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Hai-Hua Chuang,1– 3 Chi-Hung Liu,4 Chao-Yung Wang,5 Yu-Lun Lo,6 Guo-She Lee,7,8 Yi-Ping Chao,4,9 Hsueh-Yu Li,10 Terry BJ Kuo,11 Cheryl CH Yang,11 Liang-Yu Shyu,12 Li-Ang Lee10,11 1Department of Family Medicine, Chang Gung Memorial Hospital, Taipei Branch and Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 2Department of Industrial Engineering and Management, National Taipei University of Technology, Taipei, Taiwan; 3Genomic Medicine Institute & Obesity Institute, Geisinger Medical, Danville, PA, USA; 4Department of Neurology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 5Department of Cardiology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 6Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 7Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 8Department of Otolaryngology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan; 9Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan, Taiwan; 10Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 11Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; 12Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, TaiwanCorrespondence: Li-Ang LeeDepartments of Otorhinolaryngology-Head and Neck Surgery, Sleep Center, Chang Gung Memorial Hospital, Linkou Main Branch, No. 5, Fu-Hsing Street, Guishan District, Taoyuan, 33305, TaiwanTel +886 33281200 ext. 3972Fax +886 33979361Email 5738@cgmh.org.twBackground: Obstructive sleep apnea (OSA) and snoring have been reported to be modifiable risk factors for thick carotid intima-media thickness (CIMT) and carotid atherosclerosis, which are closely linked to cardiovascular disease.Methods: This cross-sectional study prospectively recruited 70 participants with OSA and without a history of carotid artery disorder, who primarily sought surgical Intervention. OSA and snoring were assessed with the Epworth Sleepiness Scale, Snore Outcomes Survey, polysomnography, and snoring sound recording. The carotid arteries were evaluated with ultrasonography and divided into three types of carotid artery profiles (normal carotid artery, thick CIMT, or significant carotid atherosclerosis). Multivariate linear/logistic/categorical regressions were performed with the forward selection approaches/logistic least absolute shrinkage and selection operator, as appropriate.Results: Normalized snoring sound energy (301– 850 Hz) was independently associated with the carotid intima-media thickness (regression coefficient [β] = 0.01, standard error [SE] = 0.004, P = 0.03; R2 = 0.067) and type of carotid profile (β = 0.40, SE = 0.09, P < 0.001; R2 = 0.156). Normalized snoring sound energy (4– 300 Hz) (β = − 0.10, SE = 0.04, P = 0.01) and female sex (β = 1.90, SE = 0.94, P = 0.04) were independently related to the presence of carotid stenosis (R2 = 0.159). The optimal regression model of the type of carotid artery profile included normalized snoring sound energy (301– 850 Hz) (β = 0.33, SE = 0.14, P = 0.03), snoring time (β = 0.26, SE = 0.13, P = 0.047), female sex (β = 0.26, SE = 0.13, P = 0.047), and increased age (β = 0.20, SE = 0.10, P = 0.04) under the control of the Snore Outcomes Survey score, 3% oxygen desaturation index, snoring sound energy (4– 1500 Hz), normalized snoring sound energy (851– 1500 Hz), cigarette smoking, and hyperlipidemia (R2 = 0.427).Conclusion: Our findings suggested that snoring sound characteristics are associated with carotid artery profiles among early OSA patients who cannot be noticed by ultrasound because organic changes of the carotid artery have not yet started. Future studies are warranted to verify the clinical significance of the results.Keywords: atherosclerosis, common carotid artery, categorical regression, obstructive sleep apnea, snoring, ultrasound

Aim and objective. The aim of the study was to analyse, while controlling for identified covariates, the effects of morningness-eveningness on sleep quality for shift nurses. Background. Shift nurses had greater difficulty falling asleep or staying asleep, thus resulting in higher rates of retiring from hospital. Existing research has addressed the effects of manpower demand and personal preferences on shift assignment; however, the concept of endogenous rhythms is rarely considered. Methods. This analysis included 137 nurses between the ages of 21-58. Nurses completed the Horne and Ostberg questionnaire to assess morningness-eveningness and the Pittsburgh Sleep Quality Index (PSQI) questionnaire to measure self-reported sleep quality over the last month. The 18-point Chinese version had a Cronbach's reliability coefficient of 0·79 overall and 0·86 respectively. This study analysed correlates of sleep quality by comparing the groups with better or worse sleep quality according to the median of PSQI. Univariate and multivariate analyses were used for the risk factors of worse sleep quality. Results. The result showed that the strongest predictor of sleep quality was morningness-eveningness not the shift schedule or shift pattern for nurses under controlling the variable of age. Greater age and longer years employed in nursing significantly decreased the risk of worse sleep quality. The confounding age factor was properly controlled; evening types working on changing shifts had higher risk of poor sleep quality compared to morning types. Conclusions. Morningness-eveningness was the strongest predictor of sleep quality under controlling the variable of age in shift nurses. Implications for clinical practice. Our results suggested that determining if nurses were attributed to morning or evening types is an important sleep issue before deciding the shift assignment. [ABSTRACT FROM AUTHOR]

The nasal cavity and its related structures make significant contributions to human phonation, especially the resonance of voice spectra. The voice spectra of the nasal consonant-vowel (CV), [md:], in the subjects with nasal obstruction were obtained and were compared with the spectra of the same CV vocalized by the same subjects after topical nasal decongestion treatment with 1:1000 epinephrine solution. Results revealed that the intensity damping was more marked in the high-frequency area (>1600 Hz) after the nasal decongestion. Moreover, the intensities of the spectral valleys damped more than the spectral peaks, especially the spectral valley of 1000-2700 Hz. Therefore, a more complex spectral pattern was formed by the resultant uneven damping effect after nasal decongestion. The nasal cavity plays an important role in the formation of spectral peaks and valleys, and such engraved voice spectra may also characterize nasal voices like the nasal CV [md:] demonstrated in our study. [ABSTRACT FROM AUTHOR]

Emerging evidence underscores the pivotal role of the gut microbiota in regulating emotional and behavioral responses via the microbiota-gut-brain axis. This study explores associations between pediatric obstructive sleep apnea (OSA), emotional distress (ED), and gut microbiome alterations before and after OSA treatment. Sixty-six children diagnosed with OSA via polysomnography participated, undergoing adenotonsillectomy alongside routine educational sessions. ED was assessed using the OSA-18 questionnaire, categorizing participants into high ED (scores ≥ 11, 52%) and low ED (scores < 11, 48%) groups. Gut microbiome analysis revealed significant diversity differences, with high ED linked to a reduced Shannon index ( p = 0.03) and increased beta diversity ( p = 0.01). Three months post-treatment, significant improvements were observed in OSA symptoms, ED scores, and gut microbiome alpha diversity metrics among 55 participants (all p < 0.04). Moreover, changes in the relative abundances of Veillonella , Bifidobacterium , Flavonifractor , and Agathobacter , as well as ultra-low frequency power and low frequency power of sleep heart rate variability, were independently associated with ED score alterations. These findings underscore the gut microbiome's critical role in the emotional and behavioral symptoms associated with pediatric OSA, suggesting that microbiome-targeted interventions could complement traditional treatments for ED reduction and emphasizing the need for further research.

