About one-third of adults have trouble sleeping, ranging from occasional difficulty to chronic insomnia, along with difficulty maintaining sleep. Many studies reported that the long-term use of ...hypnotics can cause brain dysfunction and damage cognition.
The objective of the study is to evaluate whether low, medium, and high doses of orexin dual receptor antagonists (DORA), zopiclone (ZOP), eszopiclone (ESZ), and zolpidem (ZST) can impair cognition.
From the beginning through September 20, 2022, PubMed, Embase, Scopus, the Cochrane Library, and Google Scholar were searched. Randomized controlled trials (RCTs) assessing the therapeutic effects of DORA, eszopiclone, and zopiclone for sleep and cognitive function were included. The primary outcomes were indices related to the cognitive profile, including memory, alertness, execution and control function, and attention and orientation. The secondary outcomes were indices related to sleep and adverse events. The standard mean difference (SMD) was generated for continuous variables. Certain data were captured from figures by GetData 2.26 and analyzed using RStudio 4.2.
Finally, a total of 8,702 subjects were included in 29 studies. Compared with the placebo, the DSST (Digit Symbol Substitution Test) scores of low, medium, and high doses of DORA were SMD = 0.77; 95% CI: 0.33-1.20; SMD = 1.58; 95% CI: 1.11-2.05; and SMD = 0.85; 95% CI: 0.33-1.36, respectively. The DSST scores of zolpidem at low, medium, and high doses were SMD = -0.39; 95% CI: 0.85-0.07; SMD = -0.88, 95% CI: -2.34-0.58; and SMD = -0.12, 95% CI: -0.85-0.60, respectively. Zopiclone's DSST scale score was SMD = -0.18; 95% CI: -0.54-0.18. In addition, the total sleep time (TST) of low, medium, and high doses of DORA was SMD = 0.28, 95% CI: -0.15-0.70; SMD = 1.36, 95% CI: 0.87-1.86; and SMD = 2.59, 95% CI: 1.89-3.30, respectively. The TST of zolpidem with low, medium, and high doses was SMD = 1.01, 95% CI: 0.18-1.83; SMD = 1.94, 95% CI: 0.46-3.43; and SMD = 1.71, 95% CI: 0.86-2.56, respectively. The TST of low, medium, and high doses of eszopiclone was relatively SMD = 2.03, 95% CI: -0.21-4.27; SMD = 2.38, 95% CI: 1.35-3.42; and SMD = 1.71, 95% CI: 0.60-2.82. Zopiclone's TST was SMD = 2.47, 95% CI: 1.36-3.58.
We recommend DORA as the best intervention for insomnia because it is highly effective in inducing and maintaining sleep without impairing cognition. Although zolpidem has a more pronounced effect on maintaining sleep, it is best to reduce its use because of its side effects. Eszopiclone and zopiclone improved sleep quality, but their safety in cognition remains to be verified.
lncRNAs are recently thought to play a significant role in cellular homeostasis during pathological process of diseases by competing inhibiting miRNA function. The aim of present study was to assess ...the function of long non-coding RNA (lncRNA) MEG3 and its functional interaction with microRNA-181b in cerebral ischemic infarct of mice and hypoxia-induced neurons apoptosis.
To address this question, we performed the experiments with in vivo middle cerebral artery occlusion (MCAO) mice model and in vitro oxygen-glucose deprivation (OGD)-cultured neuronal HT22 cell line. Relative expression of MEG3, miR-181b, and 12/15-LOX (lipoxygenase) mRNA was determined using quantitative RT-PCR. Western blot was used to evaluate 12/15-LOX protein expression. TUNEL assay was performed to assess cell apoptosis.
In both MCAO mice and OGD-cultured HT22 cell, ischemia, or hypoxia treatment results in a time-dependent increase in MEG3 and 12/15-LOX expression and decrease in miR-181b expression. Knockdown of MEG3 contributes to attenuation of hypoxia-induced apoptosis of HT22 cell. Also, expression level of MEG3 negatively correlated with miR-181b expression and positively correlated with 12/15-LOX expression. In contrary to MEG3, miR-181b overexpression attenuated hypoxia-induced HT22 cell apoptosis, as well as suppressed hypoxia-induced increase in 12/15-LOX expression. By luciferase reporter assay, we concluded that miR-181b directly binds to 12/15-LOX 3'-UTR, thereby negatively regulates 12/15-LOX expression.
