A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action.

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

[Sleep-Disordered Breathing at High Altitude: Its Characteristics and Research Progress in Treatment].

Hypobaric hypoxia in regions of high altitude may increase the risk of having sleep-disordered breathing (SDB). SDB at high altitude mainly refers to the SDB incurred in highlanders and lowlanders at a high altitude. At present, research on SDB at high altitude is mainly focused on these two groups of people. On the one hand, highlanders have SDB at a higher prevalence and greater severity than lowlanders do and highlanders have a prolonged duration of apnea when they travel to low-altitude regions. On the other hand, the severity of SDB increased in lowlanders when they travel to high altitude, represented mainly by an increase in central and hypopnea events. In terms of treatment, a substantial number of studies have shown that medication, including acetazolamide and dexamethasone, and nocturnal oxygen supplementation could improve SDB in lowlanders when they travel to high altitude. However, not much research has been done on the treatment of SDB in highlanders and it has only been reported that nocturnal oxygen supplementation was an available treatment option. Herein, we summarized the latest research findings on SDB at high altitude, providing the basis for further studies about the characteristics and treatments for highlanders with SDB.

[Current Status of and Progress in Research on Obstructive Sleep Apnea and Comorbid Depressive Disorders].

Obstructive sleep apnea (OSA) and depressive disorders are common diseases in adults and they share in common many clinical symptoms, including sleep disturbance, fatigue, lack of concentration and cognitive function impairment. OSA and depressive disorders also share some common pathophysiological changes, including increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, chronic low-grade inflammation, oxidative stress, and changes in gut microbiota and neurotransmitters, which may contribute to the comorbidity of OSA and depressive disorders. In the case of comorbid OSA and depressive disorders, OSA and depressive disorders may affect and exacerbate each other, thereby increasing the severity of diseases, entailing greater risk of cardiovascular and metabolic diseases, and causing greater difficulty in treatment. Herein, we summarized the latest research findings on the epidemiology, possible mechanisms, harms, and treatment of comorbid OSA and depressive disorders. This review may help improve clinicians' understanding of the comorbidity of OSA and depression disorders, thereby promoting early screening, prompt diagnosis and treatment, and improved prognosis. Further studies are needed for better understanding of the effect of the comorbidity of OSA and depressive disorders and treatment on cardiometabolic diseases.

[Guideline for the Standardized Construction of Sleep Medicine Centers in China: Undertaking the Mission of Medicine of the Era and Caring for People's Sleep Health].

Humans spend one third of their life sleeping. Sleep, a vital life process, is an essential part of human health. In response to people's growing needs concerning sleep health, sleep medicine was born and is growing rapidly, and there is also an upsurge in the construction of sleep medicine centers in China and other countries. Unfortunately, there are no Chinese standards available for the construction of sleep medicine centers and the sleep medicine centers already constructed are of varied quality. In view of this academic problem, Professor Lu Lin, an academician of Chinese Academy of Sciences and the president of Peking University Sixth Hospital, organized Chinese experts with outstanding achievements in the field of sleep medicine to draft "Guideline for the Standardized Construction of Sleep Medicine Centers in China". This guideline mainly introduces the overall status of standardized construction of sleep medicine centers and the status of the construction of specialized sleep medicine centers in China, aiming to guide the construction of high-quality and high-standard sleep medicine centers in China, to promote the development of sleep medicine, and to safeguard people's sleep health.

[Clinical Characteristics of Obstructive Sleep Apnea and Comorbid Primary Aldosteronism].

Objective: To explore the characteristics of patients with obstructive sleep apnea (OSA) and comorbid primary aldosteronism (PA) and to explore the relevant factors affecting plasma aldosterone concentration. Methods: A total of 105 patients diagnosed with PA and admitted at West China Hospital, Sichuan University between January 2016 and December 2021 were retrospectively analyzed. The subjects were divided into a PA with comorbid snoring group (n=20) and a PA with comorbid OSA group (n=85) based on the results of polysomnography (PSG). The PA with comorbid OSA group was further divided into mild, moderate, and severe subgroups according to the apnea-hypopnea index (AHI). A total of 85 outpatients diagnosed with OSA were included as the control group. Demographic, clinical, biochemical, and PSG data were compared between the groups. Results: Compared with patients with only OSA, a significantly higher proportion of patients with OSA and comorbid PA had hypertension and elevated levels of systolic and diastolic blood pressure (P<0.05). In addition, patients with OSA and comorbid PA had significantly increased AHI and significantly decreased mean oxygen saturation and sleep efficiency (P<0.05). The more severe the OSA was, the higher levels of BMI, cholesterol, low-density lipoprotein, and uric acid the PA patients had. Linear regression analysis showed that the lowest oxygen saturation (ß=－0.222, P=0.045) was negatively correlated with plasma aldosterone concentration. Conclusion: Comorbidity with PA can aggravate the clinical manifestations of OSA, while OSA further disrupted the metabolism of lipids and uric acid in PA patients. Plasma aldosterone concentrations in patients with comorbid OSA and PA were affected by the lowest oxygen saturation level.