We aimed to evaluate the presence of sleep-disordered breathing (SDB) in generalized anxiety disorder (GAD) patients and its impacts after 12-week of escitalopram treatment. In this prospective observational study, GAD patients were followed up to determine whether comorbid SDB affects their treatment response. They underwent a home sleep apnea test (HSAT), and oxygen desaturation index ≥5 was considered indicative of SDB. All participants were treated with escitalopram 5 mg in the first 2 weeks and 10 mg in the remaining 10 weeks. They underwent assessments of heart rate variability and completed questionnaires for sleep, mood, attention, and daytime sleepiness on the day of enrollment, and 2 weeks, 4 weeks, and 12 weeks later. A total of 45 GAD participants (mean age, 56.2 years) were included in the study. Of these, 53.3% had comorbid SDB. Participants with GAD and SDB had higher baseline Beck Anxiety Inventory (BAI) and STOP-BANG scores. Both groups of participants with GAD showed overall improvement in anxiety, depression, and insomnia symptoms after 12 weeks of escitalopram treatment. Additionally, there were no statistically significant differences in the changes in BAI, Beck Depression Inventory, and Epworth Sleepiness Scale scores between the two groups at the Week 2, Week 4, and Week 12 assessments compared to baseline. However, the GAD group with comorbid SDB seemed to have a lower tendency for improvement in depressive symptoms than the group with non-comorbid SDB. Compared with the GAD group without comorbid SDB, the GAD group with comorbid SDB exhibited more severe anxiety symptoms at baseline and tended to show less improvement in depressive symptoms after 12 weeks of escitalopram treatment., Competing Interests: Declaration of competing interest The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Obstructive sleep apnea (OSA) is a prevalent disorder, with oral breathing influencing its severity. Expiratory velopharyngeal obstruction (EVO), observed during drug-induced sleep endoscopy (DISE), may contribute to oral breathing in OSA patients. EVO results in obstruction between the pharynx and nasal cavity during expiration. This study aims to identify factors associated with positive EVO during DISE., Study Design: Case series., Setting: Tertiary Medical Center., Methods: Seventy-two OSA patients underwent clinical evaluation, polysomnography, and DISE, utilizing interventions like intraoral negative airway pressure (iNAP), mouth closure, and oral appliances (OAs) in supine positions with head rotation. The findings, classified under velopharynx, oropharynx, tongue base, epiglottis, included the presence of EVO., Results: The results demonstrated that interventions including mouth closure and iNAP were associated with increased observation of EVO (43.1% and 34.7%) compared to OA (20.1%). However, head rotation was associated with decreased presence of EVO during DISE compare to supine (26% vs 35.8%). Noticeably, per 1 year increase of age was associated with an increased odds of EVO (odds ratio: 1.03, 95% confidence interval: 1.01-1.06). However, no other baseline characteristics were significantly associated the odds of EVO., Conclusion: Our study reveals the effectiveness of head rotation and OA in reducing EVO and improving mouth breathing in OSA patients, offering valuable insights for future treatment strategies., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

In this study, we aimed to investigate the relationships between sleep duration and autonomic nervous system (ANS) regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer's disease who were hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity via the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, hypertension status, and medication use (antipsychotics) as covariates. A sleep duration of 6-9 h per night compared to shorter than 6 h was associated with a greater increase in parasympathetic nervous system activity ( p = 0.03), and a sleep duration longer than 9 h was associated with a decrease sympathovagal balance ( p = 0.02). In addition, we observed an inverted U-shaped association between sleep duration and ANS regulation. In this pilot study, we demonstrated that a sleep duration of 6-9 h per night may be beneficial for ANS regulation; however, the present study involved only a few participants and had some limitations. Additional research with a larger cohort is needed to confirm these findings.

Background: Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA., Methods: We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis., Results: We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women., Conclusion: According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women., (© 2024. The Author(s).)

Aims: The probiotic bacterium Levilactobacillus brevis (L. brevis) has been proposed as a potential solution to manage mood disorders and alleviate stress-related sleep disturbances. However, the underlying mechanisms of its effects have not been fully elucidated. The aim of this study was to explore the impact and potential mechanisms of L. brevis SG031 supplementation on anxiety/depression-like behaviors and stress-induced changes in sleep patterns and sleep-related autonomic function., Main Methods: Male Wistar-Kyoto rats were administered low, medium, or high doses of L. brevis SG031 or a vehicle for 4 weeks, followed by behavioral tests to evaluate anxiety and depression. After an additional 2 weeks of SG031 or vehicle administration, a cage-exchange paradigm was performed with 24-hour physiological signal measurements under different stress conditions. Fecal samples were collected to construct a 16S rRNA library and assess fecal short-chain fatty acids (SCFAs)., Key Findings: High-dose SG031 administration yielded reduced depression-like responses and enhanced social interaction in behavioral tests. It also exhibited a protective effect against stress-induced sleep disturbance characterized by decreased sleep time, increased awake time, and autonomic dysfunction during sleep. Fecal examination indicated that high-dose SG031 administration exerted beneficial effects on gut health by maintaining the gut microbial abundance, preserving stability of the microbial composition, and enriching the gut with SCFAs, which were associated with improvements in sleep and autonomic function., Significance: These findings collectively underscore the multifaceted potential of SG031 in addressing mental health and stress-related sleep challenges through the modulation of the gut microbiota., Competing Interests: Declaration of competing interest We had a grant support (YM107C052) from Syngen Biotech Company. The company provided Levilactobacillus brevis SG031 (special screening and cultivation of strains) to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Low values of heart rate deceleration capacity (DC) and heart rate asymmetry (HRA) are associated with cardiovascular risks. Slow respiration has been proven to enhance the magnitudes of these indexes, but individual inspiratory (T I ) and expiratory (T E ) durations were not controlled in most studies. This study aims to examine whether the effects of T I and T E on these indexes would be the same and, if not, how to adjust T I and T E to maximize the effect of slow respiration., Methods: We evaluated 14 seated healthy young adults who randomly controlled their breathing to nine combinations of T I and T E , each chosen respectively from 2, 4, and 6 s. A 5-min R-R interval time series was obtained from each study period for further analysis., Results: The magnitude of DC increased when T I or T E increased, while that of acceleration capacity (AC) remained almost unchanged by T I . We further defined a new index as 100 × DC 2 /(DC 2  + AC 2 ) and found it to be correlated with conventional Guzik's (r = 0.94) and Porta's (r = 0.99) indexes of HRA during different combinations of T I and T E . Increasing T I and increasing T E both enhanced the magnitudes of HRA indexes, with T I taking effect when ≤ 4 s, and T E taking effect when > 4 s. DC and HRA indexes were maximized with a T I of 4 s and a T E of 6 s., Conclusion: We suggest that a T I of 3-4 s with a T E of 7-6 s is an appropriate standard for slow respiration., (© 2024. The Author(s).)