Our data suggested that long non-coding RNA MEG3 functions as a competing endogenous RNA for miR-181b to regulate 12/15-LOX expression in middle cerebral artery occlusion-induced ischemic infarct of brain nerve cells.
Objectives
Narcolepsy patients were observed improvements in their academic performance during the COVID-19 home quarantine. Therefore, we aim to investigate the influence of sleep behavioral changes ...on school/work performance in narcolepsy patients during the home quarantine.
Methods
Patients admitted to Shandong Provincial Qianfoshan Hospital from Jan 1, 2017 to Jan 1, 2021 who were diagnosed with narcolepsy were studied by online questionnaires in two different periods (during and 1 year after the COVID-19 home quarantine), including five aspects: (1) changes in school/work performance (percentile ranking in class/Sheehan Disability Scale 1, SDS1); (2) daytime functions; (3) clinical symptoms; (4) psychological moods; (5) medication situations.
Results
A total of 46 narcolepsy patients 34 (73.9%) narcolepsy type 1, 12 (26.1%) narcolepsy type 2 with average age of 20.76 ± 8.99 years and an equal number of age and gender matched control subjects were enrolled. During the COVID-19 home quarantine, the narcolepsy patients were found that they altered sleep patterns, including later get up time (
P
< 0.001), longer total sleep time (TST,
P
= 0.001), better sleep quality (PSQI,
P
= 0.001), and lower anxiety level (
P
= 0.005). Their school/work performance improved parallelly with better percentile ranking (
P
= 0.001) and lower SDS1 scores (
P
= 0.002). The results of multiple linear stepwise regression analysis showed a linear regression relationship between TST efficient (95%) −7.356 (−13.570 to 1.143), SDS1 score efficient (95%) 6.580 (2.346–10.815),
P
= 0.004 and the percentile ranking after adjusting for potential effects. Both the improvements of sleep behavior and school/work performance disappeared after the end of COVID-19 home quarantine. No similar fluctuation was found in the control group.
Discussion
Changes in sleep pattern during the COVID-19 home quarantine, such as longer sleep time and later wake-up time, can reduce the degree of daytime sleepiness and increase the degree of daytime wakefulness of narcolepsy patients, which can alleviate the impact of the disease on school/work performance.
Insomnia is a common disease, and the application of various types of sleeping pills for cognitive impairment is controversial, especially as different doses can lead to different effects. Therefore, ...it is necessary to evaluate the cognitive impairment caused by different sleeping pills to provide a theoretical basis for guiding clinicians in the selection of medication regimens.
To evaluate whether various different doses (low, medium and high) of anti-insomnia drugs, such as the dual-orexin receptor antagonist (DORA), zopiclone, eszopiclone and zolpidem, induce cognitive impairment.
The PubMed, Embase, Scopus, Cochrane Library, and Google Scholar databases were searched from inception to September 20th, 2022 for keywords in randomized controlled trials (RCTs) to evaluate the therapeutic effects of DORA, eszopiclone, zopiclone and zolpidem on sleep and cognitive function. The primary outcomes were indicators related to cognitive characteristics, including scores on the Digit Symbol Substitution Test (DSST) and daytime alertness. The secondary outcomes were the indicators associated with sleep and adverse events. Continuous variables were expressed as the standard mean difference (SMD). Data were obtained through GetData 2.26 and analyzed by Stata v.15.0.
A total of 8702 subjects were included in 29 studies. Eszopiclone
significantly increased the daytime alertness score (SMD = 3.00, 95 % CI: 1.86 to 4.13) compared with the placebo, and eszopiclone
significantly increased the daytime alertness score (SMD = 4.21, 95 % CI: 1.65 to 6.77; SMD = 3.95, 95 % CI: 1.38 to 6.51; SMD = 3.26, 95 % CI: 0.38 to 6.15; and SMD = 3.23, 95 % CI: 0.34 to 6.11) compared with zolpidem
, zolpidem
, DORA
, and eszopiclone
, respectively. Compared with the placebo, zopiclone, zolpidem
, and eszopiclone
, DORA significantly increased the TST (SMD = 2.39, 95 % CI: 1.11 to 3.67; SMD = 6.00, 95 % CI: 2.73 to 9.27; SMD = 1.89, 95 % CI: 0.90 to 2.88; and SMD = 1.70, 95 % CI: 0.42 to 2.99, respectively).
