Wake Phase Research Articles

Effect of nelonemdaz for patients with out-of-hospital cardiac arrest: the AWAKE phase II randomised clinical trial

Abstract Background Hypoxic brain injury is a major hurdle that limits the survival of out-of-hospital cardiac arrest (OHCA). Nelonemdaz is a dual-target neuroprotectant, serving as a moderate NR2B-selective N-methyl-D-aspartate (NMDA) receptor antagonist while also exhibiting potent free radical scavenger properties. This dual neuroprotective action of nelonemdaz has the potential to reduce hypoxic brain injury in OHCA. We investigated the efficacy and safety of nelonemdaz for patients with OHCA. Methods AWAKE trial was a double-blind, placebo-controlled, randomised, multicentre phase II trial at 5 sites in South Korea. OHCA patients undergoing targeted temperature management were randomly assigned to high-dose (5250 mg), low-dose (3250 mg), and placebo groups at a 1:1:1 ratio. The primary outcome was the blood level of neuron-specific enolase (NSE) after 4th administration of drug. Secondary outcomes comprised blood biomarkers including neuron specific enolase (NSE) and S100beta, brain magnetic resonance imaging (MRI), and Cerebral Performance Category (CPC) and Modified Rankin Scale (mRS) up to day 90. Safety is assessed by serious adverse event. Findings: A total of 105 patients were enrolled between November 18, 2018 to February 23, 2023. Patients with a median age of 61 years and 82% male were assigned to the high-dose (N=37), low-dose (N=35), and placebo (N=33) groups. Primary outcome was evaluated in 93 patients. There was no difference of neuron specific enolase (NSE, ng/mL), which served as the primary endpoint, between high-dose (median and interquartile range; 23·7, 15·0–69·9) and placebo (17·5, 13·6–113·0) groups and also between low-dose (26·6, 16·2–83·4) versus placebo groups (all p>0·05). Among secondary outcomes, fractional anisotropy of brain MRI was significantly higher in high-dose group compared to placebo group (0·465, 0·449–0·485 versus 0·441, 0·431–0·464; p=0·028), and was not different between low-dose (0·462, 0·439–0·480) and placebo groups (p>0·05). At day 90, the common odds ratio (95% confidence interval) indicating a favourable shift in the modified Rankin Scale was 1·25 (0·48–3·24) and 1·22 (0·47–3·20) in the high-dose and low-dose groups respectively, compared to placebo group (all p>0·05). No serious adverse events were reported. Interpretation: Nelonemdaz did not reduced blood NSE level of OHCA patients. However, patients treated with high-dose nelonemdaz showed better fractional anisotropy that suggests reduced cerebral white matter damage. Patients treated with nelonemdaz also showed a favourable tendency of neurological recovery at day 90 without significant adverse effects. These results justify the initiation of a large-scale phase III trial.Neurological function up to day 90

Adenosine 2A Receptors Link Astrocytic Alpha-1 Adrenergic Signaling to Wake-Promoting Dopamine Neurons

BACKGROUNDSleep and arousal disorders are common, but the underlying physiology of wakefulness is not fully understood. The locus coeruleus promotes arousal via alpha-1 adrenergic receptor (α1AR) driven recruitment of wake-promoting dopamine (DA) neurons in the ventral periaqueductal gray (vPAGDA neurons). α1AR expression is enriched on vPAG astrocytes, and chemogenetic activation of astrocytic Gq signaling promotes wakefulness. Astrocytes can release extracellular "gliotransmitters," such as ATP and adenosine, but the mechanism underlying how vPAG astrocytic α1ARs influence sleep/wake behavior and vPAGDA neuron physiology is unknown. METHODSIn this study, we utilized genetic manipulations with ex vivo calcium imaging in vPAGDA neurons and astrocytes, patch-clamp electrophysiology, and behavioral experiments in mice to probe our hypothesis that astrocytic α1ARs mediate noradrenergic modulation of wake-promoting vPAGDA neurons via adenosine signaling. RESULTSActivation of α1ARs with phenylephrine increased calcium transients in vPAGDA neurons and vPAG astrocytes, and increased vPAGDA neuron excitability ex vivo. Chemogenetic Gq-DREADD activation of vPAG astrocytes similarly increased vPAGDA neuron calcium activity and intrinsic excitability. Conversely, shRNA knockdown of vPAG astrocytic α1ARs reduced the excitatory effect of phenylephrine on vPAGDA neurons and blunted arousal during the wake phase. Pharmacological blockade of adenosine 2A (A2A) receptors precludes the α1AR-induced increase in vPAGDA calcium activity and excitability in brain slices, as well as the wake-promoting effects of vPAG α1AR activation in vivo. CONCLUSIONSWe have identified a crucial role for vPAG astrocytic α1AR receptors in sustaining arousal through heightened excitability and activity of vPAGDA neurons mediated by local A2A receptors.

