The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

[Best evidence summary for awake prone positioning in treating hypoxemic due to COVID-19 infection].

Objective: To retrieve, evaluate, and summarize the best evidence for the treatment of hypoxemia in patients with COVID-19 infection using the awake prone positioning, with the aim of guiding healthcare professionals in the standardized implementation of this therapy. Methods: A systematic search was conducted in databases including UpToDate, BMJ Best Practice, JBI Evidence-Based Healthcare Center, American Association of Critical-Care Nurses, Intensive Care Society, European Respiratory Society, World Health Organization website, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang. The retrieved literature was subjected to quality assessment and evidence extraction. Results: A total of ten publications were included, consisting of one thematic evidence summary, one guideline, two systematic reviews, three randomized controlled trials, and three expert consensus statements. This summary synthesizes thirty key pieces of evidence in five categories: organizational management and training, risk assessment, preparatory operations, implementation key points, and risk control. Conclusions: Awake prone positioning is beneficial for improving hypoxemia in patients with COVID-19 and is easy to implement. Medical institutions should develop nursing management systems, operational standards, and best practices for awake prone positioning based on evidence-based evidence in order to improve the quality of care management for such patients.

A Photoelectrochemical Sensor for Real-Time Monitoring of Neurochemical Signals in the Brain of Awake Animals.

Metal ion homeostasis is imperative for normal functioning of the brain. Considering the close association between brain metal ions and various pathological processes in brain diseases, it becomes essential to track their dynamics in awake animals for accurate physiological insights. Although ion-selective microelectrodes (ISMEs) have demonstrated great advantage in recording ion signals in awake animals, their intrinsic potential drift impairs their accuracy in long-term in vivo analysis. This study addresses the challenge by integrating ISMEs with photoelectrochemical (PEC) sensing, presenting an excitation-detection separated PEC platform based on potential regulation of ISMEs. A flexible indium tin oxide (Flex-ITO) electrode, modified with MoS2 nanosheets and Au NPs, serves as the photoelectrode and is integrated with a micro-LED. The integrated photoelectrode is placed on the rat skull to remain unaffected by animal activity. The potential of ISME dependent on the concentration of target K+ serves as the modulator of the photocurrent signal of the photoelectrode. The proposed design allows deep brain detection while minimizing interference with neurons, thus enabling real-time monitoring of neurochemical signals in awake animals. It successfully monitors changes in extracellular K+ levels in the rat brain after exposure to PM2.5, presenting a valuable analytical tool for understanding the impact of environmental factors on the nervous system.

Automatic sleep-wake classification and Parkinson's disease recognition using multifeature fusion with support vector machine.

AIMS: Sleep disturbance is a prevalent nonmotor symptom of Parkinson's disease (PD), however, assessing sleep conditions is always time-consuming and labor-intensive. In this study, we performed an automatic sleep-wake state classification and early diagnosis of PD by analyzing the electrocorticography (ECoG) and electromyogram (EMG) signals of both normal and PD rats. METHODS: The study utilized ECoG power, EMG amplitude, and corticomuscular coherence values extracted from normal and PD rats to construct sleep-wake scoring models based on the support vector machine algorithm. Subsequently, we incorporated feature values that could act as diagnostic markers for PD and then retrained the models, which could encompass the identification of vigilance states and the diagnosis of PD. RESULTS: Features extracted from occipital ECoG signals were more suitable for constructing sleep-wake scoring models than those from frontal ECoG (average Cohen's kappa: 0.73 vs. 0.71). Additionally, after retraining, the new models demonstrated increased sensitivity to PD and accurately determined the sleep-wake states of rats (average Cohen's kappa: 0.79). CONCLUSION: This study accomplished the precise detection of substantia nigra lesions and the monitoring of sleep-wake states. The integration of circadian rhythm monitoring and disease state assessment has the potential to improve the efficacy of therapeutic strategies considerably.

Modulate the impact of the drowsiness on the resting state functional connectivity.