We recommend DORA as the best intervention for insomnia because it was highly effective in inducing and maintaining sleep without impairing cognition. Although zolpidem had a more pronounced effect on sleep maintenance, this drug is better for short-term use. Eszopiclone and zopiclone improved sleep, but their cognitive effects have yet to be verified.
With the transformation of the trend of vehicle electrification, the overall noise level in the vehicle is gradually reduced. The problem of low-frequency noise in the vehicle, which was previously ...ignored, is becoming more and more prominent. To solve the vehicle low-frequency noise problem, a combination of real-vehicle tests and simulation analysis is carried out. During the test, the driver and passengers feel that there is a relatively obvious low-frequency roar noise in the car, which results from the structural radiation noise of the trunk door vibration. Therefore, to solve this problem, we design an acoustic metamaterial with lightweight and miniaturized features based on the local resonance principle of phononic crystals. Firstly, the selection of the resonant unit configuration and the design of the band gap are implemented. Then, the layout planning of the whole vehicle, the layout of the resonance unit and the design of the base frame are implemented. The actual vehicle test results show that: after attaching the designed acoustic metamaterial, the low-frequency noise sound pressure levels in the front and rear of the vehicle were reduced by 2.0 dB (A) and 2.3 dB (A), respectively, meanwhile, the interior noise sound quality was improved. The sound pressure level at the driver's right ear in the car has an abnormal peak of around 35Hz. In addition, the driver and passengers feel that there is a relatively obvious low-frequency roar noise in the car, and through low-pass filtering of the collected signals, it is confirmed that the peak frequency is the main cause of the low-frequency roar in the car. The low-frequency steady-state noise of the car is generally considered to be the low-frequency vibration of the body panel and the radiation occurs. Through the finite element simulation analysis (Grid Participation Analysis) of the abnormal peak frequency, the results show that the low-frequency roar is caused by the low-frequency vibration of the tailgate sheet metal, and the problem peak frequency is not coupled with the acoustic cavity mode. Facing the problem of the low-frequency roar radiated into the car by the vibration of the tailgate sheet metal parts, based on the local resonance band gap theory, we developed a design to suppress the 35 Hz vibration of the tailgate sheet metal parts and meet the characteristics of lightweight and miniaturization. By attaching the acoustic metamaterial to the tailgate and performing CAE simulation of the whole vehicle, it is determined that the structure can indeed reduce the 35 Hz noise in the car and the peak value of the tailgate sheet metal vibration.
Early neurological deterioration (END) sometimes occurs in patients with penetrating artery territory infarction (PATI) and leads to poor prognosis. In this study, we analyzed clinical and ...neuroimaging characteristics of PATI, and focused on the infarct patterns on diffusion-weighted imaging (DWI). We tried to investigate whether the "island sign" pattern is associated with END.
We enrolled consecutive patients admitted with acute PATI within 48 h after onset from May 2020 to July 2022. They were divided into with and without the "island sign" pattern on DWI. According to infarct location, all the patients were classified into two groups: the territories of the lenticulostriate arteries (LSA) and paramedian pontine arteries (PPA). The patients in each group were further divided into two groups according to whether they developed END or not. Through analyzing the clinical and neuroimaging characteristics of the patients, we tried to identify the factors that might associated with the "island sign" pattern and the potential predictors of END within the LSA and PPA groups.
Out of the 113 patients enrolled in this study, END was found in 17 patients (27.9%) in the LSA group and 20 patients (38.5%) in the PPA group. The "island sign" was found in 26 (23%) patients. In the multivariate analysis, the independent predictors of END in the LSA group were the "island sign" (OR 4.88 95% CI 1.03-23.2 P = 0.045) and high initial National Institute of Health Stroke Scale (NIHSS) (OR 1.79 95% CI 1.08-2.98 P = 0.024) and in the PPA group was the presence of lesions extending to the ventral pontine surface (OR 7.53 95% CI 1.75-32.37 P = 0.007).
The predictive factors for END were different in the LSA and PPA groups. The "island sign" was particularly associated with END in the LSA group.
At present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human ...leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB1*0602/DQA1*0102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB1*0602/DQA1*0102 and clinical manifestations in Chinese patients with narcolepsy.
Narcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5.