Wake-Sleep Consolidated Learning.

We propose wake-sleep consolidated learning (WSCL), a learning strategy leveraging complementary learning system (CLS) theory and the wake-sleep phases of the human brain to improve the performance of deep neural networks (DNNs) for visual classification tasks in continual learning (CL) settings. Our method learns continually via the synchronization between distinct wake and sleep phases. During the wake phase, the model is exposed to sensory input and adapts its representations, ensuring stability through a dynamic parameter freezing mechanism and storing episodic memories in a short-term temporary memory (similar to what happens in the hippocampus). During the sleep phase, the training process is split into nonrapid eye movement (NREM) and rapid eye movement (REM) stages. In the NREM stage, the model's synaptic weights are consolidated using replayed samples from the short-term and long-term memory and the synaptic plasticity mechanism is activated, strengthening important connections and weakening unimportant ones. In the REM stage, the model is exposed to previously-unseen realistic visual sensory experience, and the dreaming process is activated, which enables the model to explore the potential feature space, thus preparing synapses for future knowledge. We evaluate the effectiveness of our approach on four benchmark datasets: CIFAR-10, CIFAR-100, Tiny-ImageNet, and FG-ImageNet. In all cases, our method outperforms the baselines and prior work, yielding a significant performance gain on continual visual classification tasks. Furthermore, we demonstrate the usefulness of all processing stages and the importance of dreaming to enable positive forward transfer (FWT). The code is available at: https://github.com/perceivelab/wscl.

Slow-wave sleep drives sleep-dependent renormalization of synaptic AMPA receptor levels in the hypothalamus.

According to the synaptic homeostasis hypothesis (SHY), sleep serves to renormalize synaptic connections that have been potentiated during the prior wake phase due to ongoing encoding of information. SHY focuses on glutamatergic synaptic strength and has been supported by numerous studies examining synaptic structure and function in neocortical and hippocampal networks. However, it is unknown whether synaptic down-regulation during sleep occurs in the hypothalamus, i.e., a pivotal center of homeostatic regulation of bodily functions including sleep itself. We show that sleep, in parallel with the synaptic down-regulation in neocortical networks, down-regulates the levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hypothalamus of rats. Most robust decreases after sleep were observed at both sites for AMPARs containing the GluA1 subunit. Comparing the effects of selective rapid eye movement (REM) sleep and total sleep deprivation, we moreover provide experimental evidence that slow-wave sleep (SWS) is the driving force of the down-regulation of AMPARs in hypothalamus and neocortex, with no additional contributions of REM sleep or the circadian rhythm. SWS-dependent synaptic down-regulation was not linked to EEG slow-wave activity. However, spindle density during SWS predicted relatively increased GluA1 subunit levels in hypothalamic synapses, which is consistent with the role of spindles in the consolidation of memory. Our findings identify SWS as the main driver of the renormalization of synaptic strength during sleep and suggest that SWS-dependent synaptic renormalization is also implicated in homeostatic control processes in the hypothalamus.

Weekday and weekend sleep times across the human lifespan: a model-based simulation.

