The Current Status and Trends of Research Related to Vestibular Disorders, Vertigo, and Cognitive Impairment in the Elderly Population: A Bibliometric Analysis.

Background: The vestibular system not only supports reflex function at the brainstem level, but is also associated with higher levels of cognitive function. Vertigo due to vestibular disorders may lead to or be associated with cognitive dysfunction. Patients with deficits of both vestibular as well as cognitive function may be at particularly high risk for events like falls or certain diseases, such as Alzheimer's. Objective: To analyze the current state of research and trends in the global research literature regarding the correlation between vestibular disorders, vertigo, and cognitive impairment. Methods: We utilized Bibliometrix package to search databases including PubMed, Web of Science, etc for search terms. Results: Databases were searched up to December 15, 2022, and a total of 2222 publications were retrieved. Ultimately, 53 studies were included. A total of 261 authors published in 38 journals and conferences with an overall increasing annual growth rate of 6.94%. The most-published journal was Frontiers in Neurology. The most-published country was the United States, followed by Italy and Brazil. The most-published institution was Johns Hopkins University with a total of 13 articles. On performing trend analysis, we found that the most frequent focus of research in this field include the testing of vestibular perception, activation of the brain-related cortex, and the influence of stimulus-triggered vestibular snail reflex on visual space. The potential focal points are the risk of falling and the ability to extract spatial memory information, and the focus of research in recent decades has revolved around balance, falling, and Alzheimer's disease. Conclusions: Vestibular impairment in older adults affects cognitive function, particularly immediate memory, visuospatial cognition, and attention, with spatial cognition being the most significantly affected. In the future, virtual reality-based vestibular rehabilitation techniques and caloric stimulation could be potential interventions for the treatment of cognitive impairment.

U-shaped association between sleep duration and biological aging: Evidence from the UK Biobank study.

Previous research on sleep and aging largely has failed to illustrate the optimal dose-response curve of this relationship. We aimed to analyze the associations between sleep duration and measures of predicted age. In total, 241,713 participants from the UK Biobank were included. Habitual sleep duration was collected from the baseline questionnaire. Four indicators, homeostatic dysregulation (HD), phenoAge (PA), Klemera-Doubal method (KDM), and allostatic load (AL), were chosen to assess predicted age. Multivariate linear regression models were utilized. The association of sleep duration and predicted age followed a U-shape (All p for nonlinear <0.05). Compared with individuals who sleep for 7 h/day, the multivariable-adjusted beta of ≤5 and ≥9 h/day were 0.05 (95% CI 0.03, 0.07) and 0.03 (95% CI 0.02, 0.05) for HD, 0.08 (95% CI 0.01, 0.14) and 0.36 (95% CI 0.31, 0.41) for PA, and 0.21 (95% CI 0.12, 0.30) and 0.30 (95% CI 0.23, 0.37) for KDM. Significant independent and joint effects of sleep and cystatin C (CysC) and gamma glutamyltransferase (GGT) on predicted age metrics were future found. Similar results were observed when conducting stratification analyses. Short and long sleep duration were associated with accelerated predicted age metrics mediated by CysC and GGT.

Association of dietary inflammatory potential, dietary oxidative balance score and biological aging.

BACKGROUND & AIMS: The interaction between diet, inflammation, and oxidative stress significantly influences aging, but the available evidence has been limited. We evaluated potential associations of dietary inflammatory index (DII), dietary oxidative balance score (DOBS), and measures of biological aging. METHODS: This cross-sectional study was performed among 8839 individuals from NHANES 2003-2014. DII and DOBS were determined by aggregating data from 26 to 17 a priori selected dietary components. Biological aging metrics included homeostatic dysregulation (HD), Klemera-Doubal method (KDM), phenotypic age (PA), and allostatic load (AL). Binomial logistic regression models and multivariate linear regression models were conducted. RESULTS: The associations of dietary inflammation and oxidative stress potential and biological aging metrics were significant among American adults nationwide. Consuming foods with higher DII was significantly associated with accelerated HD 1.26 (1.10, 1.44), KDM 1.24 (1.06, 1.45), and PA 1.54 (1.33, 1.78). Compared with the lowest DOBS, the hazard ratios of accelerated HD, KDM, PA, and AL were 0.74 (0.64, 0.86), 0.80 (0.70, 0.92), 0.61 (0.52, 0.72) and 0.78 (0.63, 0.97), respectively. The adverse effects of pro-inflammatory and pro-oxidative diets on accelerated HD, KDM, and PA were 1.39 (1.18, 1.62), 1.28 (1.08, 1.51), and 1.76 (1.47, 2.10). Serum AST/ALT ratio and globulin were implicated in and mediate the aging effects. CONCLUSIONS: Higher DII and/or lower DOBS are associated with higher markers of biological aging. Our research elucidates that diets may mitigate biological aging resulting from inflammation and/or oxidative stress.