A total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was *0602 (89.7%), and the most common genotype at this locus was *0602*0301 (19.2%), followed by *0602*0602 (17.9%). The most common phenotype of the HLA-DQA1 locus is *0102 (92.6%), and the most common genotype of this locus is *0102*0102 (27.8%), followed by *0102*0505 (14.8%). There were significant differences (
< 0.05) between HLA-DQB1*0602-positive and HLA-DQB1*0602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA1*0102-positive and HLA-DQA1*0102-negative patients showed significant differences (
< 0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB1*0602/DQA1*0102 homozygous and heterozygous patients
< 0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters.
Different genotypes of HLA-DQA1*0102/DQB1*0602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness.
Abstract
Background
Primary familial brain calcification (PFBC) is a rare inherited neurological disorder characterized by bilateral basal ganglia calcification with a series of motor and nonmotor ...symptoms. Mutations in the
SLC20A2
gene, encoding the PiT2 protein, are the major cause of the disease. Here, we report a Chinese PFBC family carrying a
SLC20A2
gene mutation, and the proband presented with purely acute psychiatric symptoms, which has been rarely reported in this disease.
Case presentation
A 38-year-old woman was hospitalized due to disorganized speech; disordered thought contents; disorganized behaviour; emotional instability and lability; and grandiose words, actions and facial expressions. Brain computerized tomography (CT) revealed calcification in the basal ganglia; cerebellar dentate nuclei; and subcortical, periventricular, and deep white matter regions in she and her family members. Through mutation analysis, a heterozygous truncating mutation, c.1723G > T, p.(Glu575*), was identified in the
SLC20A2
gene in this family. Thus, this patient was diagnosed with genetically confirmed PFBC, and she responded well to a low dose of antipsychotic drugs. The penetrance of the disease in this family was only 33%, which was significantly lower than that in most families carrying
SLC20A2
gene mutations.
Conclusions
Patients with
SLC20A2-
related PFBC might present with psychiatric symptoms alone, and the penetrance of the disease may be quite low, which adds to the clinical heterogeneity of the disease.
Background:
Behcet's disease (BD) is multi-systemic vasculitis, which generally is repeated oral and genital ulcerations as well as ocular and skin lesions. Today, the pathogenesis of BD remains ...mostly unknown. It is also suggested that the disease is probably related to autoinflammatory and autoimmune disorders, and innate immunity damages were perceived as key in its pathologic process. Only 5% of BD patients have neurological involvement, and it usually occurs in 4–6 years after the initial symptoms. Early onset of neurological impairment makes it difficult to diagnose and treat definitely.
Case Presentation:
A 38-year-old man was admitted to our hospital with numbness and weakness of the left extremities. Diffusion magnetic resonance imaging (MRI) revealed focal infarction in the posterior limb of the internal capsule. Skin pathology suggested small vessel vasculitis, and high-resolution MRI revealed intracranial arteritis. The patient had a negative skin pathery test and then developed a scar at the venous puncture site at the early stage of disease. Laboratory examination showed that interleukin 8 (IL-8) increased. The patient was treated with an immunosuppressive agent including mycophenolate mofetil, hydroxychloroquine, and colchicine. All symptoms were alleviated after half a year's treatment. There was neither stroke nor recurrence of oral ulcer thereafter.
Conclusion:
This case demonstrates that neurological involvement might be an early symptom of BD. IL-8 could act as a novel target for the treatment of BD theoretically and probably play a key role in disease recovery.
As a medium for developing brain-computer interface systems, EEG signals are complex and difficult to identify due to their complexity, weakness, and differences between subjects. At present, most of ...the current research on sleep EEG signals are single-channel and dual-channel, ignoring the research on the relationship between different brain regions. Brain functional connectivity is considered to be closely related to brain activity and can be used to study the interaction relationship between brain areas.
Phase-locked value (PLV) is used to construct a functional connection network. The connection network is used to analyze the connection mechanism and brain interaction in different sleep stages. Firstly, the entire EEG signal is divided into multiple sub-periods. Secondly, Phase-locked value is used for feature extraction on the sub-periods. Thirdly, the PLV of multiple sub-periods is used for feature fusion. Fourthly, the classification performance optimization strategy is used to discuss the impact of different frequency bands on sleep stage classification performance and to find the optimal frequency band. Finally, the brain function network is constructed by using the average value of the fusion features to analyze the interaction of brain regions in different frequency bands during sleep stages.
The experimental results have shown that when the number of sub-periods is 30, the α (8-13 Hz) frequency band has the best classification effect, The classification result after 10-fold cross-validation reaches 92.59%.
The proposed algorithm has good sleep staging performance, which can effectively promote the development and application of an EEG sleep staging system.
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