The shifts in the opposite directions, toward later and earlier sleep timing, occur during the transition through adolescence and adulthood, respectively. Such a n-shape of age-associated change in sleep timing does not resemble the inverse relationship of sleep duration with ages. Age-associated variation in the parameters of the mechanisms of circadian and homeostatic regulation of sleep would underlie these different shapes of relationship of sleep times with ages. Here, we searched for a parsimonious explanation of these different shapes by simulating sleep times on weekdays and weekends with one of the variants of the two-process model of sleep regulation. Using mean age of a sample with reported sleep times on weekdays and weekends, the whole set of 1404 such samples was subdivided into 15 age subsets. Simulations of sleep times in these subsets were performed with and without the suggestion of age-associated variation in the circadian phase. Simulations showed that the age-associated decay of slow-wave activity can parsimoniously explain not only the parallel decreases in weekend sleep duration and rate of the buildup of sleep pressure during the wake phase of the sleep-wake cycle, but also both the delay and advance of sleep timing during the transition through adolescence and adulthood, respectively. The almost functional relationships were revealed between the age-related changes in sleep duration, rate of the buildup of sleep pressure, and slow-wave activity that is a good electrophysiological marker of cortical metabolic rate and synaptic density, strength and efficacy.

Design and Implementation of Cost-Effective Assurance Engineering Using Wake-Sleep Algorithm-Based WideResNet with Nonlinear Analysis and Topology Integration

The proliferation of artificial intelligence (AI) in recent years has resulted in an increase in the AI-driven applications across diverse fields. The assurance of the credibility of these AI systems has emerged as a crucial worry. This paper introduces a new model for achieving cost-effective assurance engineering by employing the Wake-Sleep algorithm with the WideResNet architecture. The Wake-Sleep method is utilized in unsupervised learning. This methodology improves the comprehensibility of AI but also establishes a basis for cost-efficient assurance engineering. The Wake-Sleep algorithm has two distinct phases: the Wake Phase, which entails the generative model using actual data, and the Sleep Phase, which enhancement of the encoder through the generated data utilization. The framework is the WideResNet neural network design, which is widely recognized for its effectiveness. The characteristics offer an equilibrium between computational resources and model performance, making it a viable choice for cost-effective solution.

Sleep Disturbance in Bipolar Disorder. Treatment Implications

IntroductionRelationship between sleep and bipolar disorder involves the following aspects: decreased need for sleep is a fundamental marker of the manic state, sleep deprivation is one cause of mania and may in fact be a fundamental etiological agent in mania, total sleep time is a predictor of future manic episodes, and total sleep time may be a marker of response as well as a target of treatment in mania.ObjectivesThis e-poster aimed to summarize evidence regarding the sleep disturbance in Bipolar Disorder.MethodsBibliopgraphical review was performed using PubMed platform. All relevant articles were found using the keywords: sleep disturbance, bipolar disorder, mania.ResultsSleep disturbances are frequent in BD patients in different phases of illness, including the euthymic state and remission. These sleep aberrations are represented not only by insomnia but also by sleep–wake rhythm disorders, especially delayed sleep–wake phase disorders. During the manic state, most patients experience a reduced need for sleep and longer sleep onset latency. Likewise, in the depressive state, insomnia and hypersomnia are commonly observed. Meta-analyses of trials conducted on remitted BD patients demonstrated prolonged total sleep time, increased awakenings after sleep onset, greater variability of sleep–wake variables, and reduced sleep efficiency.ConclusionsOverall, all kinds of sleep disorders and parasomnias are very common especially in youth patients with BD. Thus, compared to the general population, youth with BD exhibit lower sleep efficiency, longer slow wave sleep, and reduced REM sleep, features that could affect the genesis and prognosis of the disorder. Sleep disturbances may also be used as predictors of the onset of BD in a subset of high-risk young subjects.Disclosure of InterestNone Declared

Comparison of actigraphy with a sleep protocol maintained by professional caregivers and questionnaire-based parental judgment in children and adolescents with life-limiting conditions

BackgroundActigraphy offers a promising way to objectively assess pediatric sleep. Aim of the study was investigating the extent to which actigraphy used in children and adolescents with life-limiting conditions is consistent with two other measures of sleep diagnostics.MethodsIn this monocentric prospective study N = 26 children and adolescents with life-limiting conditions treated on a pediatric palliative care unit were assessed. For three consecutive nights they wore an actigraph; the 24-hours sleep protocol documented by nurses and the Sleep Screening for Children and Adolescents with Complex Chronic Conditions (SCAC) answered by parents were analyzed. Patient characteristics and the parameters sleep onset, sleep offset, wake after sleep onset (WASO), number of wake phases, total sleep time (TST) and sleep efficiency (SE) were descriptively examined. Percentage bend correlations evaluated the three measures’ concordance.ResultsDescriptively, and except for the number of waking episodes, the different measures’ estimations were comparable. Significant correlations existed between actigraphy and the sleep protocol for sleep onset (r = 0.83, p = < 0.001) and sleep offset (r = 0.89, p = < 0.001), between actigraphy and SCAC for SE (r = 0.59, p = 0.02).ConclusionAgreement of actigraphy with the focused sleep measures seems to be basically given but to varying degrees depending on the considered parameters.