This research explores different methodologies to modulate the effects of drowsiness on functional connectivity (FC) during resting-state functional magnetic resonance imaging (RS-fMRI). The study utilized a cohort of students (MRi-Share) and classified individuals into drowsy, alert, and mixed/undetermined states based on observed respiratory oscillations. We analyzed the FC group difference between drowsy and alert individuals after five different processing methods: the reference method, two based on physiological and a global signal regression of the BOLD time series signal, and two based on Gaussian standardizations of the FC distribution. According to the reference method, drowsy individuals exhibit higher cortico-cortical FC than alert individuals. First, we demonstrated that each method reduced the differences between drowsy and alert states. The second result is that the global signal regression was quantitively the most effective, minimizing significant FC differences to only 3.3% of the total FCs. However, one should consider the risks of overcorrection often associated with this methodology. Therefore, choosing a less aggressive form of regression, such as the physiological method or Gaussian-based approaches, might be a more cautious approach. Third and last, using the Gaussian-based methods, cortico-subcortical and intra-default mode network (DMN) FCs were significantly greater in alert than drowsy subjects. These findings bear resemblance to the anticipated patterns during the onset of sleep, where the cortex isolates itself to assist in transitioning into deeper slow wave sleep phases, simultaneously disconnecting the DMN.

Glia are powerhouses for sleep.

Glia take up and detoxify neurotoxic lipids on a wake-sleep cycle, in turn promoting healthy sleep.

Impact of specific electromagnetic radiation on wakefulness in mice.

Electromagnetic radiation (EMR) in the environment, particularly in the microwave range, may constitute a public health concern. Exposure to 2.4 GHz EMR modulated by 100 Hz square pulses was recently reported to markedly increase wakefulness in mice. Here, we demonstrate that a similar wakefulness increase can be induced by the modulation frequency of 1,000 Hz, but not 10 Hz. In contrast to the carrier frequency of 2.4 GHz, 935 MHz EMR of the same power density has little impact on wakefulness irrespective of modulation frequency. Notably, the replacement of the 100 Hz square-pulsed modulation by sinusoidal-pulsed modulation of 2.4 GHz EMR still allows a marked increase of wakefulness. In contrast, continuous sinusoidal amplitude modulation of 100 Hz with the same time-averaged power output fails to trigger any detectable change of wakefulness. Therefore, alteration of sleep behavior by EMR depends upon not just carrier frequency but also frequency and mode of the modulation. These results implicate biological sensing mechanisms for specific EMR in animals.

Awake Prone Positioning In COVID Positive Patients: A Retrospective Study.

BACKGROUND: While the advanced health care settings are struggling hard to handle the sudden surge of COVID-19 cases, resource poor settings in developing countries like Nepal can barely stand to fight the increasing number of severe cases. Easily available cost effective interventions would be great blessing for such settings. This study aimed to study if awake prone positioning can be used as such intervention in COVID 19. METHODS: The retrospective study involved 150 patients admitted between November 2020 and January 2021 at Nepal Armed Police Force Hospital and met specific inclusion criteria. Data was obtained at four different time points in relation to prone position and was analysed using International Business Machines Statistical Package for the Social Sciences (SPSS) version 23. RESULTS: It was found that among 150 patients, majority (109; 72.7%) were males and 60(40%) had some comorbidities. The mean oxygen saturation was found to increase significantly from 87.18 %(SD 3.531) to 91.08(SD 2.206) after fifteen minutes of prone positioning. One way ANOVA test showed that there was significant difference in oxygen saturation between at least two time points. (F (3,596) = [180.005], p=0.000). Games Howell Post Hoc test for multiple comparisons showed that the mean value of SPO-2 was significantly different across all four time points, at significance level 0.05. CONCLUSIONS: This study found Awake Prone positioning as a promising cost effective and feasible intervention for improving oxygenation in COVID 19 and thus could be a blessing to the resource poor health care settings.

Distinct lateral hypothalamic CaMKIIα neuronal populations regulate wakefulness and locomotor activity.