Hereditary Hearing Loss: A Systematic Review of Potential Treatments and Interventions.

PURPOSE: The purpose of this study was to systematically review the research literature with regards to treatments and intervention methods for hereditary hearing loss. Our goal was to provide reference guidelines for the rational use of medication and gene-targeted therapy for patients with hereditary hearing loss and discuss the future development of research in this area. METHOD: We searched two core databases, PubMed and Web of Science, for relevant literature relating to potential treatments and interventional methods for hereditary hearing loss. Then, we used Microsoft Excel to perform basic statistical analysis of the data, the R language to perform bibliometric analyses, and VOSviewer and CiteSpace to visualize data. In addition, we clustered and descriptively analyzed the data and identified the relative importance of each approach with regard to precise patient outcomes. RESULTS: In this study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standardized screening process and identified a total of 103 research articles. The average annual growth rate of publications in this area was 12.73%. The country with the highest number of publications and citations was the United States; 80 of these publications (associated with 76.92% of funding) were supported by grants from 16 countries. Potential treatments and interventions were clustered according to the stage of research and showed that 8.74% remain in the research design stage, 59.22% are in the clinical validation stage, and 32.04% are being applied in the clinic. The main research focus in this field is cochlear implants and gene therapy. CONCLUSIONS: Hereditary hearing loss is in a critical period of transition from preventive to therapeutic research. Gene-targeted interventions represent one of the most promising and effective treatments. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24309193.

Current Status and Trends in mHealth-Based Research for Treatment and Intervention in Tinnitus: Bibliometric and Comparative Product Analysis.

BACKGROUND: As a global medical problem, tinnitus can seriously harm human health and is difficult to alleviate, ranking among the top 3 complex diseases in the otolaryngology field. Traditional cognitive behavioral therapy and sound therapy require offline face-to-face treatment with medical staff and have limited effectiveness. Mobile health (mHealth), which, in recent decades, has been greatly applied in the field of rehabilitation health care, improving access to health care resources and the quality of services, has potential research value in the adjunctive treatment of tinnitus. OBJECTIVE: This study aimed to understand the research trends, product characteristics, problems, and research transformation of tinnitus treatment software by analyzing the research progress of mHealth for tinnitus treatment based on the literature and related marketed apps. METHODS: Bibliometric methods were used to describe the characteristics of the relevant literature in terms of the number and topics of publications, authors, and institutions. We further compared the features and limitations of the currently available tinnitus treatment software. RESULTS: Data published until February 28, 2022, were collected. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standardized screening process, 75 papers were included. The country with the highest number of publications was Germany, followed by the United Kingdom and the United States, whereas China had only a single relevant study. The most frequently found journals were the American Journal of Audiology and the Journal of the American Academy of Audiology (18/75, 24%). With regard to publication topics, cognitive behavioral therapy started to become a hot topic in 2017, and research on mHealth apps has increased. In this study, 28 tinnitus treatment apps were obtained (n=24, 86% from product data and n=4, 14% from literature data); these apps were developed mainly in the United States (10/28, 36%) or China (9/28, 32%). The main treatment methods were sound therapy (10/28, 36%) and cognitive behavioral therapy (2/28, 7%). Of the 75 publications, 7 (9%) described apps in the market stage. Of the 28 apps, 22 (79%) lacked literature studies or evidence from professional bodies. CONCLUSIONS: We found that, as a whole, the use of mHealth for treatment and intervention in tinnitus was showing a rapid development, in which good progress had been made in studies around sound therapy and cognitive behavioral therapy, although most of the studies (50/75, 67%) focused on treatment effects. However, the field is poorly accepted in top medical journals, and the majority are in the research design phase, with a lack of translation of the literature results and clinical validation of the marketed apps. Furthermore, in the future, novel artificial intelligence techniques should be used to address the issue of staged monitoring of tinnitus.