Can the Brain's Thermostatic Mechanism Generate Sleep-Wake and NREM-REM Sleep Cycles? A Nested Doll Model of Sleep-Regulating Processes.

Evidence is gradually accumulating in support of the hypothesis that a process of thermostatic brain cooling and warming underlies sleep cycles, i.e., the alternations between non-rapid-eye-movement and rapid-eye-movement sleep throughout the sleep phase of the sleep-wake cycle. A mathematical thermostat model predicts an exponential shape of fluctuations in temperature above and below the desired temperature setpoint. If the thermostatic process underlies sleep cycles, can this model explain the mechanisms governing the sleep cyclicities in humans? The proposed nested doll model incorporates Process s generating sleep cycles into Process S generating sleep-wake cycles of the two-process model of sleep-wake regulation. Process s produces ultradian fluctuations around the setpoint, while Process S turns this setpoint up and down in accord with the durations of the preceding wake phase and the following sleep phase of the sleep-wake cycle, respectively. Predictions of the model were obtained in an in silico study and confirmed by simulations of oscillations of spectral electroencephalographic indexes of sleep regulation obtained from night sleep and multiple napping attempts. Only simple-inverse exponential and exponential-functions from the thermostatic model were used for predictions and simulations of rather complex and varying shapes of sleep cycles during an all-night sleep episode. To further test the proposed model, experiments on mammal species with monophasic sleep are required. If supported, this model can provide a valuable framework for understanding the involvement of sleep-wake regulatory processes in the mechanism of thermostatic brain cooling/warming.

Anaesthetic considerations and challenges during awake craniotomy.

This article summarises the key anaesthetic considerations and challenges surrounding the perioperative management of a patient undergoing awake craniotomy. The main goals include patient comfort, facilitation of patient cooperation during the critical awake phase and maintenance of optimal operating conditions. These are achieved through appropriate patient selection and preparation, familiarity with the complexity of each surgical phase and potential complications that may arise, as well as maintenance of close communication among all team members. Challenges such as loss of patient cooperation, loss of airway, intraoperative nausea and vomiting, seizures, cerebral oedema, hypertension, blood loss and use of intraoperative magnetic resonance imaging are discussed. The importance of teamwork, competence, vigilance and clear management strategies for potential complications to maximise patient outcomes is also highlighted.

COMORBID DISORDERS OF THE SLEEP CYCLE – AWAKENESS IN KINDLING RATS UNDER THE CONDITIONS OF USING THE H₃ RECEPTOR ANTAGONIST PITOLISANT

Studies of the neuropathophysiological mechanisms of chronic epileptic activity, whicharise with the participation of the endogenous histaminergic system of the brain, allowus to justify effective complex means of controlling both convulsive manifestations andcomorbid states, which include sleep and wakefulness disorders.Aim of the work – to study the characteristics of the sleep-wake cycle in rats with PTZinduced kindling under the condition of using the H3 receptor antagonist pitolisant.Methods. The kindling syndrome was induced in Wistar rats by daily administration ofpentylenetetrazole (PTZ) (35.0 mg/kg, i. p.) for three weeks. In rats in the course of kindlingdevelopment, pitolisant (5,0 mg/kg, i. p.) was used for 30 min before epileptogen administration.Research results. In rats with developed kindling, the paradoxical sleep phase wasreduced to 7,1% of the total observation period (4 hours) and its fragmentation increased39,7% and the latent period of paradoxical sleep was 24,0% less compared to the controlgroup (P&lt;0,05). Pitolizant treatment was accompanied by an increase in the durationof the awake phase, which was 29% of the total observation time (P&gt;0,05). At the sametime, the duration of paradoxical sleep was 11,6% (P&gt;0,05), and the slow-wave sleepphase was 71,0% (P&gt;0,05). The number of sleep-wake cycles unreliably exceeded theindicator in the control group 17,2% (P&gt;0,05). Latent periods of falling asleep exceededthe indicator in the control group 44,1% (P&lt;0,05) and at the same time was higher thanin kindling rats 60,2% (P&lt;0,05). The latency period of paradoxical sleep was 34.2%higher than kindling rats (P&lt;0.05). &#x0D; Conclusions. The formation of PTZ-kindling is accompanied by a reduction in the latent period of emergence and the total duration of the paradoxical phase of sleep, as well as an increase in its fragmentation. Blocking of H3 histamine receptors by pitolisan during the formation of kindling by administration of pentylenetetrazol prevents the occurrence of wake-sleep cycle disorders.

Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Resting phase-administration of lemborexant ameliorates sleep and glucose tolerance in type 2 diabetic mice

Sleep disorders are associated with increased risk of obesity and type 2 diabetes. Lemborexant, a dual orexin receptor antagonist (DORA), is clinically used to treat insomnia. However, the influence of lemborexant on sleep and glucose metabolism in type 2 diabetic state has remained unknown. In the present study, we investigated the effect of lemborexant in type 2 diabetic db/db mice exhibiting both sleep disruption and glucose intolerance. Single administration of lemborexant at the beginning of the light phase (i.e., resting phase) acutely increased total time spent in non-rapid eye movement (NREM) and REM sleep in db/db mice. Durations of NREM sleep-, REM sleep-, and wake-episodes were also increased by this administration. Daily resting-phase administration of lemborexant for 3–6 weeks improved glucose tolerance without changing body weight and glucose-stimulated insulin secretion in db/db mice. Similar improvement of glucose tolerance was caused by daily resting-phase administration of lemborexant in obese C57BL/6J mice fed high fat diet, whereas no such effect was observed in non-diabetic db/m+ mice. Diabetic db/db mice treated daily with lemborexant exhibited increased locomotor activity in the dark phase (i.e., awake phase), although they did not show any behavioral abnormality in the Y-maze, elevated plus maze, and forced swim tests. These results suggest that timely promotion of sleep by lemborexant improved the quality of wakefulness in association with increased physical activity during the awake phase, and these changes may underlie the amelioration of glucose metabolism under type 2 diabetic conditions.

MYC to BCL6 State-Transitions Determine Cell Size and Metabolic Fluctuations and Define a Novel Biorhythm in B-Cell Malignancies

