Alterations of Audiovisual Integration in Alzheimer's Disease.

Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer's disease (AD). In this review, we evaluated the altered audiovisual integrative behavioral symptoms in AD. We further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD, including the imbalance between energy demand and supply, activity-dependent degeneration, disrupted brain networks, and cognitive resource overloading. Then, based on the clinical characteristics including electrophysiological and imaging data related to audiovisual integration, we emphasized the value of audiovisual integration alterations as potential biomarkers for the early diagnosis and progression of AD. We also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD patients. Moreover, investigation into audiovisual integration alterations in AD also provided new insights and comprehension about sensory information processes.

Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study.

Background: Neurological disorders, such as Alzheimer's disease (AD), comprise a major cause of health-related disabilities in human. However, biomarkers towards pathogenesis or novel targets are still limited. Objective: To identify the causality between plasma proteins and the risk of AD and other eight common neurological diseases using a Mendelian randomization (MR) study. Methods: Exposure data were obtained from a genome-wide association study (GWAS) of 2,994 plasma proteins in 3,301 healthy adults, and outcome datasets included GWAS summary statistics of nine neurological disorders. Inverse variance-weighted MR method as the primary analysis was used to estimate causal effects. Results: Higher genetically proxied plasma myeloid cell surface antigen CD33 level was found to be associated with increased risk of AD (odds ratio [OR] 1.079, 95% confidence interval [CI] 1.047-1.112, p = 8.39×10-7). We also discovered the causality between genetically proxied elevated prolactin and higher risk of epilepsy (OR = 1.068, 95% CI = 1.034-1.102; p = 5.46×10-5). Negative associations were identified between cyclin-dependent kinase 8 and ischemic stroke (OR = 0.927, 95% CI = 0.896-0.959, p = 9.32×10-6), between neuralized E3 ubiquitin-protein ligase 1 and migraine (OR = 0.914, 95% CI = 0.878-0.952, p = 1.48×10-5), and between Fc receptor-like protein 4 and multiple sclerosis (MS) (OR = 0.929, 95% CI = 0.897-0.963, p = 4.27×10-5). Conclusion: The findings identified MR-level protein-disease associations for AD, epilepsy, ischemic stroke, migraine, and MS.

Causal effects of COVID-19 on structural changes in specific brain regions: a Mendelian randomization study.

BACKGROUND: Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure and cognitive function, but it remains unclear whether COVID-19 causes brain structural changes and which specific brain regions are affected. Herein, we conducted a Mendelian randomization (MR) study to investigate this causal relationship and to identify specific brain regions vulnerable to COVID-19. METHODS: Genome-wide association study (GWAS) data for COVID-19 phenotypes (28,900 COVID-19 cases and 3,251,161 controls) were selected as exposures, and GWAS data for brain structural traits (cortical thickness and surface area from 51,665 participants and volume of subcortical structures from 30,717 participants) were selected as outcomes. Inverse-variance weighted method was used as the main estimate method. The weighted median, MR-Egger, MR-PRESSO global test, and Cochran's Q statistic were used to detect heterogeneity and pleiotropy. RESULTS: The genetically predicted COVID-19 infection phenotype was nominally associated with reduced cortical thickness in the caudal middle frontal gyrus (ß = - 0.0044, p = 0.0412). The hospitalized COVID-19 phenotype was nominally associated with reduced cortical thickness in the lateral orbitofrontal gyrus (ß = - 0.0049, p = 0.0328) and rostral middle frontal gyrus (ß = - 0.0022, p = 0.0032) as well as with reduced cortical surface area of the middle temporal gyrus (ß = - 10.8855, p = 0.0266). These causal relationships were also identified in the severe COVID-19 phenotype. Additionally, the severe COVID-19 phenotype was nominally associated with reduced cortical thickness in the cuneus (ß = - 0.0024, p = 0.0168); reduced cortical surface area of the pericalcarine (ß = - 2.6628, p = 0.0492), superior parietal gyrus (ß = - 5.6310, p = 0.0408), and parahippocampal gyrus (ß = - 0.1473, p = 0.0297); and reduced volume in the hippocampus (ß = - 15.9130, p = 0.0024). CONCLUSIONS: Our study indicates a suggestively significant association between genetic predisposition to COVID-19 and atrophy in specific functional regions of the human brain. Patients with COVID-19 and cognitive impairment should be actively managed to alleviate neurocognitive symptoms and minimize long-term effects.

Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: The incidence of gastroesophageal reflux disease (GERD) has been shown to be elevated in individuals with epilepsy. Traditional observational studies have led to a limited understanding of the effects of GERD and BE on epilepsy due to the interference of reverse causation and potential confounders. METHODS: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to determine whether GERD and BE can increase the risk of epilepsy. Genome-wide association study data on epilepsy and its subgroups were obtained from the International League Against Epilepsy consortium for primary analysis using three MR approaches and the FinnGen consortium for replication and meta-analysis. We calculated causal estimates between the two esophageal diseases and epilepsy using the inverse-variance weighted method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. RESULTS: We found a potential effect of genetically predicted GERD on the risk of epilepsy (odds ratio [OR] = 1.078; 95% confidence interval [CI], 1.014-1.146, p = .016). Specifically, GERD showed an effect on the risk of generalized epilepsy (OR = 1.163; 95% CI, 1.048-1.290, p = .004) but not focal epilepsy (OR = 1.059, 95% CI, 0.992-1.131, p = .084). Notably, BE did not show a significant causal relationship with the risks of generalized and focal epilepsy. CONCLUSIONS: Under MR assumptions, our findings suggest a potential risk-increasing effect of GERD on epilepsy, especially generalized epilepsy. Considering the exploratory nature of our study, the association between GERD and epilepsy needs to be confirmed by future prospective studies.

A pyroptosis-related signature predicts prognosis and indicates immune microenvironment infiltration in glioma.

BACKGROUND: Glioma, the most common malignant brain tumor, leads to high recurrence rates and disabilities in patients. Pyroptosis is an inflammasomes-induced programmed cell death in response to infection or chemotherapy. However, the role of pyroptosis in glioma has not yet been elucidated. METHODS: RNA-seq data and clinical information of 660 gliomas and 847 samples were downloaded from the TCGA and CGGA, respectively. Then, data of 104 normal brain tissues was retrieved from the GTEx for differential expression analysis. Twelve pairs of peritumoral tissue and glioma samples were used for validation. Gene alteration status of differentially expressed pyroptosis-related regulators in gliomas was detected in cBioPortal algorithm. Consensus clustering was employed to classify gliomas based on differentially expressed pyroptosis-related regulators. Subsequently, a PS-signature was constructed using LASSO-congressional analysis for clinical application. The immune infiltration of glioma microenvironment (TME) was explored using ESTIMATE, CIBERSORT, and the other immune signatures. RESULTS: cBioPortal algorithm revealed alteration of these regulators was correlated to better prognosis of gliomas. Then, our study showed that pyroptosis-related regulators can be used to sort out patients into two clusters with distinct prognostic outcome and immune status. Moreover, a PS-signature for predicting the prognosis of glioma patients was developed based on the identified subtypes. The high PS-score group showed more abundant inflammatory cell infiltration and stronger immune response, but with poorer prognosis of gliomas. CONCLUSION: The findings of this study provide a therapeutic basis for future research on pyroptosis and unravel the relationship between pyroptosis and glioma prognosis. The risk signature can be utilized as a prognostic biomarker for glioma.

Associations Among Workplace Bullying, Resilience, Insomnia Severity, and Subjective Wellbeing in Chinese Resident Doctors.

BACKGROUND: Although workplace bullying is common among medical workers, its associations with insomnia severity and subjective wellbeing are still unclear. Our study aimed to investigate these associations among resident doctors who are more vulnerable to both workplace bullying and insomnia. METHODS: We conducted a cross-sectional survey of 1,877 resident doctors from 12 hospitals across 7 administrative regions in China. Workplace bullying, resilience, insomnia severity, and subjective wellbeing were evaluated by the Negative Acts Questionnaire-Revised (NAQ-R), the Chinese version of the Connor-Davidson Resilience Scale-10-item (CD-RISC-10), the Insomnia Severity Index, and the Index of Wellbeing, respectively. Further, a logistic regression analysis was used to analyze factors associated with insomnia. In addition, structural equation modeling (SEM) was applied to examine the associations among workplace bullying, resilience, insomnia severity, and subjective wellbeing. RESULTS: In the present study, the rates of workplace bullying and insomnia were 51.4 and 33.2%, respectively. Workplace bullying (OR = 1.056, p < 0.001) and poor resilience (OR = 0.957, p < 0.001) were the factors associated with insomnia after controlling the confounding variables. Further, SEM of the present study revealed a direct relationship between workplace bullying and subjective wellbeing (std-ß = -0.223, p < 0.001). In addition, insomnia severity (std-ß = -0.071, p < 0.001) and resilience (std-ß = -0.092, p < 0.001) can individually or collectively (std-ß = -0.008, p < 0.001) mediate the indirect associations between workplace bullying and subjective wellbeing. However, resilience was found to act as a moderator only in the direct association between workplace bullying and subjective wellbeing. CONCLUSIONS: Workplace bullying and poor resilience were the factors associated with insomnia. Further, greater resilience acted as a buffer in the direct association between workplace bullying and subjective wellbeing, whereas both insomnia severity and resilience were critical mediators in the indirect associations between them.