[Research Status of and Recommendations for Prevention and Control of Sleep Disorders in China].

The quality of sleep, a key physiological factor that regulates information, memory, decision making, and other vital brain functions, can affect important physiological functions of the human body. According to disease classification systems, sleep disorders can be categorized into more than 90 types, including sleep apnea, insomnia, and hypersomnia. It may cause a variety of adverse consequences, such as depression, anxiety and other emotional disorders, as well as physical diseases such as hypertension, diabetes and stroke. In addition, the relevant cardiovascular and cerebrovascular diseases and cognitive impairment not only harm physical health, but also are associated with workplace accidents and safety problems, constituting public safety hazards. Sleep disorders have become a major social and scientific problem that impacts on the national economy and the livelihood of the people. Research on sleep disorders should be given more attention by researchers and policy makers. Herein, we mainly discussed the latest findings and difficulties concerning research on the prevention and intervention of sleep disorders and proposed strategies and suggestions accordingly.

[Effect of Objective Daytime Sleepiness on Heart Rate Variability in Patients With Obstructive Sleep Apnea].

Objective: Excessive daytime sleepiness (EDS) is associated with cardiovascular events in patients with obstructive sleep apnea (OSA). Our study explored the correlation between objective daytime sleepiness assessed with daytime multiple sleep latency tests (MSLT) and heart rate variability (HRV) in OSA patients. The results may provide insight into possible mechanisms underlying increased risk of cardiovascular events in patients with OSA. Methods: A retrospective analysis was conducted with the data of 139 patients with OSA and 35 patients with primary snoring. All subjects underwent polysomnography (PSG) and MSLT at West China Hospital between January 2019 and May 2022. We used mean sleep latency (MSL) to measure the severity of EDS and to categorize OSA patients into three groups, severe EDS, light EDS, and non-EDS, with MSL of less than 5 minutes, 5 to 10 minutes, and greater than 10 minutes as the respective defining criteria for classification. A comparison of sleep structure, clinical characteristics, and HRV parameters was performed in order to evaluate the difference between OSA subgroups with varying levels of objective EDS and the primary snoring group. In addition, we also analyzed the correlation between MSL and HRV parameters. Results: Severe EDS patients had higher values of standard deviation of all N-N intervals (SDNN), total spectral power (TOT), and low-frequency power (LF) as compared to non-EDS patients, which was indicative of sympathetic stimulation ( P<0.05). Additionally, high-frequency power (HF) was also higher in severe EDS patients, which indicated decreased parasympathetic drive. A significantly positive correlation was found between MSL and the values of SDNN, TOT, LF, and HF in OSA patients. Conclusion: OSA patients with objective EDS have elevated sympathetic drive and decreased parasympathetic drive. A positive correlation was found between this change in neural activity and the shortening of MSL.

[Characteristics of Sleep Electroencephalographic Power in Chronic Insomnia Patients].

OBJECTIVE: To study the sleep electroencephalogram (EEG) power features of patients with chronic insomnia. METHODS: Retrospective analysis was performed with patients who met the ICD-10 diagnostic criteria for chronic insomnia, using polysomnography (PSG) to examine the overnight sleep EEG. The sleep architectures and relative EEG power across five frequency bands during overnight sleep were compared to study the differences between the insomnia and control groups. Furthermore, the correlation between EEG power and various PSG measures was also analyzed. RESULTS: Forty-five subjects were enrolled in the study, including 25 chronic insomniacs (18 females, aged [36.2±10.7] years) and 20 controls (18 females, aged [36.1±7.6] years). Compared to those of the control group, insomnia patients had significantly lower value of delta power ([38.0±6.1] vs. [43.2±5.8], P<0.05) in the NREM1 stage, and increased value of beta power during total NREM, NREM1 and NREM2 (NREM sleep [5.4±2.3] vs. [3.8±1.4], NREM1 [11.3±3.5] vs. [8.7±2.8], and NREM2 [5.7±2.3] vs. [4.4±1.4], all P<0.05). For correlation analyses, in the insomnia group, a significantly positive correlation was found between the delta value during NREM sleep and the duration of NREM3 sleep ( r=0.527). The beta value during NREM sleep was found to be negatively correlated to the duration of NREM3 sleep ( r=－0.767). A positive correlation was found between the beta value during NREM sleep and the duration of NREM1 and NREM2 sleep ( r=0.486 and 0.589, respectively). CONCLUSION: The results suggest that patients with chronic insomnia have decreased low-frequency EEG power, but increased high-frequency EEG power during NREM sleep. The findings indicate that cortex arousal level is elevated in chronic insomniacs during NREM sleep.

