Pseudo[n]-pillar[5]arenes: Synthesis, Structures, and Host-Guest Binding Properties.

[1n]Paracyclophane has been known for nearly 40 years, but its derivatives and properties are understudied in comparison to those of other macrocyclic compounds. By the modification of pillar[5]arene, we successfully obtained five electron-rich pentagonal macrocycles (pseudo[n]-pillar[5]arenes, n = 1-4) with the decrease of substituted phenylenes one after another, achieving the partial derivatization of [15]paracyclophane skeleton at its phenylene sites. Pseudo[n]-pillar[5]arenes (P[n]P[5]s) served as a kind of macrocyclic host to form complexes with various guests, such as dinitriles, dihaloalkanes, and imidazolium salt, in a 1:1 host-guest stoichiometric ratio. The binding constants with the guest gradually reduce along the decrease of substituted phenylene segments from host P[1]P[5] to P[4]P[5]. It is worthy to note that P[n]P[5]s can adjust their conformations to the "pillar-like" shape effectively when binding with succinonitrile in the solid state.

Relationship between sarcopenia and sleep status in female patients with mild to moderate Alzheimer's disease.

BACKGROUND: Sleep disorders and sarcopenia could contribute to the development of Alzheimer's disease (AD), which are risk factors that rapidly deteriorate cognitive functions. However, few studies have evaluated the relationship between sarcopenia and sleep disorders in female AD patients, who have a higher prevalence than male patients. This study aimed to investigate the relationship between sarcopenia and sleep status in female patients with mild to moderate AD. METHODS: This cross-sectional study recruited 112 female outpatients aged between 60 and 85 years. Demographic characteristics, appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were assessed. Sarcopenia was diagnosed according to criteria of the Asian Working Group for Sarcopenia. Pittsburgh Sleep Quality Index (PSQI) assessed sleep variables. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessed cognitive function. Binary logistic regression models explored the relationship between sleep variables and cognitive function and sarcopenia, adjusting for potential cofounders. RESULTS: The outpatients were divided into 36 AD patients with sarcopenia (ADSa) and 76 AD patients without sarcopenia (ADNSa), with a prevalence of 32.1%. ADSa had lower ASMI, weaker grip strength, slower gait speed, a higher incidence of poor sleep quality and poorer cognitive function. Multivariate binary logistic regression analysis showed that high total scores of PSQI (odds ratio (OR) = 1.13), poor sleep quality (OR = 2.73), poor subjective sleep quality (OR = 1.83), low MMSE (OR = 0.77) and MoCA (OR = 0.76) scores were associated with high odds of sarcopenia. Compared to sleep time ≤ 15 min, >60 min (OR = 5.01) were associated with sarcopenia. Sleep duration <6 h (OR = 3.99), 8-9 h (OR = 4.48) and ≥9 h (OR = 6.33) were associated with sarcopenia compared to 7-8 h. CONCLUSIONS: More sleep symptoms and cognitive impairment exist in female patients with sarcopenia. The higher total scores of PSQI, poorer subjective sleep quality, longer sleep latency, excessive and insufficient sleep duration and poorer cognitive function are associated with higher odds of sarcopenia in female patients with mild to moderate AD.

Restless legs syndrome and perceived olfactory and taste dysfunction: A community-based study.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) has been suggested as a prodromal symptom of Parkinson disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction. METHODS: We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or the Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history. RESULTS: RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio = 5.92, 95% confidence interval = 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio = 5.55, 95% confidence interval = 2.37-13.0) or when excluding participants with major chronic diseases. CONCLUSIONS: RLS was associated with increased odds of perceived olfactory and taste dysfunction.

Bilateral facial colliculus syndrome caused by pontine tegmentum infarction: a case report.

BACKGROUND: Bilateral facial colliculus syndrome is a rare clinical presentation in patient with pontine infarction. We herein described a case of bilateral facial paralysis and complete horizontal gaze palsy possibly caused by paradoxical embolization from patent foramen ovale related stroke. CASE PRESENTATION: A 55-year-old male presented with sudden onset of complete peripheral facial palsy and horizontal gaze palsy after Valsava maneuver. MRI revealed symmetric involvement of bilateral pontine tegmentum in accordance with the location of facial colliculus. CSF analysis and follow-up MRI showed no evidence of central demyelinating disease. Subsequent echocardiography revealed patent foramen ovale and closure surgery was performed. CONCLUSIONS: Facial colliculus syndrome with symmetric dorsal pontine tegmentum involvement may a rare manifestation in posterior circulation stroke.