Genomic Analysis of an Escherichia coli Sequence Type 167 Isolate Harboring a Multidrug-Resistant Conjugative Plasmid, Suggesting the Potential Transmission of the Type Strains from Animals to Humans.

Purpose: The E. coli ST167 clone is the globally dominant ST among extraintestinal pathogenic E. coli (ExPEC) and is frequently associated with carbapenem resistance. This study reports genomic characterization of a pandrug-resistant E. coli ST167 isolate (ECO3183) and the possibility of the type strains' transmission. Materials and Methods: Antibiotic susceptibility testing was performed using disk diffusion and the VITEK 2 automated system. The E. coli ECO3183 genome was sequenced. We used the genome to analyze the phylogenetic relationship, phylogenetic group, sequence type (ST), acquired antibiotic resistance genes (ARGs), IS elements, genomics islands, the replicon type and transferability of the plasmids. The conjugative transfer of plasmids was assessed using filter mating experiments. Results: ECO3183 contained a 4.87-Mb chromosome and two plasmids [pECO3183-1 (167.63 Kb) and pECO3183-2 (46.16 Kb)]. It belonged to phylogenetic group A, clonal complex 10 (CC10), and ST167. ECO3183 is a pandrug-resistant strain nonsusceptible to 24 tested antimicrobials representing 8 different antimicrobial classes. Among 55 E. coli isolates phylogenetically related to ECO3183, 47% (26/55) were from humans, while 35% (19/55) were from animals. Further analysis revealed that among 1140 ST167 isolates (in the EnteroBase database), 4% (47/1140) originated from environments, 17% (192/1140) were isolated from humans, and 78% (890/1140) were obtained from animals. The pECO3183-1 contained two identical repeats of a 9633 bp region (IS6100-sul1-ΔaadA16-dfrA27-arr-3-aac(6')-Ib-cr-IS26) and a 17.88-kb resistance island (sul2-aph(3″)-Ib-aph(6)-Id-IS26-Δaph(3')-Ia-IS26-tet(A)-ΔfloR-ΔISVsa3-IS26-Δaac(3)-IId-IS26-mph(A)), and these three regions contained most of ECO3183 carrying ARGs. It was identified as a conjugative plasmid, which confers MDR resistance and has the potential to spread. Conclusion: ECO3183 exhibited pandrug-resistance phenotype that was mediated by pECO3183-1 carrying MDR ARGs and pECO3183-2 carrying blaNDM-5. Source analysis of strains indicated that ST167 E. coli might be transmitted between species from animals to humans, which needs continued monitoring.

Causal associations of histidine and 12 site-specific cancers: a bidirectional Mendelian randomization study.

An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.

Global research trends in benign paroxysmal positional vertigo: a bibliometric analysis.

Background: Benign paroxysmal positional vertigo is the most common disease in which vertigo is the main clinical manifestation, and it has become a global medical problem, affecting a wide range of areas and seriously affecting the quality of human life. Objective: This article presents an analysis of the current characteristics of BPPV-related research and summarizes the current hot topics and trends, with the goal of inspiring future research into the prevention and treatment of BPPV, thereby improving the differential diagnosis and prevention of peripheral vertigo. Methods: A bibliometric approach was used to collect 1,219 eligible studies on BPPV from four databases-PubMed, Embase, Scopus, and Web of Science-published between 1974 and 2022. The characteristics and status of the accumulated scientific output were processed using R and VOSviewer so that we could visualize any trends or hotspots. Results: The results showed a significant increase in the annual number of publications, with an average annual growth rate of 21.58%. A possible reason for the especially pronounced peak in 2021 was an increase in the prevalence of BPPV as a result of COVID-19. The new coronavirus became a focus of research in 2021. A total of 3,876 authors (of whom 1,097 were first authors) published articles in 307 different journals; 15.7% of the articles were published in Acta Oto-Larygologica, Otology and Neurotology, and Frontiers in Neurology. Acta Oto-Laryngologica was well ahead of the other journals in terms of growth rate and number of articles published. American scholars generated the largest number of articles overall, and the USA was involved in the greatest number of international collaborations, followed by Italy and China. The themes of the research centered around three topics, namely the treatment of BPPV, its influencing factors, and diagnosis. Conclusions: There has been a major increase in BPPV-related research over the last 50 years, leading to an increase in related articles and rapid development of the field. Key directions for future research include the improvement of individualized treatment for residual symptoms after initial treatment of BPPV among the elderly; effective control of comorbidities such as osteoporosis; and secondary inner ear disease, such as Ménière's disease.