[A Review of the Posttraumatic Stress Disorder and Sleep Disturbances].

Post-traumatic stress disorder (PTSD) is characterized by intrusive emotional memory, alertness and avoidance after individuals suffer from one or more traumatic events. With the exception of manifestations, sleep disturbances are also considered to be the core symptoms of PTSD. This article mainly discussed insomnia, nightmares, obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) in patients with PTSD. Existing evidence suggested that insomnia is a predictor of the development of PTSD. Cognitive behavioral therapy for insomnia is an important research direction for treating insomnia in PTSD patients. Nightmares are also the core symptom of PTSD. Prazosin and image rehearsal therapy are effective therapies to treat post-traumatic nightmares. The co-occurrence of obstructive sleep apnea (OSA) is over 40% in patients with PTSD. Preliminary studies have shown that continuous positive airway pressure therapy can improve PTSD symptoms in patients with PTSD comorbid OSA. In the process of diagnosis and treatment of PTSD patients, it is important to firstly evaluate whether PTSD patient comorbid OSA or insomnia, and then clinicians could further develop an appropriate treatment plan for these patients.

Exposure to extinction-associated contextual tone during slow-wave sleep and wakefulness differentially modulates fear expression.

Recent research has used context cues (odor or auditory cues) to target memories during sleep and has demonstrated that they can enhance declarative and procedural memories. However, the effects of external cues re-presented during sleep on emotional memory are still not fully understood. In the present study, we conducted a Pavlovian fear conditioning/extinction paradigm and examined the effects of re-exposure to extinction memory associated contextual tones during slow-wave sleep (SWS) and wakefulness on fear expression. The participants underwent fear conditioning on the first day, during which colored squares served as the conditioned stimulus (CS) and a mild shock served as the unconditioned stimulus (US). The next day, they underwent extinction, during which the CSs were presented without the US but accompanied by a contextual tone (pink noise). Immediately after extinction, the participants were required to take a nap or remain awake and randomly assigned to six groups. Four of the groups were separately exposed to the associated tone (i.e. SWS-Tone group and Wake-Tone group) or an irrelevant tone (control tone, CtrT) (i.e. SWS-CtrT group and Wake-CtrT group), while the other two groups were not (i.e. SWS-No Tone group and Wake-No Tone group). Subsequently, the conditioned responses to the CSs were tested to evaluate the fear expression. All of the participants included in the final analysis showed successful levels of fear conditioning and extinction. During the recall test, the fear responses were significantly higher in the SWS-Tone group than that in the SWS-No Tone group or the SWS-CtrT group, while the Wake-Tone group exhibited more attenuated fear responses than either the Wake-No Tone group or Wake-CtrT group. Otherwise, re-exposure to auditory tones during SWS did not affect sleep profiles. These results suggest that distinct conditions during which re-exposure to an extinction memory associated contextual cue contributes to differential effects on fear expression.

[Occurrence of complex sleep apnea during continuous positive airway pressure therapy].

