quality), the role of methodological shortcomings of existing studies, as well as potential directions for future research are discussed.

Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.

BACKGROUND: A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome. METHODS: Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items. RESULTS: In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome. CONCLUSIONS: Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics.

Stress and the hypothalamic-pituitary-adrenal axis: How can the COVID-19 pandemic inform our understanding and treatment of acute insomnia?

Stress and sleep are very closely linked, and stressful life events can trigger acute insomnia. The ongoing COVID-19 pandemic is highly likely to represent one such stressful life event. Indeed, a wide range of cross-sectional studies demonstrate that the pandemic is associated with poor sleep and sleep disturbances. Given the high economic and health burden of insomnia disorder, strategies that can prevent and treat acute insomnia, and also prevent the transition from acute insomnia to insomnia disorder, are necessary. This narrative review outlines why the COVID-19 pandemic is a stressful life event, and why activation of the hypothalamic-pituitary-adrenal axis, as a biological marker of psychological stress, is likely to result in acute insomnia. Further, this review outlines how sleep disturbances might arise as a result of the COVID-19 pandemic, and why simultaneous hypothalamic-pituitary-adrenal axis measurement can inform the pathogenesis of acute insomnia. In particular, we focus on the cortisol awakening response as a marker of hypothalamic-pituitary-adrenal axis function, as cortisol is the end-product of the hypothalamic-pituitary-adrenal axis. From a research perspective, future opportunities include identifying individuals, or particular occupational or societal groups (e.g. frontline health staff), who are at high risk of developing acute insomnia, and intervening. From an acute insomnia treatment perspective, priorities include testing large-scale online behavioural interventions; examining if reducing the impact of stress is effective and, finally, assessing whether "sleep vaccination" can maintain good sleep health by preventing the occurrence of acute insomnia, by preventing the transition from acute insomnia to insomnia disorder.

Circadian aspects in the aetiology and pathophysiology of insomnia.

Because the endogenous circadian pacemaker is a very strong determinant of alertness/sleep propensity across the 24 h period, its mistiming may contribute to symptoms of insomnia (e.g., difficulties initiating sleep and maintaining sleep) and to the development of insomnia disorder. Despite the separation of insomnia and circadian rhythm disorders in diagnostic nosology implying independent pathophysiology, there is considerable evidence of co-morbidity and interaction between them. Sleep onset insomnia is associated with later timed circadian rhythms and can be treated with morning bright light to shift rhythms to an earlier timing. It is also possible that the causal link may go in both directions and that having a delayed circadian rhythm can result in enough experiences of delayed sleep onset to lead to some conditioned insomnia or insomnia disorder further exacerbating a delayed circadian rhythm. Early morning awakening insomnia is associated with an advanced circadian phase (early timing) and can be treated with evening bright light resulting in a delay of rhythms and an improved ability to sleep later in the morning and to obtain more sleep. There is some evidence suggesting that sleep maintenance insomnia is associated with a blunted amplitude of circadian rhythm that may be treated with increased regularity of sleep and light exposure timing. However, this is an insomnia phenotype that requires considerably more circadian research as well as further insomnia clinical research with the other insomnia phenotypes incorporating circadian timing measures and treatments.

Quantitative analysis of early-stage EEG reactivity predicts awakening and recovery of consciousness in patients with severe brain injury.

BACKGROUND: Decisions of withdrawal of life-sustaining therapy for patients with severe brain injury are often based on prognostic evaluations such as analysis of electroencephalography (EEG) reactivity (EEG-R). However, EEG-R usually relies on visual assessment, which requires neurophysiological expertise and is prone to inter-rater variability. We hypothesised that quantitative analysis of EEG-R obtained 3 days after patient admission can identify new markers of subsequent awakening and consciousness recovery. METHODS: In this prospective observational study of patients with severe brain injury requiring mechanical ventilation, quantitative EEG-R was assessed using standard 11-lead EEG with frequency-based (power spectral density) and functional connectivity-based (phase-lag index) analyses. Associations between awakening in the intensive care unit (ICU) and reactivity to auditory and nociceptive stimulations were assessed with logistic regression. Secondary outcomes included in-ICU mortality and 3-month Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Of 116 patients, 86 (74%) awoke in the ICU. Among quantitative EEG-R markers, variation in phase-lag index connectivity in the delta frequency band after noise stimulation was associated with awakening (adjusted odds ratio=0.89, 95% confidence interval: 0.81-0.97, P=0.02 corrected for multiple tests), independently of age, baseline severity, and sedation. This new marker was independently associated with improved 3-month CRS-R (adjusted ß=-0.16, standard error 0.075, P=0.048), but not with mortality (adjusted odds ratio=1.08, 95% CI: 0.99-1.18, P=0.10). CONCLUSIONS: An early-stage quantitative EEG-R marker was independently associated with awakening and 3-month level of consciousness in patients with severe brain injury. This promising marker based on functional connectivity will need external validation before potential integration into a multimodal prognostic model.