Background: Cell size fluctuations are well-documented during critical transitions during normal B-cell development. For instance, during early stages of development, “large cycling pre-B cells” (also classified as Fraction C') eventually exit cell cycle and shrink to become “small resting pre-B cells” (Fraction D) to enable immunoglobulin light chain gene recombination. We and others had shown that this transition is marked by loss of Myc expression and gain of Bcl6. Later in development, germinal center B-cells cycle between large MYC+ “centroblast” and smaller BCL6+ “centrocyte” states between dark and light zones, respectively. MYC is involved in biomass accumulation and provides fuel for cell division, while BCL6 confers a quiescent phenotype to cells and protects B cells from DNA damage-induced apoptosis. BCL6 can suppress MYC transcription, indicating MYC and BCL6 is mutually exclusive, and their expression dictates distinct cellular states. Significance: In B-cell malignancies, transitions between mutually exclusive MYC+ and BCL6+ states seem to be important as well: B-ALL cells that are driven by oncogenic tyrosine kinases (e.g. BCR-ABL1) express predominantly MYC but can be forced into a BCL6+ state upon tyrosine kinase inhibition (e.g. imatinib). In germinal center-derived B-cell lymphoma, both MYC and BCL6 are frequently targeted by chromosomal translocation, suggesting that disruption of physiological state transitions may be part of the malignant transformation program. Results: To elucidate regulation of MYC-BCL6 state transitions and their importance in progression and development of drug resistance in B-ALL and germinal center-derived B-cell lymphoma, we developed a MYC-eGFP and BCL6-mCherry dual-reporter mouse model. In addition, we engineered human B-ALL PDX cells with MYC-mNeonGreen and BCL6mScarlet knockin fusion genes by CRISPR/Cas9-mediated HDRT. As expected, MYC+ and BCL6+ states were largely mutually exclusive during early stages of B-cell development, as well as in BCR-ABL1- and NRAS G12D-driven B-ALL. Interestingly, a large fraction of B-ALL cells expressed neither MYC nor BCL6, as validated by cell sorting and Western blot. Based on single-cell sorting and subsequent time-lapse monitoring over 12 hours, we found MYC+ cells transitioning through a double-negative state to become BCL6+ and then revert again to a MYC+ state ( Figure A), suggesting dynamic transitions between MYC and BCL6 cycles. We characterized these populations by analyzing cell size, cell proliferation, cell cycle, clone formation, and gene expression profiles. The results indicated that MYC+ cells exhibited larger cell size, active proliferation, and increased glycolytic activity. Conversely, BCL6+ cells displayed smaller cell size, activation of autophagy with suppression of glycolysis, and cell cycle arrest in the G0 phase of the cell cycle. Conclusions and future directions: Given the dynamic inter-transition between MYC and BCL6 states, and the significant roles of both MYC and BCL6 in B-ALL and germinal center-derived B-cell lymphomas, we propose MYC- and BCL6-dependent fluctuations of cellular activity (wake) and quiescence (sleep; Figure B). Thereby, MYC and BCL6 are expressed in an oscillatory manner. During the MYC state, cells exhibit high glycolysis activity, actively accumulate biomass, and undergo proliferation, representing the wake phase. In contrast, during the BCL6 state, cells suppress glycolysis metabolism, pause the cell cycle, and display a quiescent phenotype, representing the sleep phase. Based on this discovery, we will examine the ‘B-cell exhaustion’ paradigm that Bcl6 and Myc mark iterative cycles of quiescence and activation. In analogy to sleep-wake phases, we hypothesize that the Bcl6-autophagy phase is essential for recovery and regeneration. We will investigate how B-cells transition from one phase to the next and consequences of elongation of one phase at the expense of the other. Malignant B-cells may be particularly sensitive to shortening of quiescence periods (“sleep deprivation”). These and other observations will lead to new conceptual frameworks for the understanding of how MYC-BCL6 state transitions, cell-size fluctuations and the length of recovery-periods regulate energy-supply and survival of B-cell malignancies and create opportunities for therapeutic intervention.

P11.81.B PRELIMINARY RESULTS FROM A RETROSPECTIVE STUDY OF AWAKE CRANIOTOMIES WITH INTRAOPERATIVE MAPPING IN YOUNG ADULTS WITH GLIOMA

Abstract BACKGROUND Awake craniotomy with intraoperative mapping (ACWM) has been proven beneficial in achieving maximal resection of gliomas in eloquent brain areas while preserving neurological function, thus maintaining onco-functional balance. The present study aimed to describe the intraoperative symptoms not related to resection induced deficits in young adult glioma patients during ACWM. METHODS A retrospective, descriptive study of young adults (18-39 years of age) with glioma operated with ACWM in Copenhagen between 2016 and 2022. Patients were identified using the hospital operation booking system cross-referenced with the patient coding system. All data was available in and extracted from the Epic Systems healthcare software used at the hospital. RESULTS So far 37 patients with glioma (median age 31 years, range 21-39 years; 51% females; 78% high-grade gliomas) have been included, constituting 46 planned ACWMs. Most patients (95%) reported some level of intraoperative pain and/or headache with 27% receiving supplemental local anesthetics and 63% receiving supplemental fentanyl or fentanyl analogues during the awake phase. The median for the immediate postoperative Numeric Pain Rating Scale was 1, range 0-7. Intraoperative non-localization specific symptoms included shivering (41%), fatigue (22%), nausea/vomiting (17%), emotionally overwhelm (15%), anxiety (5%) and postoperative vasovagal syncope (5%). Focal seizures were reported in 24% of patients while 1 patient was untimely converted to general anesthesia due to non-convulsive status epilepticus. Operations were terminated due to completed macro-radical resection (32%), reaching the functional limit of resection (63%) and severe fatigue (5%). CONCLUSION Our results represent the practice of a single institution and comply well with previous literature in terms of symptomatic complications not related to resection induced deficits. These symptoms are predominantly simple to manage without the need for untimely termination of surgery. Awake craniotomy with mapping is deemed well-tolerated by young adults and is considered beneficial in optimizing the onco-functional balance of selected glioma patients.