MicroRNA-23a-3p Is Upregulated in Plasma Exosomes of Bulbar-onset ALS Patients and Targets ERBB4.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease related to the progressive death of motor neurons. Understanding the pathogenesis of ALS continues to provide considerable challenges. Bulbar-onset ALS involves faster functional loss and shorter survival time than spinal cord-onset ALS. However, debate is ongoing regarding typical plasma miRNA changes in ALS patients with bulbar onset. Exosomal miRNAs have not yet been described as a tool for bulbar-onset ALS diagnosis or prognosis prediction. In this study, candidate exosomal miRNAs were identified by small RNA sequencing using samples from patients with bulbar-onset ALS and healthy controls. Potential pathogenic mechanisms were identified through enrichment analysis of target genes for differential miRNAs. Expression of miR-16-5p, miR-23a-3p, miR-22-3p, and miR-93-5p was significantly up-regulated in plasma exosomes from bulbar-onset ALS patients compared with healthy control subjects. Among them, miR-16-5p and miR-23a-3p were significantly lower in spinal-onset ALS patients than those with bulbar-onset. Furthermore, up-regulation of miR-23a-3p in motor neuron-like NSC-34 cells promoted apoptosis and inhibited cell viability. This miRNA was found to directly target ERBB4 and regulate the AKT/GSK3ß pathway. Collectively, the above miRNAs and their targets are related to the development of bulbar-onset ALS. Our research indicates that miR-23a-3p might have an effect on motor neuron loss observed in bulbar-onset ALS and may be a novel target for the therapy of ALS in the future.

The influence of "small private online course + flipped classroom" teaching on physical education students' learning motivation from the perspective of self-determination theory.

Objective: The study aimed to enhance the learning motivation of college physical education students and improve their learning outcomes. Based on the perspective of the self-determination theory, this study explores the influence of "Small Private Online Course (SPOC) + flipped classroom" teaching on the learning motivation of students majoring in physical education and profoundly analyzes the influencing factors and promotion paths of learning motivation using this model. Materials and methods: A total of four classes (64 students) of physical education majors in a university were selected and randomly divided into an experimental group (34 students) and a control group (30 students). The experimental group received "SPOC + flipped classroom" teaching, the control group received traditional teaching. Before and after the 16-week intervention, learning motivation, teacher support perception, basic psychological need satisfaction, and academic emotions of the 64 students were measured, and the data were analyzed by repeated-measures analysis of variance and partial least square regression. Results: (1) The instructional intervention reduced non-regulation, external regulation, and introjected regulation, while increased identified regulation, intrinsic regulation, and self-determination levels in the students. The levels of non-regulation, external regulation, identified regulation, and self-determination were also significantly different from those of the control group. (2) After the intervention, the scores of support for autonomy, support for competence, support for relatedness, and need for relatedness in the experimental group were significantly higher than those in the control group. (3) Support for autonomy, support for competence, support for relatedness, need for competence and need for relatedness positively predicted the self-determination level, and intrinsic regulation and identified regulation negatively predicted non-regulation, external regulation, and introjected regulation. Conclusion: "SPOC + flipped classroom" teaching has a positive impact on students' learning motivation of basketball skills and promotes students' motivation autonomy. The improvement of support for autonomy, support for competence, support for relatedness, need for competence, and need for relatedness may be related to the improvement of learning motivation of college students majoring in Physical Education (PE). "SPOC + flipped classroom" teaching enables students to obtain more demand satisfaction by giving them more demand support, while demand support and demand satisfaction can promote the internalization of learning motivation so that students can maintain high autonomy motivation.