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson's disease.

BACKGROUND: The clinical characteristics of Parkinson's disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression. OBJECTIVE: To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO). METHODS: Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality. RESULTS: Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep. CONCLUSION: More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.

Effect of sidedness on survival among patients with early-stage colon cancer: a SEER-based propensity score matching analysis.

BACKGROUND: Most previous studies compared survival between left-sided and right-sided colon cancer without adjustment for clinicopathological parameters. We investigated the effect of sidedness on survival among patients with early-stage colon cancer, using a propensity score matching method. METHODS: The 18 registry custom data within the SEER database were used to identify patients who were diagnosed with colon cancer between 2010 and 2014. A propensity score matching analysis was performed using the nearest neighbor method. Survival was estimated using the Kaplan-Meier method. A Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: In the unmatched cohort, 25,094 (35.72%) patients were diagnosed with left-sided colon cancer and 45,156 (64.28%) with right-sided colon cancer. After propensity score matching, each cohort included 5118 patients, and the clinicopathological characteristics were well balanced. In the unmatched cohort, left-sided colon cancer had superior all-cause (χ2=315, P<0.01) and cancer-specific (χ2=43, P<0.01) survival than right-sided tumors. However, in the matched cohort, no difference was observed for all-cause (χ2=0.7, P=0.4) and cancer-specific (χ2=0, P=0.96) survival between left and right colon cancer. The Cox model did not indicate sidedness as a prognostic factor. In the subgroup analysis, stage II right-sided colon cancer had a better survival outcome, while stage III left-sided tumors had a better survival outcome. CONCLUSIONS: After adjusting for clinicopathological characteristics in this study, sidedness showed no impact on survival in early-stage colon cancer. However, sidedness was associated with prognostic differences in stages II and III early-stage colon cancer.

Synthesis of i-Corona[6]arenes for Selective Anion Binding: Interdependent and Synergistic Anion-π and Hydrogen-Bond Interactions.

i-Corona[3]arene[3]tetrazines were synthesized from the nucleophilic aromatic substitution reaction of resorcinol and its derivatives with 3,6-dichlorotetrazine in a one-pot fashion under mild conditions. All of the resulting macrocycles adopted 1,3,5-alternate conformation irrespective of the nature of the substituents on both upper- and lower-rims. i-Corona[3]arene[3]tetrazine was found to self-regulate its macrocyclic conformation and cavity to recognize anions with binding constants spanning from 26 M-1 to 2.2×103  M-1 depending on the structure of the anions. The selective binding resulted from a significant interdependent and synergistic effect between multiple tetrazine π/anion and Caryl -H/anion hydrogen bond interactions. Taking advantage of synergistic effect revealed, a cyanobenzene-embedded i-corona[3]arene[3]tetrazine was designedly synthesized and highly selective and very strong affinity toward nitrate with a binding constant of 2.2×105  M-1 was achieved.

Modular Strategy for Constructing para-Cage[n]arenes, meta-Cage[n]arenes, and meta-Bimacrocyclic-Arenes.

Here, we present a versatile modular strategy for crafting novel covalent organic cages (para-cage[n]arenes and meta-cage[n]arenes, n = 3,4) and bimacrocycles (meta-bimacrocyclic-arenes) with stable backbones and modifiable rims. These structures can be synthesized from commercially available aromatic multialdehydes in a three-step process: quantitative bromination, Suzuki-Miyaura reaction (yielding over 60%), and a rapid one-pot Friedel-Crafts reaction with paraformaldehyde. Notably, the cage[n]arenes exhibit a well-defined prismatic shape, and the bimacrocyclic-arenes display both dimeric and monomeric configurations.

Objective sleep enhancement in Parkinson's disease: A sham-controlled trial of low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex.

INTRODUCTION: Parkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients. METHODS: In this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS. RESULTS: The rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5-2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes. CONCLUSION: Low-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.

Higher cortical excitability to negative emotions involved in musculoskeletal pain in Parkinson's disease.