For nearly a century, evidence has accumulated indicating that the lateral hypothalamus (LH) contains neurons essential to sustain wakefulness. While lesion or inactivation of LH neurons produces a profound increase in sleep, stimulation of inhibitory LH neurons promotes wakefulness. To date, the primary wake-promoting cells that have been identified in the LH are the hypocretin/orexin (Hcrt) neurons, yet these neurons have little impact on total sleep or wake duration across the 24-h period. Recently, we and others have identified other LH populations that increase wakefulness. In the present study, we conducted microendoscopic calcium imaging in the LH concomitant with EEG and locomotor activity (LMA) recordings and found that a subset of LH neurons that express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) are preferentially active during wakefulness. Chemogenetic activation of these neurons induced sustained wakefulness and greatly increased LMA even in the absence of Hcrt signaling. Few LH CaMKIIα-expressing neurons are hypocretinergic or histaminergic while a small but significant proportion are GABAergic. Ablation of LH inhibitory neurons followed by activation of the remaining LH CaMKIIα neurons induced similar levels of wakefulness but blunted the LMA increase. Ablated animals showed no significant changes in sleep architecture but both spontaneous LMA and high theta (8 to 10 Hz) power during wakefulness were reduced. Together, these findings indicate the existence of two subpopulations of LH CaMKIIα neurons: an inhibitory population that promotes locomotion without affecting sleep architecture and an excitatory population that promotes prolonged wakefulness even in the absence of Hcrt signaling.

Improved data quality and statistical power of trial-level event-related potentials with Bayesian random-shift Gaussian processes.

Studies of cognitive processes via electroencephalogram (EEG) recordings often analyze group-level event-related potentials (ERPs) averaged over multiple subjects and trials. This averaging procedure can obscure scientifically relevant variability across subjects and trials, but has been necessary due to the difficulties posed by inference of trial-level ERPs. We introduce the Bayesian Random Phase-Amplitude Gaussian Process (RPAGP) model, for inference of trial-level amplitude, latency, and ERP waveforms. We apply RPAGP to data from a study of ERP responses to emotionally arousing images. The model estimates of trial-specific signals are shown to greatly improve statistical power in detecting significant differences in experimental conditions compared to existing methods. Our results suggest that replacing the observed data with the de-noised RPAGP predictions can potentially improve the sensitivity and accuracy of many of the existing ERP analysis pipelines.

Functional and oncological outcomes after right hemisphere glioma resection in awake versus asleep patients: a systematic review and meta-analysis.

The right hemisphere has been underestimated by being considered as the non-dominant hemisphere. However, it is involved in many functions, including movement, language, cognition, and emotion. Therefore, because lesions on this side are usually not resected under awake mapping, there is a risk of unfavorable neurological outcomes. The goal of this study is to compare the functional and oncological outcomes of awake surgery (AwS) versus surgery under general anesthesia (GA) in supratentorial right-sided gliomas. A systematic review of the literature according to PRISMA guidelines was performed up to March 2023. Four databases were screened. Primary outcome to assess was return to work (RTW). Secondary outcomes included the rate of postoperative neurological deficit, postoperative Karnofsky Performance Status (KPS) score and the extent of resection (EOR). A total of 32 articles were included with 543 patients who underwent right hemisphere tumor resection under awake surgery and 294 under general anesthesia. There were no significant differences between groups regarding age, gender, handedness, perioperative KPS, tumor location or preoperative seizures. Preoperative and long-term postoperative neurological deficits were statistically lower after AwS (p = 0.03 and p < 0.01, respectively), even though no difference was found regarding early postoperative course (p = 0.32). A subsequent analysis regarding type of postoperative impairment was performed. Severe postoperative language deficits were not different (p = 0.74), but there were fewer long-term mild motor and high-order cognitive deficits (p < 0.05) in AwS group. A higher rate of RTW (p < 0.05) was documented after AwS. The EOR was similar in both groups. Glioma resection of the right hemisphere under awake mapping is a safer procedure with a better preservation of high-order cognitive functions and a higher rate of RTW than resection under general anesthesia, despite similar EOR.