Effects of wake interaction on energy extraction performance of tandem semi-active flapping foils

A numerical investigation was carried out to analyze the interactions between semi-active tandem flapping foils at various tandem distances with a chord-based Reynolds number of 1100. Results indicate that with a tandem distance of less than 1.5 chord lengths and released in-phase, both foils exhibited terminal periodic motions with a nonzero mean stagger distance. In contrast, under the other conditions, the two foils ended up with periodic flapping motions without stagger. Due to the high-pressure region near the leading edge of the aft foil, the heaving motion of the fore foil resulted in lower energy extraction performance than that of single foil, when the tandem distance was less than 5 chord lengths. However, as the tandem distance increased, the fore foil acted like a single foil. The aft foil demonstrated significant fluctuations in performance parameters when subjected to the wake of the fore foil. The favorable interaction between the wake and aft foil resulted in lower power consumption for pitching and enabled the aft foil to extract an additional 15.2% power compared to a single foil. Conversely, during the unfavorable wake–foil interaction, the pitching motion of the aft foil consumed more energy than energy extraction from the heaving motion, leading to net energy consumption. The initial inter-foil pitching phase difference also significantly influenced the performance of the aft foil. Two models, the global phase and the wake phase model, affect these tandem configurations, both proving effective in capturing these effects with the wake phase model displaying notable efficacy.

Association of breakfast styles such as Japanese, Western, and cereals with sleeping habits, eating habits, and lifestyle in preschool and elementary school children.

In Japan, breakfast styles are categorized into five groups; Japanese breakfast (JB; rice and miso soup), Western breakfast (WB; bread and milk), Japanese-Western breakfast (J-WB; alternative daily serving), cereal breakfast (CB), and breakfast skipping. In our recent studies, breakfast style was highly associated with the daily sleep-wake phase (chronotype), and healthy eating habits. In contrast with other breakfast style consumers, JB-consumers were positively associated with the morning chronotype and healthy eating habits such as a high consumption of a variety of protein sources, vegetables, and dietary fibers, and low consumption of sweetened juices. These previous studies included only adult participants; hence, in the current study, we investigated whether similar observations can be made in children. Preschool (aged 3-5 years) and elementary school children (6-8 years) (N = 6,104, 49.87% boys, 50.13% girls, mean body mass index 15.39 ± 0.03 kg/m2 for preschoolers and percentage of overweight -2.73 ± 0.22 for elementary school children) participated in this cross-sectional online survey on lifestyle, including eating and sleep habits, through their mother's responses. The results showed that the morning-evening type index values (chronotype indicator, smaller indicates morning type) were negatively correlated with JB intake (-0.05, p < 0.01) and positively correlated with WB (0.03, p < 0.05) and CB intake (0.06, p < 0.01), suggesting that the JB group exhibited the morning chronotype and the WB and CB groups exhibited the evening chronotype. The JB group consumed a variety of protein sources (mean ± SE; days/week) with more frequency (fish 2.95 ± 0.038 p < 0.001, soy 3.55 ± 0.043 p < 0.001, egg 3.82 ± 0.044 p < 0.001) compared with the WB group (fish 2.58 ± 0.033, soy 3.00 ± 0.038, egg 3.49 ± 0.039). On the other hand, the JB group consumed snacks (5.48 ± 0.042 p < 0.001) and sweetened juice (2.50 ± 0.050 p < 0.001) less frequently than the WB group (snacks; 5.80 ± 0.037 and sweetened juice; 2.74 ± 0.049). JB-eating children with a morning chronotype exhibited better sleep and eating habits than WB-eating children with an evening type pattern. The results suggest that JB eating habits may be associated with good eating and sleeping lifestyles, even among preschool and elementary school children.