Identifying Predictors of Extubation on the day of Passing an SBT in Critically ill Adults.

INTRODUCTION: Many patients who pass a spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT) do not undergo extubation that day. We aimed to identify predictors of extubation on the day of passing an SBT and to develop prediction models for extubation among mechanically ventilated patients. METHODS: In a cohort of mechanically ventilated patients who had passed an SBT in a single, academic medical intensive care unit (ICU) from 2018 to 2019, we developed a logistic regression model for identifying predictors of extubation. RESULTS: Of 745 patients in our study, 77% were extubated the day they passed a SBT. Independent predictors of extubation included higher Richmond Agitation Sedation Scale (RASS) (-2 compared to -4: odds ratio (OR) 1.83, 95% confidence interval (CI) 1.56 to 2.14), receipt of sedation on the day prior (OR 2.12, 95% CI 1.63 to 2.74), absence of diagnosis of sepsis or septic shock (OR 0.77, 95% CI 0.59 to 1), absence of neurological illness (OR 0.59, 95% CI 0.37 to 0.96), indication for intubation of altered mental status, seizure, or agitation (OR 1.67, 95% CI 1.05 to 2.65), and absence of hemodynamic instability or cardiac arrest (OR 0.67, 95% CI 0.47 to 0.95). CONCLUSION AND RELEVANCE: Patients on mechanical ventilation were more likely to be extubated on the day they passed an SBT if they had higher RASS scores, received sedation the day prior, or did not have diagnosis of sepsis, neurological illness, or hemodynamic instability. Future research should attempt to identify and address modifiable risk factors for failure to extubate after passing an SBT.

Comparison of SAT and SBT Conduct During the ABC Trial and PILOT Trial.

BACKGROUND: Implementation of the "B" element-both spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs)-of the ABCDEF bundle improves the outcomes for mechanically ventilated patients. In 2021, the Pragmatic Investigation of optimal Oxygen Targets (PILOT) trial investigating optimal oxygenation targets in patients on mechanical ventilation was completed. OBJECTIVES: To compare SAT and SBT conduct between a randomized controlled trial and current clinical care. METHODS: The 2008 Awakening and Breathing Controlled (ABC) Trial (2003-2006) randomized mechanically ventilated patients to paired SATs and SBTs versus sedation per usual care plus SBTs. The PILOT trial (2018-2021) enrolled patients years later where SAT + SBT conduct was observed. We compared SAT and SBT conduct in ABC's interventional group (SAT + SBT; n = 167, 1140 patient days) to that in PILOT (n = 2083, 8355 patient days). RESULTS: Spontaneous awakening trial safety screens were done in all 1140 ABC patient-days on sedation and/or analgesia and in 3889 of 4228 (92%) in PILOT. Spontaneous awakening trial safety screens were passed in 939 of 1140 (82%) instances in ABC versus only 1897 of 3889 (49%) in PILOT. Interestingly, SAT was performed in ≥95% of passed SAT safety screens in both trials and was passed in 837 of 895 (94%) in ABC versus 1145 of 1867 (61%) in PILOT. SBT safety screens were performed in all 983 ABC instances and 8031 of 8370 (96%) in PILOT. SBT safety screens were passed in 647 of 983 (66%) in ABC versus 4475 of 8031 (56%) in PILOT. Spontaneous breathing trial was performed in ≥93% of passed SBT safety screens in both trials and was passed in 319 of 603 (53%) in ABC versus 3337 of 4454 (75%) in PILOT. CONCLUSION: This study compared SAT/SBT conduction in an ideal setting to real-world practice, 13 years later. Performance of SAT/SBT safety screens, SATs, and SBTs between a definitive clinical trial (ABC) as compared to current clinical care (PILOT) remained high.

The cortisol awakening response and the late positive potentials evoked by unpleasant emotional pictures in healthy adults.

The cortisol awakening response (CAR) refers to a sharp rise in cortisol concentrations within the 45 min following morning awakening. Alterations in CAR have been associated with various internalizing symptoms and brain function. The current study aimed to investigate the association between CAR and neural activity in response to unpleasant emotional pictures. A total of 46 healthy adults (22.55 years ± 1.69) collected saliva samples at 0, 30, and 45 min post-awakening on two days to assess the CAR. In the afternoon after CAR measurement on the first day, electroencephalograms were recorded when the participants completed a passive viewing task. The results showed that a greater CAR was associated with a decreased late positive potential difference score between unpleasant and neutral stimuli. This finding indicates that a larger CAR may be associated with decreased attentional engagement to unpleasant emotional information in healthy adults.