Causal Relationships Between Relative Intake from the Macronutrients and Alzheimer's Disease: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Some observational studies indicated the associations of relative carbohydrate, sugar, fat, and protein intake and Alzheimer's disease (AD). But it remains unclear whether the associations are causal. OBJECTIVE: This study aimed to identify the effects of relative carbohydrate, sugar, fat, and protein intake in the diet on AD. METHODS: A two-sample Mendelian randomization was employed. Finally, 14 independent lead SNPs remained in the Social Science Genetic Association Consortium. These SNPs of relative carbohydrate, sugar, fat, and protein intake at the level of genome-wide significance (p < 5×10-8) were used as instrumental variables. The summary data for AD were acquired from the International Genomics of Alzheimer's Project with a total of 54,162 individuals (17,008 AD patients and 37,154 control participants). RESULTS: This two-sample Mendelian randomization indicated that increased relative protein intake (per 1 standard deviation) causally decreased the AD risk (OR = 0.48, 95% CI: 0.24-0.95, p = 0.036), and increased relative fat intake may decrease the risk of AD (OR = 0.22, 95% CI: 0.06-0.86, p = 0.029). No statistical significance with AD risk was seen for relative carbohydrate or relative sugar intake. CONCLUSION: A higher relative intake of protein can causally reduce the risk of AD in the elderly. Additionally, a higher relative intake of fat may be protective against AD. No evidence showed that AD was associated with relative carbohydrate and sugar intake.

The dynamic expression of canonical Wnt/ß-catenin signalling pathway in the pathologic process of experimental autoimmune neuritis.

Background: Guillain-Barré syndrome (GBS), an autoimmune disease and an acute inflammation disorder, is currently the most frequent cause of acute flaccid paralysis worldwide. EAN, an animal model of GBS, is a CD4+ T cell-mediated autoimmune disease of the PNS. Wnt/ß-catenin signals are critically important to several fundamental aspects of peripheral nerve development and play a crucial role in Schwann cell proliferation. Here, we investigate the role of Wnt/ß-catenin signalling cascades in EAN rats.Methods: 28 male Lewis rats weighing 170 ± 10 g were randomly divided into control group (n = 7) and EAN groups (Early group; Peak group and Recovery group. n = 7 per group). EAN rats were immunized with P257-81 peptide; weighed daily, and the neurologic signs of EAN were evaluated every day. The sciatic nerve was taken on the days 10, 17, and 30 p.i. for H&E staining, transmission electron microscopy and immunohistochemical staining; blood samples were collected weekly from caudal vein to detect IFN-γ, IL-4, TGF-ß1; and the sciatic nerve was taken to examinate the dynamics expression of Wnt/ß-catenin pathway molecules.Results: In our study, we chose tail-root injection to better model GBS. Moreover, we observed that IFN-γ levels paralleled clinical EAN, and the levels of TGF-ß1 and IL-4 gradually increased and peaked in the recovery phase. In addition, we have shown that canonical Wnt signalling is upregulated and reached a peak in the late recovery phase.Conclusion: Our findings suggest that Wnt/ß-catenin signalling is associated with the promotion of remyelination in EAN rats.

Th17 cells and their cytokines serve as potential therapeutic target in experimental autoimmune neuritis.

BACKGROUND: Accumulating evidence has pointed that T helper 17 cells and their cytokines are pathogenic in Guillain-Barré syndrome (GBS). However, little is known concerning the IL-17 expression change trend during the whole course of disease, and whether drugs specially targeting Th17 cells or their cytokines have potential effects on experimental autoimmune neuritis (EAN) is uncertain. METHODS: We explored the IL-17 and receptor-related orphan receptor-gamma-t (RORγt) expression change trends in EAN rats to identify the stage of effect of Th17 pathway in EAN, and further, we investigated the effect of RORγt inhibitors by assessing clinical score, histological staining, and IL-17 and RORγt expression change trends in serum and tissues. RESULTS: The expression level of IL-17 and RORγt in serum and tissues increased with the progression of the disease in the EAN group and decreased after the disease reaching its peak. RORγt-IN-1 treatment strikingly reduced the neurological deficits by ameliorating inflammatory cell infiltration, deceased the serum IL-17 and RORγt levels, and further downregulated the expression of IL-17 and RORγt mRNA in spleen, lymphnodes, and sciatic nerve. CONCLUSIONS: Th17 cells and their cytokines are closely associated with the onset of GBS and the novel RORγt inhibitors may be prospective strategies in treating GBS.