THE CLINICAL RELEVANCE OF ADOPTING DIFFERENT DEFINITIONS OF NIGHT-TIME WHEN ASSESSING NOCTURNAL BLOOD PRESSURE

Objective: For hypertension diagnosis, the current European guidelines recommend to combine repeated office readings with use of out-of-office blood pressure (BP) measurements, like ambulatory blood pressure monitoring (ABPM). The drop of systolic BP during night (dipping behaviour) is one of the most important information offered by 24h ABPM. Night-time is most defined as the time period between 22 and 6 h. However, ambulatory sleep studies have shown that individual sleep behaviour is heterogenous. Shifted, shortened, or prolonged time-in-bed (TIB) may lead to changes in classification of dipping behaviour. Additionally, 20% of the population suffers from insomnia, meaning that during TIB patients are partially awake. We investigated nocturnal BP and dipping classification based on actual sleep time vs. individual TIB vs. 22 - 6 h. Design and method: Thirty adults (9 women, mean age 65.1 ± 9.5 years) underwent ABPM via a validated Boso TM- 2430 device. Simultaneously, motor activity and body position were recorded (SOMNOtouch™ NIBP, SOMNOmedics) allowing determination of individual TIB and actual sleep time. Results: In nine patients (30%), individual TIB was shifted by more than two hours, usually being shifted towards later hours. Mean duration of TIB was 7:18h (2:13h to 10:08h). Mean sleep efficiency in individual TIB was 85.6% compared to 72.4% in standard 22 - 6 h. When defining TIB as 22 - 6 h, prevalence of non-dippers was 63% (n = 19). After analysing the corrected TIB, only 37% (n = 11) remained non-dippers. Individual adoption of TIB led to a change in dipping classification in 27% (n = 8) of patients (in all cases from non-dipper to dipper). Considering only BP values during actual sleep, dipping classification changed in another four patients, two patients changing from non-dipper to dipper while two patients changed from dipper to extreme dipper. Conclusions: In 12 out of 30 patients (40%), BP dipping classification changed when adjusting TIB individually and considering BP values during actual sleep. This study highlights that individually determined TIB and exclusion of wake phases during night is of critical importance for a correct assessment of dipping behaviour and may play an important role in optimizing the clinical management of arterial hypertension.

Perioperative seizure in patients undergoing brain mapping under awake craniotomy for language-related eloquent region gliomas: a prospective study.

Awake craniotomy (AC) is standard of care for lesions of eloquent brain areas. One important complication during AC is occurrence of intraoperative seizure (IOS), reported to occur among 3.4-20% of the patients. In this study, we report our experience with IOS during AC for resection of gliomas of the language eloquent regions and evaluate the predisposing factors and consequences. Patients who underwent AC for language related regions of the dominant hemisphere from August 2018 to June 2021 were enrolled. The rate of IOS during AC and relationship between predisposing factors and IOS were evaluated. Sixty-five patients were enrolled (mean age: 44.4±12.5 years). Among 6 patients with IOS (9.2%), only one needed conversion to general anesthesia (GA) due to repeated seizures; while in the remaining 5, AC accomplished successfully despite one seizure attack in the awake phase. Tumor location (especially premotor cortex lesions, P=0.02, uOR:12.0, CI: 1.20-119.91), higher tumor volume (P=0.008, uOR: 1.9, CI: 1.06-1.12) and a functional tumor margin during surgery (P=0.000, uOR: 3.4, CI: 1.47-12.35) were significantly linked with IOS. Occurrence of IOS was associated with a longer ICU stay after surgery and worse immediate neurological outcome, but had no impact on the late neurological status. IOS can usually be managed during AC without need to converting to GA. Those with larger tumors, frontal premotor lesions and positive brain mapping are susceptible to IOS. Early neurological deterioration observed after IOS, seems to be transient with no major long-term consequence on the neurological outcome.

Mobility range, level of pain and sleep quality of patients with venous leg ulcers.

This study aimed to compare mobility range, level of pain and sleep quality in patients with venous leg ulcers to age- and gender-matched controls without ulcers. Twenty patients with venous leg ulceration and 20 matched controls each answered a questionnaire, completed the short-physical performance battery, filled in a subject diary and wore a smartwatch for 1 week. The median daily step counts of the ulcer group (3622 steps/day) and the control group (5133 steps/day) were significantly different (P = .017). Significant correlations between total step count and age, duration of physical outdoor activities and scores in the short-physical performance battery were observed in the ulcer group. The scores in the short-physical performance battery were significantly different in both groups (P = .005), indicating weaker physical performance in the ulcer group. The greatest difference in the self-reported level of pain between the two groups was stated during movement. On average, the ulcer group slept shorter by 1 h 38 min (P = .002) and had 0.7 wake phases per night (P = .019) more than the control group. Assessing mobility in patients with venous leg ulcers can be used to develop preventive and interventional concepts to improve and individualise physical therapies.