OBJECTIVE: To explore the occurrence of complex sleep apnea syndrome in patients with obstructive sleep apnea during continuous positive airway pressure titration and evaluate their polysomnographic characteristics. METHODS: A total of 420 patients with obstructive sleep apnea were recruited to undergo an overnight continuous positive airway pressure titration at the Sleep Medicine Center, West China Hospital from January 2010 to December 2012. Their polysomnographic records of respiratory events, oxygen desaturation events and sleep stages were retrospectively reviewed. RESULTS: The incidence of complex sleep apnea syndrome was 7.9% (33/420) and central apnea index (9.0 ± 5.1) /h.No significant differences existed in age, gender, body mass index and titration pressure of continuous positive airway pressure between two groups. Compared with those with non-complex sleep apnea, complex sleep apnea patients had significant increases in apnea/hypopnea index (12.8/h vs 3.6/h, P < 0.05) and oxygen desaturation index (10.3/h vs 3.8/h, P < 0.05) which mainly happened in non-rapid eye movement stage. They also showed decreases in total sleep time ((365 ± 96) vs (402 ± 77) min), rapid eye movement stage (16% ± 8% vs 20% ± 10%) , increases in non-rapid eye movement stage 1 (24% ± 17% vs 15% ± 13%), wakefulness after sleep onset ((108 ± 93) vs (79 ± 61) min) and brief arousal index ((28 ± 15) vs (20 ± 12)/h). And the differences were statistically significant (all P < 0.05). CONCLUSIONS: Complex sleep apnea syndrome is common among Chinese patients with obstructive sleep apnea. Compared with those with non-complex sleep apnea, complex sleep apnea patients have reduced sleep time and worse sleep quality during continuous positive airway pressure therapy.

Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis.

Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.

[Relationship between excessive daytime sleepiness and oxygen saturation in obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate polysomnographic determinants of excessive daytime sleepiness (EDS) and potential relationship in Chinese patients with obstructive sleep apnea-hypopnea syndrome (OSAS). METHODS: A total of 410 patients with obstructive sleep apnea-hypopnea syndrome were analyzed retrospectively who were obtained in Sleep medicine center of West China hospital from January to April in 2010. All of the patients with an apnea-hypopnea index (AHI) greater than 5 h(-1) were evaluated using the Epworth Sleepiness Scale (ESS) and sleep disorders questionnaire. The patients who ESS score was more than 10 were defined as EDS; otherwise, the other was considered to without EDS. RESULTS: A total of 176 patients with EDS (ESS: 15 ± 3) and 234 without EDS (ESS: 6 ± 3) were studied. Patients with EDS were slightly higher BMI (28 ± 4 vs 26 ± 4) and shorter REM sleep latency (99 ± 65 vs 125 ± 81) than patients without EDS. Furthermore, there were significant difference in awake SaO2, AHI, minimum SaO2, oxygen desaturation index and arousal index between EDS group were No-EDS group (P < 0.001). There was a significant difference in waking SaO2 of severe OSAS between both groups. CONCLUSION: Long-term chronic hypoxia already exists in severe OSAS patients with prominent sleepiness. Waking SaO2 may play a role as a predictor in evaluation and diagnosis in patients with OSAS.

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). FINDING: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. INTERPRETATION: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. FUNDING: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels.

Haem is essential for living organisms, functioning as a crucial element in the redox-sensitive reaction centre in haemproteins. During the biogenesis of these proteins, the haem cofactor is typically incorporated enzymatically into the haem pockets of the apo-haemprotein as the functionally indispensable prosthetic group. A class of ion channel, the large-conductance calcium-dependent Slo1 BK channels, possesses a conserved haem-binding sequence motif. Here we present electrophysiological and structural evidence showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain. Both oxidized and reduced haem binds to the hSlo1 channel protein and profoundly inhibits transmembrane K+ currents by decreasing the frequency of channel opening. This direct regulation of the BK channel identifies a previously unknown role of haem as an acute signalling molecule.

Association of Longitudinal Patterns of Habitual Sleep Duration With Risk of Cardiovascular Events and All-Cause Mortality.