Unique and interactive associations of proactive and reactive aggression with cortisol secretion.

The association between aggressive behaviors and diurnal cortisol levels has been debated over the past two decades, as some studies found a negative link between the two, whereas others reported no or a positive association. One possible explanation for these contradictory results is that past studies failed to distinguish between proactive (PROA) and reactive (REA) aggression. The present study examined the unique and joint associations of PROA and REA with three diurnal cortisol indicators: awakening levels, awakening response, and diurnal change. Participants were 542 youths (55.4% girls) followed longitudinally. Teachers evaluated aggressive behaviors when participants were in Grades 4 and 6. In Grade 8, participants provided four saliva samples (i.e., awakening, 30 min thereafter, late afternoon, and bedtime) on four collection days. Controlling for several confounders, multilevel regression analyses revealed an inverse relation between PROA and the CAR in boys who displayed lower or moderate levels of REA, but not in those who exhibited higher levels of REA. No associations emerged with other cortisol indicators. These results are consistent with reports of lower physiological activity in individuals with PROA and underscore the confounding influence of REA in the association between the CAR and proactive aggression.

Cortisol awakening response and testosterone jointly affect adolescents' theory of mind.

Adolescence is a critical period for the maturation of neurobiological processes and hormone secretion. Recent studies on the dual-hormone hypothesis have indicated that basal cortisol and testosterone jointly affect dominant and aggressive behavior among adolescents and adults. Whether this hypothesis applies to prosocial-related understanding of others' mental states remains unclear. The present study investigated associations between basal testosterone, basal cortisol (and cortisol awakening response [CAR]), and the cognitive/affective theory of mind (ToM) in 243 adolescents (67.9 % male, aged 14 to 17 years, Mage = 16.09, standard deviation = 0.62). Cognitive ToM (cToM) and affective ToM (aToM) were assessed with a cartoon story reasoning task: In the cToM condition, participants viewed a comic strip story and needed to predict what would happen based on a character's intentions, and in the aToM condition, they viewed a comic strip of two characters interacting and needed to think about what would make the protagonist feel better. The results showed that basal testosterone and basal cortisol did not interact with each other to affect the performance of ToM, either in terms of ToM accuracy or response speed. However, under the condition of low CAR, testosterone is associated with the fast performance of cToM, although the interaction of testosterone and CAR occurred only in female adolescents. Overall, our data provide new evidence for the dual-hormone hypothesis and further extend the hypothesis to social understanding.

Rise and shine: The use of polychromatic short-wavelength-enriched light to mitigate sleep inertia at night following awakening from slow-wave sleep.

Sleep inertia is the brief period of performance impairment and reduced alertness experienced after waking, especially from slow-wave sleep. We assessed the efficacy of polychromatic short-wavelength-enriched light to improve vigilant attention, alertness and mood immediately after waking from slow-wave sleep at night. Twelve participants (six female, 23.3 ± 4.2 years) maintained an actigraphy-confirmed sleep schedule of 8.5 hr for 5 nights, and 5 hr for 1 night prior to an overnight laboratory visit. In the laboratory, participants were awakened from slow-wave sleep, and immediately exposed to either dim, red ambient light (control) or polychromatic short-wavelength-enriched light (light) for 1 hr in a randomized crossover design. They completed a 5-min Psychomotor Vigilance Task, the Karolinska Sleepiness Scale, and Visual Analogue Scales of mood at 2, 17, 32 and 47 min after waking. Following this testing period, lights were turned off and participants returned to sleep. They were awakened from their subsequent slow-wave sleep period and received the opposite condition. Compared with the control condition, participants exposed to light had fewer Psychomotor Vigilance Task lapses (χ2 [1] = 5.285, p = 0.022), reported feeling more alert (Karolinska Sleepiness Scale: F1,77  = 4.955, p = 0.029; Visual Analogue Scalealert : F1,77  = 8.226, p = 0.005), and reported improved mood (Visual Analogue Scalecheerful : F1,77  = 8.615, p = 0.004). There was no significant difference in sleep-onset latency between conditions following the testing period (t10  = 1.024, p = 0.330). Our results suggest that exposure to polychromatic short-wavelength-enriched light immediately after waking from slow-wave sleep at night may help improve vigilant attention, subjective alertness, and mood. Future studies should explore the potential mechanisms of this countermeasure and its efficacy in real-world environments.