Background: Electroencephalographic pattern changes during anesthesia reflect the nociception-analgesia balance. Alpha dropout, delta arousal, and beta arousal with noxious stimulation have been described during anesthesia; however, data on the reaction of other electroencephalogram signatures toward nociception are scarce. Analyzing the effects of nociception on different electroencephalogram signatures may help us find new nociception markers in anesthesia and understand the neurophysiology of pain in the brain. This study aimed to analyze the electroencephalographic frequency pattern and phase-amplitude coupling change during laparoscopic surgeries., Methods: This study evaluated 34 patients who underwent laparoscopic surgery. The electroencephalogram frequency band power and phase-amplitude coupling of different frequencies were analyzed across 3 stages of laparoscopy: incision, insufflation, and opioid stages. Repeated-measures analysis of variance with a mixed model and the Bonferroni method for multiple comparisons were used to analyze the changes in the electroencephalogram signatures between the preincision and postincision/postinsufflation/postopioid phases., Results: During noxious stimulation, the frequency spectrum showed obvious decreases in the alpha power percentage after the incision (mean ± standard error of the mean [SEM], 26.27 ± 0.44 and 24.37 ± 0.66; P < .001) and insufflation stages (26.27 ± 0.44 and 24.40 ± 0.68; P = .002), which recovered after opioid administration. Further phase-amplitude analyses showed that the modulation index (MI) of the delta-alpha coupling decreased after the incision stage (1.83 ± 0.22 and 0.98 ± 0.14 [MI × 10 3 ]; P < .001), continued to be suppressed during the insufflation stage (1.83 ± 0.22 and 1.17 ± 0.15 [MI × 10 3 ]; P = .044), and recovered after opioid administration., Conclusions: Alpha dropout during noxious stimulation is observed in laparoscopic surgeries under sevoflurane. In addition, the modulation index of delta-alpha coupling decreases during noxious stimulation and recovers after the administration of rescue opioids. Phase-amplitude coupling of the electroencephalogram may be a new approach for evaluating the nociception-analgesia balance during anesthesia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Introduction: The levels of low-density lipoprotein (LDL) cholesterol in plasma are important risk factors for coronary heart disease. Several reports suggest that elevated plasma cholesterol is associated with cardiac arrhythmias. In a subsequent study investigating LDL cholesterol levels and the frequency of LDL cholesterol measurements, a positive correlation was observed between the severity of sleep apnea and visit-to-visit LDL cholesterol variability. Our objective was to assess the effects of hypercholesterolemia on cardiac autonomic activity, disordered sleep patterns, and increased incidence of arrhythmias in freely moving rats., Methods: Wireless transmission of polysomnographic recordings was performed in control and high cholesterol male rats during normal daytime sleep. Spectral analyses were conducted on the electroencephalogram and electromyogram (EMG) recordings to distinguish active waking, quiet sleep, and paradoxical sleep. Heart rate variability power spectrum analysis was used to measure cardiac autonomic activity., Results: The high cholesterol group exhibited a higher low-frequency (LF)/high-frequency (HF) power ratio during all sleep stages compared to the control group. Additionally, the frequency of sleep interruptions was increased in the high cholesterol group compared to the control group., Conclusions: Our results show significant sleep fragmentation with sympathetic hyperactivity after exposure to high cholesterol. This indicates that high cholesterol may increase the risk of sleep apnea and poor sleep quality by disrupting autonomic homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: In patients with obstructive sleep apnea (OSA), epiglottic collapse (EC) constitutes a major factor in the failure of continuous positive airway pressure therapy and uvulopalatopharyngoplasty. This study explored treatments that can improve EC in patients with OSA through drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE)., Study Design: Retrospective cohort study., Setting: Tertiary center., Methods: This study screened 352 OSA patients who underwent TCI-DISE between 2016 and 2022. Fifty-four patients with EC were included in the final analysis. EC severity was assessed multiple times through TCI-DISE with different interventions., Results: The application of these interventions in patients with anteroposterior epiglottic collapse (apEC) led to a significant decrease in apEC severity from total to partial or no obstruction in 60.0% of patients by head rotation, in 53.6% by mouth closure, in 47.4% who received oral appliances (OA), and in 28.0% who received intermittent negative airway pressure (iNAP). With simultaneous head rotation, apEC severity decreased more significantly from total to partial or no obstruction in 77.8% of patients by mouth closure, in 70.3% who received OA, and in 68.0% who received iNAP. Lateral epiglottic collapse (latEC) severity decreased in 53.8% of patients after OA use and in 61.5% of patients with OA use and head rotation., Conclusion: This study identified head rotation with mouth closure as the most effective treatment for apEC through TCI-DISE. Patients with latEC had higher weight, apnea-hypopnea index, and body mass index compared with patients with apEC. OA use with head rotation appeared more effective in latEC through TCI-DISE., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Ethnopharmacological Relevance: Achyranthes aspera, a widely recognized medicinal plant, is used in various cultures for treating different ailments, including renal dysfunction; however, there is a lack of comprehensive understanding of its protective effects and the underlying signaling networks involved., Aim of the Study: This study aimed to investigate the molecular mechanisms of the action of A. aspera by employing an integrative approach including functional and tissue imaging as well as comprehensive genomics analysis., Materials and Methods: Cisplatin-induced nephrotoxicity is a well-established animal model for acute kidney injury (AKI). In this study, we investigated the protective effects and underlying mechanisms of the action of A. aspera water-soluble extract (AAW) on a murine model of cisplatin-induced AKI. The evaluation includes measurements of blood urea nitrogen (BUN) and serum creatinine (SCr) levels, histology examination, and transcriptome analysis using RNA sequencing., Results: In male ICR mice, oral administration of AAW at doses of 0.5-1.0 g/kg significantly reduced cisplatin-induced nephrotoxicity. This effect included the amelioration of tubular injury, renal fibrosis, and the lowering of BUN and SCr levels. AAW also effectively decreased oxidative markers, such as malondialdehyde (MDA) and nitrotyrosine (NT), along with inflammation markers, including COX-2, iNOS, NLRP3, and pP65NFκB. Moreover, AAW administration induced a dose-dependent increase in the expression of two protective factors, Nrf2 and BcL2, and suppressed apoptosis, as evidenced by reduced levels of truncated caspase 3 (t-Casp3). To explore the underlying molecular mechanisms and signaling networks, next-generation sequencing (NGS) analysis was employed. The results revealed that AAW mitigated apoptosis, necroptosis, and PANoptosis pathways by inhibiting inflammation signaling pathways, such as the TNFα-, NFκB-, NETs-, and leukocyte transendothelial migration pathways. Additionally, AAW was found to enhance protective signaling pathways, including the cGMP/PKG-, cAMP-, AMPK-, and mTOR-dependent activation of autophagy and mitophagy pathways. The primary bioactive compound found in AAW was identified as 20-hydroxyecdysone (0.36%)., Conclusion: Our study demonstrates that AAW reduces cisplatin-induced nephrotoxicity. The protective effects of AAW are attributed to its modulation of multiple molecular signaling networks. Specifically, AAW downregulates genes and signaling pathways associated with oxidative stress and endoplasmic reticulum (ER) stress, inflammation, and PANoptosis. Simultaneously, it upregulates genes and signaling pathways associated with cell survival, including autophagy and mitophagy pathways., Competing Interests: Declaration of competing interest All authors of this manuscript have made significant contributions to this study, including active participation in the writing process and approval of this submitted version. This research constitutes original work and has not been previously considered for publication in any other journal. We assure you that it will not be submitted elsewhere as long as the Journal of Ethnopharmacology accepts it. Upon acceptance for publication in the Journal of Ethnopharmacology, the worldwide copyright will be transferred to the publisher on behalf of the journal., (Copyright © 2023. Published by Elsevier B.V.)