Evaluation of calibrated and uncalibrated optical imaging approaches for relative cerebral oxygen metabolism measurements in awake mice.

Objective. The continuous delivery of oxygen is critical to sustain brain function, and therefore, measuring brain oxygen consumption can provide vital physiological insight. In this work, we examine the impact of calibration and cerebral blood flow (CBF) measurements on the computation of the relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2) from hemoglobin-sensitive intrinsic optical imaging data. Using these data, we calculate rCMRO2, and calibrate the model using an isometabolic stimulus.Approach. We used awake head-fixed rodents to obtain hemoglobin-sensitive optical imaging data to test different calibrated and uncalibrated rCMRO2models. Hypercapnia was used for calibration and whisker stimulation was used to test the impact of calibration.Main results. We found that typical uncalibrated models can provide reasonable estimates of rCMRO2with differences as small as 7%-9% compared to their calibrated models. However, calibrated models showed lower variability and less dependence on baseline hemoglobin concentrations. Lastly, we found that supplying the model with measurements of CBF significantly reduced error and variability in rCMRO2change calculations.Significance. The effect of calibration on rCMRO2calculations remains understudied, and we systematically evaluated different rCMRO2calculation scenarios that consider including different measurement combinations. This study provides a quantitative comparison of these scenarios to evaluate trade-offs that can be vital to the design of blood oxygenation sensitive imaging experiments for rCMRO2calculation.

HD-tDCS mitigates the executive vigilance decrement only under high cognitive demands.

Maintaining vigilance is essential for many everyday tasks, but over time, our ability to sustain it inevitably decreases, potentially entailing severe consequences. High-definition transcranial direct current stimulation (HD-tDCS) has proven to be useful for studying and improving vigilance. This study explores if/how cognitive load affects the mitigatory effects of HD-tDCS on the vigilance decrement. Participants (N = 120) completed a modified ANTI-Vea task (single or dual load) while receiving either sham or anodal HD-tDCS over the right posterior parietal cortex (rPPC). This data was compared with data from prior studies (N = 120), where participants completed the standard ANTI-Vea task (triple load task), combined with the same HD-tDCS protocol. Against our hypotheses, both the single and dual load conditions showed a significant executive vigilance (EV) decrement, which was not affected by the application of rPPC HD-tDCS. On the contrary, the most cognitively demanding task (triple task) showed the greatest EV decrement; importantly, it was also with the triple task that a significant mitigatory effect of the HD-tDCS intervention was observed. The present study contributes to a more nuanced understanding of the specific effects of HD-tDCS on the vigilance decrement considering cognitive demands. This can ultimately contribute to reconciling heterogeneous effects observed in past research and fine-tuning its future clinical application.

Performance of intraoperative neurocognitive tests during awake surgery for patients with diffuse low-grade glioma.

Despite great advancements and the diffusion of awake surgery for brain tumors, the literature shows that the tests applied during the procedure are heterogeneous and non-standardized. This prospective, observational, descriptive study collected data on intraoperative brain mapping and the performance of multiple neurocognitive tests in 51 awake surgeries for diffuse low-grade glioma. Frequency of use and rate of intraoperative findings of different neurocognitive tests were analyzed. Patients mean age at the time of surgery was 35.1 (20-57) years. We performed 26 (51.0%) surgeries on the left hemisphere (LH) and 25 (49.0%) on the right hemisphere (RH). Significant differences were observed between the total number of functional findings (cortical and subcortical) identified in the LH and RH (p = 0.004). In subcortical findings alone, the differences remained significant (p = 0.0004). The RH subcortical region showed the lowest number of intraoperative findings, and this was correlated with functional outcome: Karnofsky performance scale at five days (p = 0.022), three months (p = 0.002) and one year (p = 0.002) post-surgery. On average, more tests were used to map the RH, with a lower frequency of both cortical and subcortical functional findings. Even though subcortical findings were less frequent than cortical findings, they were crucial to defining the resection margins. Based on the intraoperative findings, frequency of use, and rate of findings per use of the tests analyzed, the most relevant tests for each hemisphere for awake brain mapping were identified.