The Combination of N60 with Mismatch Negativity Improves the Prediction of Awakening from Coma.

BACKGROUND: Our objective was to evaluate the use of event-related potentials and the middle-latency somatosensory evoked potential (MLSEP) for the prediction of awakening in coma, determine the evaluation day that evoked potentials (EPs) best predict an awakening outcome, and determine whether the mismatch negativity (MMN) combined with the MLSEP, when recorded at 7 days after coma, improved the prediction of awakening from coma. METHODS: Design prospective blinded cohort study. Setting neurointensive care unit of a university hospital. Patients 113 consecutive patients who were severely comatose, whose etiologies of coma included stroke (65 patients), hypoxic-ischemic encephalopathy (28 patients), intracranial infection (6 patients), and other (14 patients). Interventions none. Measurements we gathered Glasgow Coma Scale scores and recorded EPs for all patients who were comatose at 7, 14, and 30 days after coma onset, unless the patients returned to consciousness. The EPs examined included the MLSEP, the middle-latency auditory evoked potential, the N100, and the MMN. With telephone follow-up after 3 months, the patients were classified as awakening or nonawakening according to Glasgow Outcome Scale. RESULTS: When predicting an awakening outcome, at least the unilateral presence of the N60 had the highest sensitivity (82.7%), whereas the presence of the MMN showed the highest specificity (82.0%). The area under the receiver operating characteristic curve for the EPs were high at 7 days after coma onset. At 7 days after coma onset, the combination of the N60 and MMN offered good predictive performance for awakening (area under the receiver operating characteristic curve = 0.852, 95% confidence interval 0.765-0.940), with increased sensitivity (70.0%) and improved specificity (91.7%). CONCLUSIONS: The N60 and MMN were the strongest prognostic factors for an awakening outcome. Furthermore, at 7 days after coma onset, the combination of the N60 and MMN improved the prediction of an awakening outcome in patients who were comatose.

Event-Related Potential Study of Recovery of Consciousness during Forced Awakening from Slow-Wave Sleep and Rapid Eye Movement Sleep.

This work aimed to study the recovery of consciousness during forced awakening from slow-wave sleep (SWS) and rapid eye movement sleep (REM) in healthy volunteers. To track the changes in the degree of awareness of the stimuli during the transition to wakefulness, event-related potentials (ERPs) and motor responses (MR) in the auditory local-global paradigm were analyzed. The results show that during awakening from both SWS and REM, first, alpha-activity restores in the EEG, and only 20 and 25 s (for REM and SWS awakenings, respectively) after alpha onset MR to target stimuli recovers. During REM awakening, alpha-rhythm, MR, and conscious awareness of stimuli recover faster than during SWS awakening. Moreover, pre-attentive processing of local irregularities emerges earlier, even before alpha-rhythm onset, while during SWS awakening, the local effect we registered only after alpha restoration. The P300-like response both on global and local irregularities was found only when accurate MR was restored. Thus, the appearance in EEG predominating alpha-activity is insufficient either for conscious awareness of external stimuli or for generating MR to them. This work may help to understand the pathophysiology of sleep disorders well as conditions characterized by the dissociation between behavior and various aspects of consciousness.

Dissident women's letter writing as decolonial plurilogues of relational solidarities for epistemic justice.

Braiding our words, "dissi-dance," and desires, this article engages how various social actors, and communities-which we are a part of and belong to-challenge structural violence, oppression, inequity, and social, racial, and epistemic injustice. We thread these reflections through our written words, in subversive letters which we offer in the form of a written relational conversation among us: a plurilogue that emerges in response to our specific locations, commitments, and refusals, as well as dissents. Our stories and process of dissent within the various locations, relationships, and contexts that we occupy served as the yarn and needle to thread our stories, posed questions and reflections. Braiding, threading and weaving together, we animate deep decolonial inquiries within ourselves, and our different cultural contexts and countries. Refusing individualism-the illusions of objectivity as distance, the academic as expert, and the exile of affect and emotion on academic pages-we choose to occupy academic writing and ask: What if academic writing were stitched with blood and laughter, relationships and insights, rage and incites? What if, at the nexus of critical psychology and decolonizing feminism, we grew an "embodied praxis?" Unlike academic writing, traditionally designed to camouflage affect, connection, relationality and subjectivity, these letters are unapologetically saturated in care and wisdom toward a narrative-based embodied practice: decolonial plurilogues of relational solidarities for epistemic justice. Our plurilogue of dissent offers a view to advance community research and action with goals of liberation, decoloniality, and community wellness.