Background: Suboptimal health status (SHS) is a dynamic state in which people have not been diagnosed with a disease but tend to develop diseases. People with SHS are more prone to conditions such as cardiovascular disease and metabolic syndrome. Suitable interventions in people with SHS can prevent disease development. SHS is correlated with traditional Chinese medicine (TCM)-based constitutions, including Yang-Xu (yang deficiency), Yin-Xu (yin deficiency), and stasis types. The circadian rhythm is a potential biomarker of health and metabolism. Baduanjin exercise, a kind of mind-body exercise, has been regarded to adjust body constitution and metabolism, but few studies have evaluated the effects of Baduanjin exercise on body constitution and circadian rhythms. Therefore, this randomized controlled trial investigated the effects of Baduanjin exercise on body constitution and circadian rhythms in people with SHS., Methods: Seventy-six participants with SHS were divided into the Baduanjin exercise and control groups (watching a Baduanjin video), with the interventions lasting 12 weeks. The Body Constitution Questionnaire (BCQ), SHS Questionnaire-25 (SHSQ-25), and actigraphy for circadian rhythm measurement were conducted., Results: The scores of SHSQ-25, Yang-Xu, Yin-Xu, and BCQ stasis decreased significantly after 12 weeks in the Baduanjin exercise group, but not in the control group. Interdaily stability of the circadian rhythm increased significantly in the Baduanjin exercise group but not in the control group., Conclusion: This is the first report of improved health status, modulated body constitution, and increased interdaily stability of the circadian rhythm in participants with SHS who practiced Baduanjin exercise., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Importance: Obstructive sleep apnea (OSA) in children is linked with alterations in the gut microbiome. The influence of adenotonsillectomy (AT), a primary intervention for OSA, on gut microbiota dynamics relative to disease severity remains to be elucidated., Objective: This study aimed to investigate the impact of OSA severity and AT on the gut microbiome in pediatric patients., Design: A prospective observational study., Setting: Tertiary referral center., Participants: A cohort of 55 pediatric patients treated with AT for OSA., Intervention: Total tonsillectomy and adenoidectomy procedures., Main Outcome Measures: Comprehensive evaluations included in-laboratory polysomnography and 16S rRNA gut microbiome profiling at baseline, and again at 3rd and 12thmonth following surgery., Results: Initial findings showed uniform α-diversity across different severities of OSA, while β-diversity was significantly elevated in the severe OSA subgroup. Certain gut microbiota taxa ( Lachnospiraceae NK4A136 group , Ruminococcaceae UCG-002 , Ruminococcaceae UCG-014 , Alloprevotella , Christensenellaceae R-7 group , Ruminococcaceae UCG-005 , Lactobacillus murinus , and Prevotella nigrescens ) were found to inversely correlate with the apnea-hypopnea index (AHI). Significant post-AT improvements in AHI and other polysomnographic metrics were observed. Notably, AHI changes post-AT were positively associated with microbial α-diversity (species richness), β-diversity, and specific bacterial taxa ( Enterobacter , Parasutterella , Akkermansia , Roseburia , and Bacteroides plebeius DSM 17135 ), but negatively with other taxa ( Fusicatenibacter , Bifidobacterium , UBA1819 , Ruminococcus gnavus group , Bifidobacterium longum subsp. Longum , and Parabacteroides distasonis ) and specific metabolic pathways (purine metabolism, transcription factors, and type II diabetes mellitus). The postoperative patterns of α- and β-diversity mirrored baseline values., Conclusions and Relevance: This study documents significant changes in the gut microbiome of pediatric patients after AT, including variations in α- and β-diversities, bacterial communities, and inferred metabolic functions. These changes suggest a potential association between the surgical intervention and microbiome alterations, although further studies are necessary to discern the specific contributions of AT amidst possible confounding factors such as antibiotic use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Essential hypertension involves complex cardiovascular regulation. The autonomic nervous system function fluctuates throughout the sleep-wake cycle and changes with advancing age. However, the precise role of the autonomic nervous system in the development of hypertension during aging remains unclear. In this study, we characterized autonomic function during the sleep-wake cycle in different age groups with essential hypertension. This study included 97 men (53 with and 44 without hypertension) aged 30-79 years. They were stratified by age into young (< 40 years), middle-aged (40-59 years), and older (60-79 years) groups. Polysomnography and blood pressure data were recorded for 2 min before and during an hour-long nap. Autonomic function was assessed by measuring heart rate variability and blood pressure variability. Data were analyzed using t tests, correlation analyses, and two-way analysis of variance. During nonrapid eye movement (nREM), a main effect of age was observed on cardiac parasympathetic measures and baroreflex sensitivity (BRS), with the highest and lowest levels noted in the younger and older groups, respectively. The coefficients of the correlations between these measures and age were lower in patients with hypertension than in normotensive controls. The BRS of young patients with hypertension was similar to that of their middle-aged and older counterparts. However, cardiac sympathetic activity was significantly higher (p = 0.023) and BRS was significantly lower (p = 0.022) in the hypertension group than in the control group. During wakefulness, the results were similar although some of the above findings were absent. Autonomic imbalance, particularly impaired baroreflex, plays a more significant role in younger patients with hypertension. The nREM stage may be suitable for gaining insights into the relevant mechanisms., (© 2023. The Author(s).)

Objective: To identify the value of head rotation in the supine position and oral appliance (OA) use in drug-induced sleep endoscopy (DISE)., Study Design: Eighty-three sleep apnea adults undergoing target-controlled infusion-DISE (TCI-DISE) were recruited from a tertiary academic medical center., Setting: During DISE, 4 positions were utilized: supine position (position 1), head rotation (position 2), mandibular advancement using an OA (position 3), and head rotation with an OA (position 4)., Methods: Polysomnography (PSG) data and anthropometric variables during DISE were analyzed., Results: Eighty-three patients (65 men and 18 women; mean [standard deviation, SD], 48.5 [11.0] years) who underwent PSG and TCI-DISE were included. The mean (SD) apnea-hypopnea index (AHI) was 35.5 (22.4) events/h. Twenty-three patients had persistent complete concentric velopharyngeal collapse in the supine position, even with concurrent head rotation and OA (position 4). Their mean (SD) AHI was 54.7 (24.6) events/h, significantly higher than that of the 60 patients without such collapse in position 4 (p < .001). Their mean (SD) body mass index (BMI) was 29.0 (4.1) kg/m 2 , also significantly higher (p = .005). After adjustment for age, BMI, tonsil size, and tongue position, the degree of velum and tongue base obstruction was significantly associated with sleep apnea severity in positions 2, 3, and 4., Conclusion: We showed the feasibility, safety, and usefulness of using simple edge-to-edge, reusable OA in DISE. Patients who are not responsive to head rotation and OA during TCI-DISE may need upper airway surgery and/or weight control., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Particulate matter < 2.5 μm (PM2.5) exposure is associated with increased arrhythmia events and cardiovascular mortality, but the detailed mechanism remained elusive. In the current study, we aimed to investigate the autonomic alterations in a rodent model after acute exposure to PM2.5. Twelve male WKY rats were randomized to control and PM2.5 groups. All were treated with 2 exposures of oropharyngeal aerosol inhalations (1 μg PM2.5 per gram of body weight in 100 μL normal saline for the PM2.5 group) separately by 7 days. Polysomnography and electrocardiography were surgically installed 7 days before oropharyngeal inhalation and monitored for 7 days after each inhalation. Physiologic monitors were used to define active waking (AW), quiet sleep (QS), and paradoxical sleep (PS). Autonomic regulations were measured by heart rate variability (HRV). The protein expression of ventricular tissue of the 2 groups was compared at the end of the experiment. In sleep pattern analysis, QS interruption of the PM2.5 group was significantly higher than the control group (0.52 ± 0.13 events/min, 0.35 ± 0.10 events/min, p = 0.002). In HRV analysis, the LF/HF was significantly higher for the PM2.5 group than the control group (1.15 ± 0.16, 0.64± 0.30, p = 0.003), largely driven by LF/HF increase during the QS phase. Ionic channel protein expression from Western blots showed that the PM2.5 group had significantly lower L-type calcium channel and higher SERCA2 and rectifier potassium channel expressions than the control group, respectively. Our results showed that acute PM2.5 exposure leads to interruption of QS, sympathetic activation, and recruitment of compensatory calcium handling proteins. The autonomic and calcium dysregulations developed after PM 2.5 exposure may explain the risk of sleep disturbance and sleep-related arrhythmia., (© 2023. Springer Nature Limited.)

Occurrence of amyloid-β (Aβ) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep-wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aβ levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aβ aggregation but without significant differences in cognitive performance had frequent sleep-wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection., (© 2023. The Author(s).)

Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution., Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models., Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1., Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chuang, Lin, Hsu, Chuang, Li, Fang, Huang, Yang, Lee, Kuo, Yang and Lee.)

