The effect of aperiodic components in distinguishing Alzheimer's disease from frontotemporal dementia.

Distinguishing between Alzheimer's disease (AD) and frontotemporal dementia (FTD) presents a clinical challenge. Inexpensive and accessible techniques such as electroencephalography (EEG) are increasingly being used to address this challenge. In particular, the potential relevance between aperiodic components of EEG activity and these disorders has gained interest as our understanding evolves. This study aims to determine the differences in aperiodic activity between AD and FTD and evaluate its potential for distinguishing between the two disorders. A total of 88 participants, including 36 patients with AD, 23 patients with FTD, and 29 healthy controls (CN) underwent cognitive assessment and scalp EEG acquisition. Neuronal power spectra were parameterized to decompose the EEG spectrum, enabling comparison of group differences in different components. A support vector machine was employed to assess the impact of aperiodic parameters on the differential diagnosis. Compared with the CN group, both the AD and FTD groups showed varying degrees of increased alpha power (both periodic and raw power) and theta alpha power ratio. At the channel level, theta power (both periodic and raw power) in the frontal regions was higher in the AD group compared to the FTD group, and aperiodic parameters (both exponents and offsets) in the frontal, temporal, central, and parietal regions were higher in the AD group than in the FTD group. Importantly, the inclusion of aperiodic parameters led to improved performance in distinguishing between the two disorders. These findings highlight the significance of aperiodic components in discriminating dementia-related diseases.

Smoking and alcohol consumption with the risk of 11 common otolaryngological diseases: a bidirectional Mendelian randomization.

PURPOSE: In this study, a bidirectional mendelian randomization was applied to evaluate the association of smoking and alcohol consumption with 11 otolaryngological diseases. METHODS: A total of 85,22,34 and 7 single nucleotide polymorphisms were used as instrumental variables for smoking initiation, cigarettes per day, alcoholic drinks per week and alcohol consumption, respectively. Genetic associations with 11 common otolaryngological diseases were obtained from the UK Biobank and FinnGen dataset. IVW, weighted median, MR-Egger, MR-PRESSO and leave-one-out method were used in this analysis. RESULTS: Smoking initiation increased the risk of vocal cord and larynx diseases (OR 1.002; 95% CI 1.001-1.004; P = 4 × 10-4), head and neck cancer (OR 1.001; 95% CI 0.999-1.003; P = 0.027), thyroid cancer (OR 1.538; 95% CI 1.006-2.351; P = 0.047) and sleep apnoea (OR 1.286; 95% CI 1.099-1.506; P = 0.002). Cigarettes per day was associated with chronic sinusitis (OR 1.152; 95% CI 1.002-1.324; P = 0.046), chronic rhinitis and pharyngitis (OR 1.200; 95% CI 1.033-1.393; P = 0.017), vocal cord and larynx diseases (OR 1.001; 95% CI 0.999-1.002; P = 0.021) and head and neck cancer (OR 1.001; 95% CI 0.999-1.003; P = 0.017). Alcoholic drinks per week only was significantly associated with the risk of head and neck cancer (OR 1.003; 95% CI 1.001-1.006; P = 0.014). However, there was no evidence to support that genetically predicted alcohol consumption increased the risk of otolaryngological diseases. Reverse MR also did not find outcomes effect on exposures. CONCLUSION: This study shows that smoking and heavy alcohol consumption promote the occurrence of some otolaryngological diseases indicating that lifestyle modification might be beneficial in preventing otolaryngological diseases.

Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats.

AIM: Parkinson's disease (PD) is a pervasive neurodegenerative disease, and levodopa (L-dopa) is its preferred treatment. The pathophysiological mechanism of levodopa-induced dyskinesia (LID), the most common complication of long-term L-dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non-dopaminergic systems contribute to LID development. As a 5-hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L-dopa administration and the potential mechanism of eltoprazine's amelioration of dyskinesia at the electrophysiological level in rats. METHODS: Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity. RESULTS: We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia. CONCLUSION: Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.

The Gut Microbiota and Inflammatory Factors in Pediatric Appendicitis.

Background: The study analyzed gut microflora's composition and investigated the associations between the associations between gut dysbiosis and inflammatory indicators in pediatric patients with acute appendicitis. Methods: High-throughput sequencing and bioinformatics analysis were used to investigate the composition and diversity of gut microflora in 20 pediatric patients with acute appendicitis and 11 healthy children. Endpoints measured were operational taxonomic units (OTU) of gut microflora. The OTU and its abundance analysis, sample diversity analysis, principal component analysis of samples, differential analysis, and analysis of biomarkers were performed. Results: Overall fecal microbial richness and diversity were similar in patients and controls. Yet richness within the group of Bilophila, Eggerthella, Clostridium, Parvimonas, Megasphaera, Atopobium, Phascolarctobacterium, Adlercreutzia, Barnesiella, Klebsiella, Enterococcus, and Prevotella genera was higher in patients. Adlercreutzia was significantly positively correlated with IL-10, while the three other genera, comprising Klebsiella, Adlercreutzia, and Prevotella, were positively correlated with B cells level. Conclusion: Gut microbiome components are significantly different in pediatric patients with acute appendicitis and healthy children. The differential abundance of some genera is correlated with the production of inflammatory markers in appendicitis.