Importance: Single self-reported measures of sleep duration are associated with adverse health outcomes; however, long-term patterns of self-reported sleep duration and their association with cardiovascular events (CVEs) and all-cause mortality remain unknown. Objective: To determine whether trajectories of long-term vs single-measure sleep duration are associated with subsequent risk of CVEs and all-cause mortality. Design, Setting, and Participants: The Kailuan study is a prospective, population-based cohort study that began in 2006. The present cohort included 52 599 Chinese adults without atrial fibrillation, myocardial infarction, stroke, or cancer to 2010. Trajectories in sleep duration from January 1, 2006, to December 31, 2010, were identified to investigate the association with risk of CVEs and all-cause mortality from January 1, 2010, to December 31, 2017. Data analysis was conducted from July 1 to October 31, 2019. Exposures: Habitual self-reported nocturnal sleep durations were collected in 2006, 2008, and 2010. Trajectories in sleep duration for 4 years were identified by latent mixture modeling. Main Outcomes and Measures: All-cause mortality and first incident CVEs (atrial fibrillation, myocardial infarction, and stroke) from 2010 to 2017 were confirmed by medical records. Based on the baseline sleep duration and patterns over time, 4 trajectories were categorized (normal stable, normal decreasing, low increasing, and low stable). Results: Of the 52 599 adults included in the study (mean [SD] age at baseline, 52.5 [11.8] years), 40 087 (76.2%) were male and 12 512 (23.8%) were female. Four distinct 4-year sleep duration trajectory patterns were identified: normal stable (range, 7.4 to 7.5 hours [n = 40 262]), normal decreasing (mean decrease from 7.0 to 5.5 hours [n = 8074]), low increasing (mean increase from 4.9 to 6.9 hours [n = 3384]), and low stable (range, 4.2 to 4.9 hours [n = 879]). During a mean (SD) follow-up of 6.7 (1.1) years, 2361 individuals died and 2406 had a CVE. Compared with the normal-stable pattern and adjusting for potential confounders, a low-increasing pattern was associated with increased risk of first CVEs (hazard ratio [HR], 1.22; 95% CI, 1.04-1.43), a normal-decreasing pattern was associated with increased risk of all-cause mortality (HR, 1.34; 95% CI, 1.15-1.57), and the low-stable pattern was associated with the highest risk of CVEs (HR, 1.47; 95% CI, 1.05-2.05) and death (HR, 1.50; 95% CI, 1.07-2.10). Conclusions and Relevance: In this study, sleep duration trajectories with lower or unstable patterns were significantly associated with increased risk of subsequent first CVEs and all-cause mortality. Longitudinal sleep duration patterns may assist in more precise identification of different at-risk groups for possible intervention. People reporting consistently sleeping less than 5 hours per night should be regarded as a population at higher risk for CVE and mortality.

Reactive oxygen species impair Slo1 BK channel function by altering cysteine-mediated calcium sensing.

Vascular dysfunction is a hallmark of many diseases, including coronary heart disease, stroke and diabetes. The underlying mechanisms of these disorders, which are intimately associated with inflammation and oxidative stress caused by excess reactive oxygen species (ROS), have remained elusive. Here we report that ROS are powerful inhibitors of vascular smooth muscle calcium-dependent Slo1 BK or Maxi-K potassium channels, an important physiological determinant of vascular tone. By targeting a cysteine residue near the Ca(2+) bowl of the BK alpha subunit, H(2)O(2) virtually eliminates physiological activation of the channel, with an inhibitory potency comparable to a knockout of the auxiliary subunit BK beta 1. These results reveal a molecular structural basis for the vascular dysfunction involving oxidative stress and provide a solid rationale for a potential use of BK openers in the prevention and treatment of cardiovascular disorders.

Objective sleep duration is associated with cognitive deficits in primary insomnia: BDNF may play a role.

Study Objectives: Objective sleep duration has been linked to insomnia severity. However, cognitive functions of people with insomnia with different sleep durations have been seldom addressed. Brain-derived neurotrophic factor (BDNF) has an important role in cognitive function and has been linked to clinical insomnia recently. The present study aimed to evaluate the comprehensive cognitive functions in people with primary insomnia with different objective sleep durations, and further examine the involvement of peripheral BDNF. Methods: Fifty-seven people with insomnia were subdivided into short sleep duration (SSD, sleep time < 6 hr) group and normal sleep duration (NSD, sleep time ≥ 6 hr) group based on polysomnography data. Twenty-nine healthy controls (HC) were matched on age, gender, and education. Cognitive function was assessed using a comprehensive and sensitive neuropsychological test battery. Both objective and subjective insomnia statuses were estimated. Serum BDNF level was measured using enzyme-linked immune sorbent assay. Results: Compared with HC, the SSD group showed impaired neuropsychological performances in spatial span, brief visuospatial memory test, fluency, managing emotions, and continuous performance tests. In contrast, NSD had bad performance only in brief visuospatial memory test and continuous performance tests, and relatively better than SSD group in the latter test. People with SSD insomnia but not NSD had decreased BDNF levels compared with HC, and neuropsychological performance was positively correlated with BDNF levels only in SSD group. Conclusions: Primary insomnia was associated with impaired neuropsychological performance, and the impairment might be related to decreased objective sleep duration. In addition, decreased peripheral BDNF might mediate the impaired cognitive functions of people with insomnia with SSD.