Background: Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined., Methods: This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA., Results: Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: β = 16.672, standard error = 8.274, p = 0.048)., Conclusion: These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Purpose: This study aimed to investigate (1) the role of mouth puffing phenomenon and upper airway features in obstructive sleep apnea (OSA) and (2) whether mouth-taping during sleep alleviated the severity of OSA., Participants and Methods: Seventy-one participants underwent a two-night home sleep test (the first day sleeping normally; the second day sleeping with their mouths being taped); their oximetry desaturation index (ODI) and mouth puffing signals (non-mouth puffing, complete mouth puffing, intermittent mouth puffing (IMP), and side mouth puffing) were detected by a validated fingertip pulse oximeter and a mouth puffing detector. The participants were grouped into the ODI-improved group and the ODI-not-improved group according to their sleeping test results. The radiograph was taken by cone-beam computed tomography and cephalometries. Upper airway features including airways, soft tissues, and oral cavity variables were measured., Results: Participants with severe OSA showed a higher IMP percentage compared with those with normal, mild, and moderate OSA (severe: 33.78%, moderate: 22.38%, mild: 14.55%, normal: 0.31%, p < 0.001). In all participants, the ODI and the percentage of SpO 2 under 90 (T90) were positively related to body mass index (BMI) (r = 0.310 and 0.333, respectively), while ODI and T90 were negatively correlated with the minimum width of the airway (r = -0.473 and -0.474, respectively); all mentioned relationships were significant (p < 0.05)., Conclusion: IMP proportions were found to be higher in the half of participants whose ODI did not improve after mouth-taping and in those with severe OSA. Moreover, OSA patients with higher ODI, higher T90, and higher proportions of IMP were more likely to have a narrower upper airway., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Jau et al.)

Exposure to bright morning light (BML) entrains the master circadian clock, modulates physiological circadian rhythms, and reduces sleep-wake disturbances. However, its impact on the autonomic nervous system at night remains unclear. Here, we investigated the effects of BML exposure on parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) activity at night in elderly women. This nonrandomized controlled pilot study included female participants aged ≥ 60 years who were diagnosed with a type of dementia or cognitive disorder, excluding individuals with pacemakers. The treatment group was exposed to 2500 lx of BML, whereas the control group was exposed to 200 lx of general lighting. We measured heart rate variability to quantify ANS activity. The treatment group displayed significant increases in high-frequency (HF) power (Roy's largest root = 1.62; p < 0.001) and nonsignificant decreases in normalized low-frequency (LF%) power. The corresponding nonsignificant decreases in the low-frequency/high-frequency (LF/HF) ratio and cognitive function were correlated with PSNS activity (Roy's largest root = 1.41; p < 0.001), which improved severe dementia. BML exposure reduced SNS activity and enhanced PSNS activity at night in female participants, which improved cognitive function. Thus, BML therapy may be a useful clinical tool for alleviating cognitive decline.

Aging causes brain function degeneration and slows many motor and behavioural responses. The hippocampal theta rhythm (4-12 Hz) is related to cognition and locomotion. However, the findings on aging-related changes in the frequency and amplitude of hippocampal theta oscillations have been inconsistent. We hypothesized that older rats have slower responses in terms of hippocampal theta rhythm during voluntary wheel running than do young adult rats. By simultaneously recording electroencephalography and physical activity (PA), we evaluated theta oscillations in 8-week-old (young adult) and 60-week-old (middle-aged) rats before and during wheel running, which was conducted only during the rats' 12-h dark period. To test the alterations of hippocampal theta rhythm in voluntary wheel running, we analyzed the signals without (8-s) or with (2-s) chronological order. No significant difference was observed in total frequency (TP, 4-12 Hz), low-frequency (LT, 4-6.5 Hz), or high-frequency (9.5-12 Hz) theta activity between active waking and overall running in either group. The theta oscillations were slower in the middle-aged rats than in the young adult rats during wheel running but increased during running for both age groups. During wheel running, the middle-aged rats exhibited an increased LT, which was related to PA. On the basis of the chronological order of running, the young adult rats exhibited increased TP, and the middle-aged rats exhibited significant increases in middle-frequency (MT, 6.5-9.5 Hz) theta activity. The dominant modulations of MT in the middle-aged rats may have caused nonsignificant changes in total activity. These between-group differences in theta rhythm characteristics during voluntary running provide insights into age-related brain function decline., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: This study aimed to design a device to monitor mouth puffing phenomena of patients with obstructive sleep apnea when mouth-taped and to employ video recording and computing algorithms to double-check and verify the efficacy of the device., Methods: A mouth puffing detector (MPD) was developed, and a video camera was set to record the patients' mouth puffing phenomena in order to make ensure the data obtained from the device was appropriate and valid. Ten patients were recruited and had polysomnography. A program written in Python was used to investigate the efficacy of the program's algorithms and the relationship between variables in polysomnography (sleep stage, apnea-hypopnea index or AHI, oxygen-related variables) and mouth puffing signals (MPSs). The video recording was used to validate the program. Bland-Altman plot, correlations, independent sample t-test, and ANOVA were analyzed by SPSS 24.0., Results: Patients were found to mouth puff when they sleep with their mouths taped. An MPD was able to detect the signals of mouth puffing. Mouth puffing signals were noted and categorized into four types of MPSs by our algorithms. MPSs were found to be significantly related to relative OSA indices. When all participants' data were divided into minutes, intermittent mouth puffing (IMP) was found to be significantly different from non-mouth puffing in AHI, oxygen desaturation index (ODI), and time of oxygen saturation under 90% (T90) (AHI: 0.75 vs. 0.31; ODI: 0.75 vs. 0.30; T90: 5.52 vs. 1.25; p < 0.001). Participants with severe OSA showed a higher IMP percentage compared to participants with mild to moderate OSA and the control group (severe: 38%, mild-to-moderate: 65%, control: 95%; p < 0.001)., Conclusions: This study established a simple way to detect mouth puffing phenomena when patients were mouth-taped during sleep, and the signals were classified into four types of MPSs. We propose that MPSs obtained from patients wearing the MPD can be used as a complement for clinicians to evaluate OSA., (© 2022. The Author(s).)

Background: Obstructive sleep apnea (OSA) is associated with impaired sleep quality and autonomic dysfunction. Adenotonsillectomy significantly improves subjective and objective sleep quality in children with OSA. However, the postoperative changes in heart rate variability (HRV) indices (indicators of cardiac autonomic function) and their importance remain inconclusive in childhood OSA. This retrospective case series aimed to investigate the association of sleep HRV indices, total OSA-18 questionnaire score (a subjective indicator of sleep quality) and polysomnographic parameters (objective indicators of sleep quality), and effects of adenotonsillectomy on HRV indices, total OSA-18 questionnaire score and polysomnographic parameters in children with OSA., Methods: Seventy-six children with OSA were included in baseline analysis, of whom 64 (84%) completed at least 3 months follow-up examinations after adenotonsillectomy and were included in outcome analysis. Associations between baseline variables, and relationships with treatment-related changes were examined., Results: Multivariable linear regression models in the baseline analysis revealed independent relationships between tonsil size and obstructive apnea-hypopnea index (OAHI), adenoidal-nasopharyngeal ratio and very low frequency (VLF) power of HRV (an indicator of sympathetic activity), and normalized low frequency power (an indicator of sympathetic activity) and OAHI. The outcome analysis showed that adenotonsillectomy significantly improved standard deviation of all normal-to-normal intervals, and high frequency power, QoL (in terms of reduced total OSA-18 questionnaire score), OAHI and hypoxemia. Using a conceptual serial multiple mediation model, % change in OSA-18 questionnaire score and % change in VLF power serially mediated the relationships between change in tonsil size and % change in OAHI., Conclusions: The improvement in OAHI after adenotonsillectomy was serially mediated by reductions in total OSA-18 questionnaire score and VLF power. These preliminary findings are novel and provide a direction for future research to investigate the effects of VLF power-guided interventions on childhood OSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Chuang, Hsieh, Wang, Chuang, Li, Fang, Huang, Lee, Yang, Kuo and Yang.)