Bioinformatics Gene Analysis of Potential Biomarkers and Therapeutic Targets for Unstable Atherosclerotic Plaque-Related Stroke.

Atherosclerotic plaque instability is a major cause of ischemic stroke. Researchers must develop novel strategies for the detection and treatment of unstable atherosclerotic plaque (UAP)-related stroke. We aimed to identify potential biomarkers and therapeutic targets of UAP-related stroke. Differentially expressed genes (DEGs) of UAP, ischemic stroke and smoking were identified by microarray analyses from the Gene Expression Omnibus. Gene Ontology (GO) and pathway functional enrichment analyses of DEGs were performed to analyze plaque destabilization and ischemic stroke physiopathology. An integrative analysis of UAP, ischemic stroke and smoking DEGs and functional annotations was performed to identify the underlying physiopathology and hub genes in UAP-related stroke and the relationship with smoking. Online search databases were applied to confirm hub gene biofunctions and their relationships with atherosclerosis and cerebrovascular diseases. Following integrative analysis, 18 co-DEGs of UAP and ischemic stroke, including 17 upregulated and one downregulated, were identified. Inflammation, immunity, extracellular matrix degradation, blood coagulation, apoptosis and nerve degeneration were the primary physiopathological processes in UAP-related stroke. Hub genes included MMP9, ITGAM, CCR1, NCF2 and CD163, among which MMP9 and ITGAM were top 10 genes for both UAP and stroke. Smoking may upregulate MMP9, NCF2, C5AR1 and ANPEP to accelerate plaque destabilization and UAP-related stroke. MMP9, ITGAM, CCR1, NCF2, CD163, hsa-miR-3123 and hsa-miR-144-3p are potential diagnostic and prognostic biomarkers of UAP-related stroke. MMP9 and ITGAM are potential therapeutic targets of UAP-related stroke, which will contribute to the development of novel management strategies.

Selective serotonin reuptake inhibitors for functional independence and depression prevention in early stage of post-stroke: A meta-analysis.

BACKGROUND: The efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) for functional independence and depression prevention in early stage of post-stroke (within 1 month after stroke onset) are still unclear. METHODS: Relevant randomized controlled trials (RCTs) comparing early SSRIs therapy with placebo were sought from PubMed, Cochrane Library, Medline, and Embase. Primary outcomes were functional independence and depression occurrence. Secondary outcomes contained the improvement of Fugl-Meyer motor scale (FMMS) score and adverse events. We used fixed or random effects model to pooled effect estimates. And we chose risk ratio (RR) or mean differences (MDs) with the 95% confidence intervals (CIs) for data analysis. RESULTS: We included 10 RCTs with total 5370 patients. The outcome of functional independence showed no significant difference between SSRIs and placebo group (RR, 1.28; 95% CI, 0.96-1.72; P = .10; I = 92%). However, depression occurrence differed significantly between these 2 groups, which favored SSRIs group (RR, 0.78; 95% CI, 0.67-0.90; P = .001; I = 23%). In addition, we observed that the side effects of SSRIs were seizure and nausea. Except psychiatric disorders/insanity rate was less in SSRIs group than placebo group (RR, 0.66; 95% CI, 0.48-0.90; P = .009) (I = 0%), other adverse events were revealed non-significant in our meta-analysis. CONCLUSIONS: Our meta-analysis revealed that early SSRIs therapy were effective to prevent post-stroke depression. However, SSRIs did not improve patient's post-stroke functional independence. In addition to increase the occurrence of seizure and nausea, SSRIs were relatively safe.