Identification of PBK as a hub gene and potential therapeutic target for medulloblastoma.

Medulloblastoma (MB) is the most frequent malignant brain tumor in pediatrics. Since the current standard of care for MB consisting of surgery, cranio­spinal irradiation and chemotherapy often leads to a high morbidity rate, a number of patients suffer from long­term sequelae following treatment. Targeted therapies hold the promise of being more effective and less toxic. Therefore, the present study aimed to identify hub genes with an upregulated expression in MB and to search for potential therapeutic targets from these genes. For this purpose, gene expression profile datasets were obtained from the Gene Expression Omnibus database and processed using R 3.6.0 software to screen differentially expressed genes (DEGs) between MB samples and normal brain tissues. A total of 282 upregulated and 436 downregulated DEGs were identified. Functional enrichment analysis revealed that the upregulated DEGs were predominantly enriched in the cell cycle, DNA replication and cell division. The top 10 hub genes were identified from the protein­protein interaction network of upregulated genes, and one identified hub gene [PDZ binding kinase (PBK)] was selected for further investigation due to its possible role in the pathogenesis of MB. The aberrant expression of PBK in MB was verified in additional independent gene expression datasets. Survival analysis demonstrated that a higher expression level of PBK was significantly associated with poorer clinical outcomes in non­Wingless MBs. Furthermore, targeting PBK with its inhibitor, HI­TOPK­032, impaired the proliferation and induced the apoptosis of two MB cell lines, with the diminished phosphorylation of downstream effectors of PBK, including ERK1/2 and Akt, and the activation of caspase­3. Hence, these results suggest that PBK may be a potential prognostic biomarker and a novel candidate of targeted therapy for MB.

MRI radiomic features of peritumoral edema may predict the recurrence sites of glioblastoma multiforme.

Background and purpose: As one of the most aggressive malignant tumor in the central nervous system, the main cause of poor outcome of glioblastoma (GBM) is recurrence, a non-invasive method which can predict the area of recurrence pre-operation is necessary.To investigate whether there is radiological heterogeneity within peritumoral edema and identify the reproducible radiomic features predictive of the sites of recurrence of glioblastoma(GBM), which may be of value to optimize patients' management. Materials and methods: The clinical information and MR images (contrast-enhanced T1 weighted and FLAIR sequences) of 22 patients who have been histologically proven glioblastoma, were retrospectively evaluated. Kaplan-Meier methods was used for survival analysis. Oedematous regions were manually segmented by an expert into recurrence region, non-recurrence region. A set of 94 radiomic features were obtained from each region using the function of analyzing MR image of 3D slicer. Paired t test was performed to identify the features existing significant difference. Subsequently, the data of two patients from TCGA database was used to evaluate whether these features have clinical value. Results: Ten features with significant differences between the recurrence and non-recurrence subregions were identified and verified on two individual patients from the TCGA database with pathologically confirmed diagnosis of GBM. Conclusions: Our results suggested that heterogeneity does exist in peritumoral edema, indicating that the radiomic features of peritumoral edema from routine MR images can be utilized to predict the sites of GBM recurrence. Our findings may further guide the surgical treatment strategy for GBM.

The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated. Due to its genetic mutations and downregulated expression in patients with ASD, EPHB6, which also plays important roles in gut homeostasis, is generally considered a candidate gene for ASD. Nonetheless, the role and mechanism of EPHB6 in regulating the gut microbiota and the development of ASD are unclear. RESULTS: Here, we found that the deletion of EphB6 induced autism-like behavior and disturbed the gut microbiota in mice. More importantly, transplantation of the fecal microbiota from EphB6-deficient mice resulted in autism-like behavior in antibiotic-treated C57BL/6J mice, and transplantation of the fecal microbiota from wild-type mice ameliorated the autism-like behavior in EphB6-deficient mice. At the metabolic level, the disturbed gut microbiota in EphB6-deficient mice led to vitamin B6 and dopamine defects. At the cellular level, the excitation/inhibition (E/I) balance in the medial prefrontal cortex was regulated by gut microbiota-mediated vitamin B6 in EphB6-deficient mice. CONCLUSIONS: Our study uncovers a key role for the gut microbiota in the regulation of autism-like social behavior by vitamin B6, dopamine, and the E/I balance in EphB6-deficient mice, and these findings suggest new strategies for understanding and treating ASD. Video abstract.