Background: Attention deficit hyperactivity disorder (ADHD) is a well-studied topic in child and adolescent psychiatry. ADHD diagnosis relies on information from an assessment scale used by teachers and parents and psychological assessment by physicians; however, the assessment results can be inconsistent., Purpose: To construct models that automatically distinguish between children with predominantly inattentive-type ADHD (ADHD-I), with combined-type ADHD (ADHD-C), and without ADHD., Methods: Clinical records with age 6-17 years-old, for January 2011-September 2020 were collected from local general hospitals in northern Taiwan; the data were based on the SNAP-IV scale, the second and third editions of Conners' Continuous Performance Test (CPT), and various intelligence tests. This study used an artificial neural network to construct the models. In addition, k -fold cross-validation was applied to ensure the consistency of the machine learning results., Results: We collected 328 records using CPT-3 and 239 records using CPT-2. With regard to distinguishing between ADHD-I and ADHD-C, a combination of demographic information, SNAP-IV scale results, and CPT-2 results yielded overall accuracies of 88.75 and 85.56% in the training and testing sets, respectively. The replacement of CPT-2 with CPT-3 results in this model yielded an overall accuracy of 90.46% in the training set and 89.44% in the testing set. With regard to distinguishing between ADHD-I, ADHD-C, and the absence of ADHD, a combination of demographic information, SNAP-IV scale results, and CPT-2 results yielded overall accuracies of 86.74 and 77.43% in the training and testing sets, respectively., Conclusion: This proposed model distinguished between the ADHD-I and ADHD-C groups with 85-90% accuracy, and it distinguished between the ADHD-I, ADHD-C, and control groups with 77-86% accuracy. The machine learning model helps clinicians identify patients with ADHD in a timely manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Chang, Huang, Kuo and Chiu.)

Objective: Generalized anxiety disorder (GAD) and sleep-disordered breathing (SDB) share similar symptoms, such as poor sleep quality, irritability, and poor concentration during daily activities. This study aims to investigate the proportion of undiagnosed SDB and its impacts on anxiety severity and autonomic function in newly diagnosed, sedative-free GAD patients., Methods: This prospective case-control study included newly diagnosed GAD patients and control participants with matched age, sex, and body mass index (BMI) in Taiwan. All participants completed questionnaires for sleep and mood symptoms and a resting 5-min heart rate variability (HRV) examination during enrollment. The participants also used a home sleep apnea test to detect SDB. An oxygen desaturation index (ODI) ≥ 5 was considered indicative of SDB., Results: In total, 56 controls and 47 newly diagnosed GAD participants (mean age 55.31 ± 12.36 years, mean BMI 23.41 ± 3.42 kg/m 2 ) were included. There was no significant difference in the proportion of undiagnosed SDB in the control and sedative-free GAD groups (46.43 vs. 51.06%). Sedative-free GAD patients with SDB scored significantly higher on Beck Anxiety Inventory (23.83 ± 11.54) than those without SDB (16.52 ± 10.61) ( p < 0.001). Both control and sedative-free GAD groups with SDB had worse global autonomic function than the control group without SDB, as evidenced by the HRV results ( p < 0.05 for all)., Conclusion: Average age 55 years and mean BMI 23 kg/m 2 patients with GAD and matched controls had an undiagnosed SDB prevalence of approximately 50%. SDB correlated with worsening anxiety severity and reduced cardiac autonomic function. Moreover, age and BMI were considered major risk factors for predicting undiagnosed SDB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Kung, Lai, Lee, Jen, Chang, Liu, Kuo and Yang.)

Objective: Sleep apnea (SA) is characterized by intermittent hypoxia (IH), which increases sympathetic activity and sleep fragmentation, thus increasing the risk of stroke. SA is a highly prevalent disease and can worsen prognosis in patients with stroke. However, the correlation of changes in the cardiac autonomic nervous system and sleep patterns under IH with sensorimotor behavior and cerebral infarction after stroke remains unclear. We hypothesized that dysregulated autonomic activity and unstable sleep patterns induced by IH and correlated with cerebral infarction and abnormal sensorimotor behavior after middle cerebral artery occlusion (MCAO)., Methods: Wistar-Kyoto rats (WKY) were divided into IH (hypoxia: 5 % O 2, 8 h/day) and RA group (room air) for 2 weeks and both groups were subjected to MCAO. After MCAO, the IH group was continuously exposed to IH for 1 week. The 24-h physiological signals, blood pressure, and sensorimotor behavior were recorded at baseline (Bas), the first and second weeks during IH (RA/IH1W and RA/IH2W, respectively), and poststroke., Results: Before MCAO, IH caused sympathetic activity during sleep and parasympathetic activity of active waking (AW) to increase. Moreover, IH reduced the accumulated time and duration of paradoxical sleep (PS) and increased the interruption during sleep. After MCAO, IH increased blood pressure, more severe brain damage, and poor sensorimotor performance. Moreover, IH reduced autonomic activity after MCAO and decreased sympathetic activity was associated with poor sensorimotor performance., Conclusion: Autonomic activity and sleep patterns affected by IH were correlated with increased cerebral infarction and poor sensorimotor behavior after MCAO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Before caring for patients, video instruction is commonly used for undergraduate medical students, and 360° virtual reality (VR) videos have gained increasing interest in clinical medical education. Therefore, the effect of immersive 360° VR video learning compared with two-dimensional (2D) VR video learning in clinical skills acquisition should be evaluated. This randomized, intervention-controlled clinical trial was aimed to assess whether immersive 360° VR video improves undergraduate medical students' learning effectiveness and reduces the cognitive load in history taking and physical examination (H&P) training. From May 1 2018 to October 30 2018, 64 senior undergraduate medical students in a tertiary academic hospital were randomized to receive a 10-min immersive 360° (360° VR video group; n  = 32) or 2D VR instructional video (2D VR video group; n  = 32), including essential knowledge and competency of H&P. The demographic characteristics of the two groups were comparable for age, sex, and cognitive style. The total procedure skill score, physical examination score, learner's satisfaction score, and total cognitive load in the 360° VR video group were significantly higher than those in the 2D VR video group (effect sizes [95% confidence interval]: 0.72 [0.21-1.22], 0.63 [0.12-1.13], 0.56 [0.06-1.06], and 0.53 [0.03-1.03], respectively). This study suggested that a10-minute 360° VR video instruction helped undergraduate medical students perform fundamental H&P skills as effectively as 2D VR video. Furthermore, the 360° VR video might result in significantly better procedural metrics of physical examinations with higher learner satisfaction despite the higher cognitive load., Supplementary Information: The online version contains supplementary material available at 10.1007/s10055-022-00664-0., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare., (© The Author(s) 2022.)

Cardiovascular function is related to age, sex, and state of consciousness. We hypothesized that cardiovagal baroreflex sensitivity (BRS) demonstrates different patterns in both sexes before and after 50 years of age and that these patterns are associated with patterned changes during the sleep-wake cycle. We recruited 67 healthy participants (aged 20-79 years; 41 women) and divided them into four age groups: 20-29, 30-49, 50-69, and 70-79 years. All the participants underwent polysomnography and blood pressure measurements. For each participant, we used the average of the arterial pressure variability, heart rate variability (HRV), and BRS parameters during the sleep-wake stages. BRS and HRV parameters were significantly negatively correlated with age. The BRS indexes were significantly lower in the participants aged ≥ 50 years than in those aged < 50 years, and these age-related declines were more apparent during non-rapid eye movement sleep than during wakefulness. Only BRS demonstrated a significantly negative correlation with age in participants ≥ 50 years old. Women exhibited a stronger association than men between BRS and age and an earlier decline in BRS. Changes in BRS varied with age, sex, and consciousness state, each demonstrating a specific pattern. The age of 50 years appeared to be a crucial turning point for sexual dimorphism in BRS. Baroreflex modulation of the cardiovascular system during sleep sensitively delineated the age- and sex-dependent BRS patterns, highlighting the clinical importance of our results. Our findings may aid in screening for neurocardiac abnormalities in apparently healthy individuals., (© 2022. The Author(s).)