OBJECTIVE: Changes in brain structure and neurotransmitter systems are involved in pain in Parkinson's disease (PD), and emotional factors are closely related to pain. Our study applied electroencephalography (EEG) to investigate the role of emotion in PD patients with chronic musculoskeletal pain. METHODS: Forty-two PD patients with chronic musculoskeletal pain and 38 without were enrolled. EEG data were recorded under resting conditions, and while viewing pictures with neutral, positive, and negative content. We compared spectrum power, functional connectivity, and late positive potential (LPP), an event-related potential (ERP), between the groups. RESULTS: PD patients with pain tended to have higher scores for the Hamilton Rating Scale for Depression (HRSD). In the resting EEG, mean ß-band amplitude was significantly higher in patients with pain than in those without. Logistic regression analysis showed that higher HRSD scores and higher mean ß-band amplitude were associated with pain. ERP analysis revealed that the amplitudes of LPP difference waves (the absolute difference between positive and negative condition LPP and neutral condition LPP) at the central-parietal region were significantly reduced in patients with pain (P = 0.029). Spearman correlation analysis showed that the amplitudes of late (700-1000 ms) negative versus neutral condition LPP difference waves were negatively correlated with pain intensity, assessed by visual analogue scale, (r = -0.393, P = 0.010) and HRSD scores (r = -0.366, P = 0.017). CONCLUSION: Dopaminergic and non-dopaminergic systems may be involved in musculoskeletal pain in PD by increasing ß-band activity and weakening the connection of the θ-band at the central-parietal region. PD patients with musculoskeletal pain have higher cortical excitability to negative emotions. The changes in pain-related EEG may be used as electrophysiological markers and therapeutic targets in PD patients with chronic pain.

Association Between Sleep Characteristics and Likelihood of Prodromal Parkinson's Disease: A Cross-Sectional Analysis in the HABIT Study.

Background: Sleep is critical in health problems including Parkinson's disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD. Methods: At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension. Results: Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (ß = 0.02, 95% CI: 0.01-0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02-1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01-0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04-1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD. Conclusion: Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.

Lack variation of low slow-wave activity over time in the frontal region in NREM sleep may be associated with dyskinesia in Parkinson's disease.

OBJECTIVE: Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. METHODS: We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. RESULTS: Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. CONCLUSION: PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.

Macrocycles and Acyclic Cucurbit[n]urils as Pseudo[2]catenane Partners for Long-Acting Neuromuscular Blocks and Rapid Reversal In Vivo.

Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit[n]urils (ACBs) can form such partners by functioning as long-acting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with Ka values of over 109 M-1. In vivo experiments with rats reveal that, at the dose of 2- and 3-fold ED90, one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.

Structure-Activity Relationship Studies Leading to the Discovery of Highly Water-Soluble and Biocompatible Acyclic Cucurbit[n]uril FY-3451 as a Universal Antagonist That Rapidly Reverses Neuromuscular Blocking Agents In Vivo.

The development of a reversal agent that can rapidly reverse clinically used nondepolarizing neuromuscular blocking agents (NMBAs) has long been a challenge. Here, we report the synthesis of a series of highly water-soluble acyclic cucurbit[n]urils (acCBs). Systematic structure-activity relationship studies reveal that introducing two propylidene units on the peripheral benzene rings not only remarkably improves the activity of the corresponding derivative acCB6 (FY 3451) in reversing the neuromuscular block of rocuronium, cisatracurium, vecuronium, and pancuronium, the four clinically used NMBAs, through stable inclusion, but also allows for high water-solubility as well as a maximum tolerated dose (2000 mg/kg on rats). In vivo experiments with rats show that, at the identical dose of 25 mg/kg, for rocuronium, vecuronium, and pancuronium, acCB6 can achieve a recovery time shorter than that of sugammadex for rocuronium and, at the dose of 100 mg/kg, realize comparably rapid reversal for cisatracurium.

miR-29 mediates TGFß1-induced extracellular matrix synthesis through activation of PI3K-AKT pathway in human lung fibroblasts.

TGFß1 is very important in the synthesis and degradation of extracellular matrix, and also in the mediation of human lung fibroblasts proliferation, and miR-29 plays an important role in this process. To explore the interactions of miR-29 family members and TGFß1, the effects of transforming growth factor TGFß1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFß1 were examined in human lung fibroblasts. Treatment of the human embryonic lung fibroblast cell line IMR90 with TGFß1 caused a decrease in expression of miR-29a/b/c by real-time PCR analysis. TGFß1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFß1-induced phenotype changes in IMR90 cells. Western blot analyses showed that TGFß1 treatment unchanged total protein expression levels of PI3K or AKT, but the expression levels of p-PI3K, p-AKT, and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked phosphorylation of PI3K or AKT and decreased expression of COL1A1 after TGFß1 treatment. The results indicate that TGFß1 beta uses the PI3k-Akt pathway in these embryonic fibroblasts and miR29 blocks this activation pathway. It indicates a novel biological function of the PI3K-Akt pathway in IMR90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human lung fibroblasts.

Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China.

BACKGROUND: Studies suggest seasonal fluctuations of symptoms in Parkinson's disease (PD) patients in Western countries. However, the association between seasonal change and variation in nonmotor symptoms (NMS) in Chinese PD patients is unclear. Here, we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China. METHODS: We studied 1005 PD patients between April 2008 and October 2020. Patients were classified into four seasons according to the 24 Chinese solar terms, based on assessment date. We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity. RESULTS: Among the 1005 patients studied, the mean age was 64.2 ±â€Š9.7 years and 569 (56.6%) of them were men. Relative to the summer group, patients assessed during winter had higher Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction (SCOPA-AUT) scores ( P  = 0.045). The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer ( P  = 0.009). Among patients who completed polysomnography during the same period ( n  = 135), compared with summer follow-ups, we observed a higher percentage of NREMS1 in winter and spring follow-ups ( P  = 0.042, P  = 0.011), a higher NREMS1 time in spring follow-ups ( P  = 0.0024), a lower NREMS2 time in winter follow-ups ( P  = 0.007), and a higher percentage of phasic rapid eye movement (REM)-sleep without atonia in autumn and winter follow-ups ( P  = 0.026 and P  = 0.020, respectively). In a subset of patients with PD and REM sleep behavior disorder (RBD; n  = 182), those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1 (dream-related sub-score) than those visited during summer ( P  = 0.034, P  = 0.020). We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis. CONCLUSIONS: PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter, and less sleep disturbance than those in spring and winter, suggesting that seasonal change and NMS fluctuation are related, especially in patients with early stage PD.

Circadian disruption and sleep disorders in neurodegeneration.

Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.

Prospective study of sleep duration, snoring and risk of heart failure.

OBJECTIVE: To investigate whether nighttime sleep duration and snoring status were associated with incident heart failure (HF). METHODS: A prospective study was conducted based on Kailuan cohort including 93 613 adults free of pre-existing cardiovascular diseases. Sleep duration and snoring status were assessed by self-reported questionnaire. Incident HF cases were ascertained by medical records. Cox proportional hazards model was applied to calculate the HR and 95% CI of risk of developing HF. Mediation analysis was used to understand whether hypertension and diabetes mediated the association between sleep duration, snoring and HF. Data analysis was performed from 1 June 2021 to 1 June 2022. RESULTS: During a median follow-up of 8.8 years, we documented 1343 incident HF cases. Relative to sleep duration of 7.0-7.9 hour/night, short sleep duration was associated with higher risk of developing HF: adjusted HR was 1.24 (95% CI 1.01 to 1.55) for <6 hours/night and 1.29 (95% CI 1.06 to 1.57) for 6.0-6.9 hours/night, after adjustment for potential confounders such as age, sex, smoking, hypertension and diabetes. A similar 20%-30% higher risk of incident HF was found in individuals reporting occasional or frequent snoring relative to never/rare snorers: adjusted HR was 1.32 for occasional snoring (95% CI 1.14 to 1.52) and 1.24 (95% CI 1.06 to 1.46) for frequent snoring. Presence of diabetes significantly mediated the association between both short sleep duration and snoring and HF risk and hypertension significantly mediated the snoring-HF relationship. CONCLUSION: Short sleep duration and snoring were associated with high risk of HF.

Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy.

We describe three cases of overlapping Epstein-Barr virus (EBV) Encephalitis and Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A). The three cases all presented with initial symptoms of fever, headache, coma, and posture tremor of the upper limbs, then followed by limb weakness and dysuria. All of the three cases were on ventilators. Case 1 and 2 improved dramatically after intravenous methylprednisoloneand immunoglobulin treatment. However, case 3 presented dyspneic, and died from gastrointestinal hemorrhage. The GFAP-A triggered by EBV intracranial infection could initially masquerade as EBV encephalitis only, and the detection of GFAP antibody is essential for differentiation.