Sleep and subjective age: protect your sleep if you want to feel young.

The current studies examined the impact of insufficient sleep and sleepiness on the subjective experience of age. Study 1, a cross-sectional study of 429 participants (282 females (66%), 144 males, 3 other gender; age range 18-70), showed that for each additional day of insufficient sleep in the last 30 days, subjective age increased by 0.23 years. Study 2, an experimental crossover sleep restriction study (n = 186; 102 females (55%), 84 males; age range 18-46), showed that two nights of sleep restriction (4 h in bed per night) made people feel 4.44 years older compared to sleep saturation (9 h in bed per night). Additionally, moving from feeling extremely alert (Karolinska Sleepiness Scale (KSS) score of 1) to feeling extremely sleepy (KSS score of 9) was associated with feeling 10 years older in both studies. These findings provide compelling support for insufficient sleep and sleepiness to exert a substantial influence on how old we feel, and that safeguarding sleep is probably a key factor in feeling young.

High-density cortical µECoG arrays concurrently track spreading depolarizations and long-term evolution of stroke in awake rats.

Spreading depolarizations (SDs) are widely recognized as a major contributor to the progression of tissue damage from ischemic stroke even if blood flow can be restored. They are characterized by negative intracortical waveforms of up to -20 mV, propagation velocities of 3 - 6 mm/min, and massive disturbance of membrane ion homeostasis. High-density, micro-electrocorticographic (µECoG) epidural electrodes and custom, DC-coupled, multiplexed amplifiers, were used to continuously characterize and monitor SD and µECoG cortical signal evolution in awake, moving rats over days. This highly innovative approach can define these events over a large brain surface area (~ 3.4 × 3.4 mm), extending across the boundaries of the stroke, and offers sufficient electrode density (60 contacts total per array for a density of 5.7 electrodes / mm2) to measure and determine the origin of SDs in relation to the infarct boundaries. In addition, spontaneous ECoG activity can simultaneously be detected to further define cortical infarct regions. This technology allows us to understand dynamic stroke evolution and provides immediate cortical functional activity over days. Further translational development of this approach may facilitate improved treatment options for acute stroke patients.

A midbrain GABAergic circuit constrains wakefulness in a mouse model of stress.

Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions.

[Behavioral management of insomnia]. / Prise en charge comportementale de l'insomnie.

BEHAVIORAL MANAGEMENT OF INSOMNIA. Behavioral management of insomnia aims to bring about lasting changes in the habits of insomniacs, in terms of sleep schedules, regularity, and organization of the day (naps). Eating and exercise habits also need to be restructured and regularized. The two most effective techniques for improving insomniac sleep are time restriction and stimulus control. Reducing the time spent in bed to 6 or 6.5 hours rapidly leads to an improvement in falling asleep and sleep continuity. For the first few weeks, however, this technique may lead to drowsiness, which the patient should be warned about. Stimulus control try to re-establish the bed=sleep signal, by eliminating time spent in bed without sleeping. Relaxation, meditation, and rhythm synchronization are natural complements of these techniques.

PRISE EN CHARGE COMPORTEMENTALE DE L'INSOMNIE. La prise en charge comportementale de l'insomnie vise à modifier durablement les habitudes des insomniaques à la fois sur les horaires de sommeil, leur régularité et sur l'organisation de la journée (sieste). Les habitudes alimentaires et sportives sont également à restructurer et à régulariser. Les deux techniques les plus efficaces pour améliorer le sommeil de l'insomniaque sont les techniques de restriction du temps passé au lit ou de contrôle du stimulus. Réduire le temps passé au lit à six heures ou six heures trente permet une amélioration rapide de l'endormissement et de la continuité du sommeil. Cette technique peut, les premières semaines, entraîner une somnolence dont il faut prévenir le patient. Le contrôle du stimulus essaye de rétablir le signal « lit = sommeil ¼, en faisant la chasse au temps passé au lit sans dormir. La relaxation, la méditation et la synchronisation des rythmes sont les compléments naturels de ces techniques.