Background: The diagnosis of acute mountain sickness, which lacks a reliable and objective diagnostic tool, still depends on the clinical symptoms and signs and remains a major threat and unpredictable disease affecting millions of mountaineers., Objectives: To record electroencephalography signals with small, convenient, wireless equipment and to test whether electroencephalography parameters, which are more sensitive and reliable markers, could predict the symptoms of acute mountain sickness., Methods: Twenty-five participants were enrolled and separated into two groups to climb Mount Jade in Taiwan. We collected electrocardiography signals and arterial oxygen saturation data at ground, moderate (2,400 m), and high altitude (3,400 m). A spectral analysis of the electrocardiography was performed to assess the study subjects' electroencephalography activity at different frequencies (α, β, θ, δ) and the mean power frequency of electrocardiography. The clinical symptoms and Lake Louise Acute Mountain Sickness scores of the subjects were recorded for comparison., Results: A significant change in the δ power of electroencephalography was recorded in subjects ascending from the ground to a high altitude of 3,400 m in a 4-day itinerary. In addition, between the two groups of subjects with and without acute mountain sickness (Lake Louise Acute Mountain Sickness scores < 3 and ≥ 3), the δ power of electroencephalography at the fronto-parietal 1 and parietal 3 electrodes at moderate altitude as well as the changes of δ power and mean power frequency of electrocardiography over parietal 4 at high altitude showed a significant difference. At moderate altitude, the increasing δ power of electroencephalography at the parietal 4 electrode was related to the headache symptom of acute mountain sickness before ascending to high altitude., Conclusion: At moderate altitude, the δ power increase of electroencephalography at the P4 electrode could be a predictor of acute mountain sickness symptoms before ascending to high altitude. Thus, electroencephalography had the potential to identify the risk of acute mountain sickness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Virtual reality (VR) applications could be beneficial for education, training, and treatment. However, VR may induce symptoms of simulator sickness (SS) such as difficulty focusing, difficulty concentrating, or dizziness that could impair autonomic nervous system function, affect mental workload, and worsen interventional outcomes. In the original randomized controlled trial, which explored the effectiveness of using a 360° VR video versus a two-dimensional VR video to learn history taking and physical examination skills, only the former group participants had SS. Therefore, 28 undergraduate medical students who participated in a 360° VR learning module were included in this post hoc study using a repeated measures design. Data of the Simulator Sickness Questionnaire (SSQ), heart rate variability (HRV) analysis, Task Load Index, and Mini-Clinical Evaluation Exercise were retrospectively reviewed and statistically analyzed. Ten (36%) participants had mild SS (total score > 0 and ≤ 20), and 18 (64%) had no SS symptom. Total SSQ score was positively related to the very low frequency (VLF) band power, physical demand subscale, and frustration subscale, and inversely related to physical examination score. Using multilevel modeling, the VLF power mediated the relationship between total SSQ score and physical examination score. Furthermore, frustration subscale moderated the mediating effects of the VLF power. Our results highlight the importance of documenting SS to evaluate a 360° VR training program. Furthermore, the combination of HRV analysis with mental workload measurement and outcome assessments provided the important clinical value in evaluating the effects of SS in VR applications in medical education., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare., (© The Author(s) 2022.)

Autonomic dysfunction and sleep problems are closely associated with hypertension and predict cardiovascular morbidity and mortality. Animal studies and clinical observations have identified exercise as an important factor in preventing and treating hypertension. However, the roles of autonomic function and sleep in the antihypertensive mechanisms of exercise are still not fully understood. This study aimed to clarify the physiological mechanisms associated with autonomic function and sleep through wheel exercise. Male spontaneously hypertensive rats (SHRs) were grouped into a wheel-exercised group and a sedentary group (controls). Electroencephalogram, electromyogram, electrocardiogram, and mean arterial pressure (MAP) were recorded simultaneously for 24 h once a week over 11 weeks. Wheel exercise was initiated in the SHRs at 12 weeks old and continued for another eight weeks. A significant suppression in the age-related elevation of MAP was noted in the SHRs undergoing wheel exercise. The reduction in MAP was correlated with increased parasympathetic activity and baroreflex sensitivity and decreased sympathetic activity, mainly during quiet sleep. Exercise increased the paradoxical sleep time and theta power (associated with cognitive function) but not the delta power (an indicator of sleep depth) or the attenuation of circadian rhythm flattening (characterized by increased wakefulness and less sleep during the light period and the opposite during the dark period). Furthermore, the exercise-induced changes in autonomic function occurred before those in sleep patterns, which were dependent on each other. In conclusion, wheel exercise can modulate sleep-related cardiovascular dysfunction and the flattening of circadian rhythm, preventing the progression of hypertension, which reduces the incidence of cardiovascular diseases., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

It is known that anxiety has a lot of comorbidity such as depression and may cause older subjects to be more prone to anxiety. Animal studies have also observed that older rats have lower movement in different situations, somewhat like anxiety symptoms (avoidance and freezing). The anxiety level of rodents is commonly evaluated using the elevated plus maze test, and videos are often used to record and quantify the activities of animals during the test. Furthermore, aging can reduce the frequency and activity of locomotion-induced hippocampal theta rhythm, and these reductions are also reflected in sensory-motor integration and cognition. Thus, directly analyzing the hippocampal theta rhythm and the quantity and quality of physical activity (PA) during the anxiety test can help elucidate the mechanisms underlying the anxiety-like behaviour. We explored alterations in the hippocampal theta rhythm, PA, and behavioural consistency (cross-correlation with 8-s window length) from triaxial acceleration vectors and subsequently examined the effects of age during the elevated plus maze test. We hypothesized that middle-aged rats would exhibit more anxiety, which is correlated with a reduction in behavioural consistency and hippocampal theta frequency during the elevated plus maze test. The middle-aged rats had a lower open-arm frequency and more low-frequency theta oscillations. The middle-aged rats had a lower mean power frequency (Frq) of the hippocampal theta rhythm, PA, and behavioural consistency. The Frq of the middle-aged rats was positively correlated with behavioural consistency. The results indicated that behavioural consistency could distinguish age-related anxiety-like behaviour. Behavioural consistency can serve as an index for the quality of movement and be used to distinguish age-related anxiety., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Autonomic neural controls in sleep regulation have been previously demonstrated; however, whether these alternations can be observed by different sleep staging approaches remains unclear. Two established methods for sleep staging-the standardized visual scoring and the cardiopulmonary coupling (CPC) analysis based on electrocardiogram-were used to explore the cardiovascular profiles of sleep., Methods: Overnight polysomnography was recorded together with continuous beat-to-beat blood pressure. Cortical activity, heart rate variability, blood pressure variability, and baroreflex sensitivity during sleep stages from 24 nights of sleep were obtained from 15 normotensive participants and analyzed., Results: Non-rapid eye movement sleep (NREM) from visual scoring and restful sleep (RS) of CPC both showed the highest delta power of electroencephalogram (EEG) and lowest beta activity of EEG in comparison with other sleep stages (p < .001); likewise, the lowest total power of heart rate variability and suppressed vascular-sympathetic activity, reflected by low-frequency power of blood pressure variability, as well as a trend in elevated baroreflex sensitivity, were observed in the NREM or RS. This suppressed vascular-sympathetic activity during stable sleep further exhibited a significant correlation with increased slow-wave activity (NREM: r = -0.292 ± 0.34, p = .002; RS: r = -0.209 ± 0.30, p = .010)., Conclusions: Autonomic nervous system is evidently associated with stable sleep, as indicated by the similar findings obtained from sleep stages categorized by standardized visual scoring or CPC analysis. Such association between cardiovascular neural activity and sleep EEGs can be observed regardless of the sleep staging approach followed., (Copyright © 2022 by the American Psychosomatic Society.)

Aim: The aim of this study was to examine the association between anxiety disorders and obstructive sleep apnea (OSA)., Methods: This is a population-based, retrospective case-control study using Taiwan's nationwide database. We included patients with OSA aged ≥12 years, diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 327 and 780. Each enrolled patient with OSA needed to undergo a polysomnography examination within 1 year pre- or post-OSA occurrence. Patients with OSA and controls were selected in a 1:4 ratio. Patients with anxiety disorders (ICD-9-CM code 300) were diagnosed by board-certified psychiatrists and required to visit the outpatient clinic at least three times per year. Multivariate logistic regression and interaction analyses were used to evaluate the objective association., Results: This study enrolled 7987 and 31 948 participants with and without OSA, respectively. A significant difference in anxiety exposure was observed only pre-OSA diagnosis but not post-OSA diagnosis. Compared with patients without anxiety disorders: (i) those with anxiety disorders had an adjusted odds ratio (aOR) of ≈1.864 in OSA comorbidity (aOR = 1.864; 95% confidence interval [CI] = 1.337-2.405); and (ii) subgroup analysis showed a significant interaction that anxiety patients of male sex, aged 18 to 44 years, aged 45 to 64 years, and hypertension had a higher aOR in OSA comorbidity (aOR = 2.104 [95% CI = 1.436-2.589], aOR = 1.942 [95% CI = 1.390-2.503], aOR = 2.179 [95% CI = 1.564-2.811], and aOR = 2.092 [95% CI = 1.497-2.706], respectively)., Conclusion: The study revealed a higher ratio of previous anxiety exposure in patients with OSA. Compared with those without anxiety, anxiety patients of male sex, aged 18 to 64 years, and with hypertension had a higher risk of OSA comorbidity., (© 2022 The Authors. Psychiatry and Clinical Neurosciences © 2022 Japanese Society of Psychiatry and Neurology.)

Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Sympathetic hyperactivity and poor sleep quality have been reported in patients with myocardial infarction (MI). Sleep is an important modulator of cardiovascular function. We aimed to evaluate the effects of renal denervation (RDN) on cardiac autonomic activity and disordered sleep patterns in rats with MI., Methods: Wireless transmission of polysomnographic recordings was performed in sham and left coronary artery (LCA) ligation male rats during normal daytime sleep before and after RDN. Spectral analyses of electroencephalogram and electromyogram (EMG) recordings were performed to define active waking, quiet sleep, and paradoxical sleep. Cardiac autonomic activity was measured by analyzing the power spectrum of heart rate variability. Central sleep apnea events were measured by analyzing the EMG recordings of the diaphragm., Results: In the LCA ligation group, there was a higher low-frequency (LF)/high-frequency (HF) power ratio during sleep; the LF/HF ratio decreased significantly in the rats that underwent RDN in all sleep stages when compared with that in the rats that did not. The frequency of sleep interruptions increased without RDN in the LCA ligation group when compared with that in the sham group. This change was ameliorated and prevented with RDN in the LCA ligation group., Conclusions: Our results demonstrate significant sleep fragmentation with sympathetic hyperactivity after MI and that RDN prevents autonomic dysfunction and disordered sleep. RDN may then reduce sleep apnea and sleep-related sudden cardiac death after MI by restoring autonomic homeostasis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Many studies have reported that the production of Lactobacillus brevis is beneficial for sleep, but the underlying mechanism remains unclear. Other known beneficial effects of Lactobacillus brevis include improvement of anxious or depressive symptoms and better modulation of the autonomic nervous system, both of which impact sleep. In this study, we investigated whether the sleep benefit of Lactobacillus brevis was associated with the modulating effects on the autonomic nervous system and anxious/depressive symptoms., Main Methods: Wistar-Kyoto rats were fed the production of Lactobacillus brevis (ProGA28) for the last 2 weeks of treatment before being exposed to case exchange (stress-induced insomnia paradigm). Waking, quiet sleep, and paradoxical sleep states were defined based on polysomnographic measurements. Autonomic functioning was assessed by heart rate variability (HRV). A combined behavioral test was used to evaluate anxiety-like or depressive-like behaviors after the following 2 days., Key Findings: In exposure to the dirty cage, the control group had significant prolongation of sleep latency, sleep loss during the first 2 h, and decreased parasympathetic activity and increased sympathetic activity during quiet sleep, which were significantly mitigated in the ProGA28 group. In behavioral tests, the ProGA28 group exhibited significantly less anxiety/depression-like motor responses in the elevated plus maze test, the forced swimming test, and the three-chamber social interaction test. Less initial sleep loss in the ProGA28 group was related to higher parasympathetic activity during quiet sleep, and shorter sleep latency in both groups was associated with longer time staying in the open arm in the elevated plus maze test., Significance: These findings suggest that L. brevis ProGA28 can attenuate stress-related sleep disturbance, which may be associated with increased parasympathetic activity and decreased anxiety-like behaviors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Learning through a 360° virtual reality (VR) or 2D video represents an alternative way to learn a complex medical education task. However, there is currently no consensus on how best to assess the effects of different learning materials on cognitive load estimates, heart rate variability (HRV), outcomes, and experience in learning history taking and physical examination (H&P) skills., Objective: The aim of this study was to investigate how learning materials (ie, VR or 2D video) impact learning outcomes and experience through changes in cognitive load estimates and HRV for learning H&P skills., Methods: This pilot system-design study included 32 undergraduate medical students at an academic teaching hospital. The students were randomly assigned, with a 1:1 allocation, to a 360° VR video group or a 2D video group, matched by age, sex, and cognitive style. The contents of both videos were different with regard to visual angle and self-determination. Learning outcomes were evaluated using the Milestone reporting form. Subjective and objective cognitive loads were estimated using the Paas Cognitive Load Scale, the National Aeronautics and Space Administration Task Load Index, and secondary-task reaction time. Cardiac autonomic function was assessed using HRV measurements. Learning experience was assessed using the AttrakDiff2 questionnaire and qualitative feedback. Statistical significance was accepted at a two-sided P value of <.01., Results: All 32 participants received the intended intervention. The sample consisted of 20 (63%) males and 12 (38%) females, with a median age of 24 (IQR 23-25) years. The 360° VR video group seemed to have a higher Milestone level than the 2D video group (P=.04). The reaction time at the 10th minute in the 360° VR video group was significantly higher than that in the 2D video group (P<.001). Multiple logistic regression models of the overall cohort showed that the 360° VR video module was independently and positively associated with a reaction time at the 10th minute of ≥3.6 seconds (exp B=18.8, 95% CI 3.2-110.8; P=.001) and a Milestone level of ≥3 (exp B=15.0, 95% CI 2.3-99.6; P=.005). However, a reaction time at the 10th minute of ≥3.6 seconds was not related to a Milestone level of ≥3. A low-frequency to high-frequency ratio between the 5th and 10th minute of ≥1.43 seemed to be inversely associated with a hedonic stimulation score of ≥2.0 (exp B=0.14, 95% CI 0.03-0.68; P=.015) after adjusting for video module. The main qualitative feedback indicated that the 360° VR video module was fun but caused mild dizziness, whereas the 2D video module was easy to follow but tedious., Conclusions: Our preliminary results showed that 360° VR video learning may be associated with a better Milestone level than 2D video learning, and that this did not seem to be related to cognitive load estimates or HRV indexes in the novice learners. Of note, an increase in sympathovagal balance may have been associated with a lower hedonic stimulation score, which may have met the learners' needs and prompted learning through the different video modules., Trial Registration: ClinicalTrials.gov NCT03501641; https://clinicaltrials.gov/ct2/show/NCT03501641., (©Yi-Ping Chao, Hai-Hua Chuang, Li-Jen Hsin, Chung-Jan Kang, Tuan-Jen Fang, Hsueh-Yu Li, Chung-Guei Huang, Terry B J Kuo, Cheryl C H Yang, Hsin-Yih Shyu, Shu-Ling Wang, Liang-Yu Shyu, Li-Ang Lee. Originally published in JMIR Serious Games (https://games.jmir.org), 22.11.2021.)