Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank.

BACKGROUND: Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer's disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts. METHODS: This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates. RESULTS: A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels. CONCLUSIONS: These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.

Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study.

BACKGROUND: Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent. OBJECTIVE: We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure. METHODS: MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis. RESULTS: After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (p = .0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw (p = .0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw (p = .0154, beta (se) = - 9.0301 (3.7281)), cuneus THw (p = .0418, beta (se) = - 0.0020 (0.0010)), lateral orbitofrontal THw (p = .0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw (p = .0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology. CONCLUSION: Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.

Patterns of neuromyelitis optica spectrum disorder attacks in different age groups and sexes depending on the status of immunosuppressive therapy: A retrospective cohort study.

BACKGROUND AND PURPOSE: The association between onset age and sex with relapse risk in neuromyelitis optica spectrum disorder (NMOSD) remains inconclusive. We aimed to describe the clinical features of patients with NMOSD in different age groups and sexes and to analyse relapse characteristics pre- and post-immunosuppressive therapy (IST). METHODS: Patients with NMOSD were retrospectively reviewed from our clinical centre's database. Demographic and clinical data, attack presentation, and disease course pre- and post-IST were investigated. We also analysed the effect of onset age on the annualized relapse rate and relapse risk according to sex and IST status. Interactions on the additive scale between onset age and sex were analysed. A restricted cubic spline was used to analyse potential nonlinear correlations. Longitudinal changes in the Expanded Disability Status Scale score across NMOSD attacks were analysed using linear mixed-effect models. RESULTS: In total, 533 patients experienced 1394 attacks pre-IST and 753 relapses post-IST. Older age at onset was correlated with more myelitis attacks but fewer optic neuritis attacks, with no sex-related differences in attack presentation. Pre-IST, relapse risk increased with age at onset in women, while a U-shaped correlation between onset age and relapse risk was found in men. Post-IST, an inverted U-shaped association between the predicted relapse risk and onset age was observed in women. Conversely, a negative correlation between the predicted relapse risk and onset age was found in men. Overall, a higher ratio of myelitis attacks was found post-IST. CONCLUSIONS: Patients of different onset ages and sexes had different relapse patterns before and after IST.

Granzyme B + CD8 + T cells with terminal differentiated effector signature determine multiple sclerosis progression.

BACKGROUND: Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing-remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. METHODS: Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. RESULTS: Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy. CONCLUSIONS: Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS.

Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants.

BACKGROUND: Familial clustering of neuromyelitis optica spectrum disorder (NMOSD) was present in Chinese. This study was to investigate the clinical characteristics and genetic background of familial NMOSD. METHODS: Through questionnaires in four medical centres in 2016-2020, we identified 10 families with NMOSD aggregation. The statistical differences of clinical characteristics between familial and sporadic NMOSD (22 cases and 459 cases) were summarised. The whole-exome sequencing (WES) for seven families (13 cases and 13 controls) was analysed, compared with our previous WES data for sporadic NMOSD (228 cases and 1 400 controls). The family-based and population-based association and linkage analysis were conducted to identify the pathogenetic genes, the variant impacts were predicted. RESULTS: The familial occurrence was 0.87% in Chinese. Familial patients had higher expanded disability status scale score than sporadic patients (p=0.03). The single-nucleotide polymorphism (SNP) rs2252257 in the promoter and enhancer of ubiquitin-specific peptidase USP18 was linked to familial NMOSD (p=7.8E-05, logarithm of the odds (LOD)=3.1), SNPs rs361553, rs2252257 and rs5746523 were related to sporadic NMOSD (p=1.29E-10, 3.45E-07 and 2.01E-09, respectively). Patients with the SNP rs361553 T/T genotype had higher recurrence rate than C/T or C/C genotype (1.22±0.85 vs 0.69±0.57 and 0.81±0.65, p=0.003 and 0.001, respectively). SNPs rs361553 and rs2252257 altered USP18 expression in brain and nerve tissues. CONCLUSION: Most clinical characteristics of familial NMOSD were indistinguishable from sporadic NMOSD except for the worst episodes severity. USP18 with impaired intronic regulatory function contributed to the pathogenesis of NMOSD.

Brain structural and functional connectivity alterations are associated with fatigue in neuromyelitis optica spectrum disorder.

BACKGROUND: Many patients with neurological disorders experience chronic fatigue, but the neural mechanisms involved are unclear. OBJECTIVE: Here we investigated whether the brain structural and functional connectivity alterations were involved in fatigue related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: This prospective pilot study used structural and resting-state functional brain magnetic resonance imaging to compare total cortical thickness, cortical surface area, deep gray matter volume and functional connectivity (FC) between 33 patients with NMOSD and 20 healthy controls (HCs). Patients were subgrouped as low fatigue (LF) and high fatigue (HF). RESULTS: HF patients scored higher on the Hamilton Anxiety Rating Scale and Hamilton Rating Scale for Depression than LF patients and HCs. The two patient subgroups and HC group did not differ significantly in cortical thickness, cortical surface area and volumes of the bilateral caudate nucleus, bilateral putamen, bilateral amygdala, bilateral hippocampus, bilateral thalamus proper or right nucleus accumbens (p > 0.05). However, after correcting for age, sex, years of education, anxiety and depression, HF patients showed larger left pallidum than HCs (0.1573 ± 0.0214 vs 0.1372 ± 0.0145, p = 0.009). Meanwhile, both LF patients (0.0377 ± 0.0052 vs 0.0417 ± 0.0052, p = 0.009) and HF patients (0.0361 ± 0.0071 vs 0.0417 ± 0.0052, p = 0.013) showed smaller left nucleus accumbens than HCs.. Compared with LF patients, HF patients showed significantly decreased FC between the left pallidum and bilateral cerebellar posterior lobes. CONCLUSIONS: This was the first evidence linking structural and functional alterations in the brain to fatigue in NMOSD, and in the future, long term follow-up was necessary.

Translation, cross-cultural adaptation, and validation of the chinese version of the 15-item myasthenia gravis quality of life questionnaire.

INTRODUCTION: We sought to translate, cross-culturally adapt, and evaluate the internal consistency and validity of the Chinese version of the 15-Item Myasthenia Gravis Quality of Life (MG-QOL15). METHODS: Translation and cross-cultural adaptation of the MG-QOL15 were performed. We used Cronbach's α to test internal consistency, one-way analysis of variance to test construct validity, and Pearson or Spearman correlations to test discriminant and concurrent validity. RESULTS: We enrolled 168 outpatients. Internal consistency was excellent (Cronbach's α = 0.928). The MG-QOL15 discriminated MG severity as stratified by the MG Composite (MGC; P < 0.001) and Osserman class (P = 0.01). Concurrent validity was low to moderate with the subscales of the 36-item Short Form (-0.31 to ∼-0.59), MGC (r = 0.46), and Myasthenia Gravis Activities of Daily Living profile (r = 0.54). DISCUSSION: The Chinese MG-QOL15 showed comparable construct, discriminant and concurrent validity, and internal consistency with to the original version. Muscle Nerve 59:95-99, 2019.

[Anxiety and Depression in Patients with Neuromyelitis Optica].

OBJECTIVE: To assess anxiety and depression in patients with neuromyelitis optica (NMO). METHODS: Eligible patients with NMO were assessed with Hamilton anxiety rating scale-14 (HARS-14),Hamilton depression rating scale-21 (HDRS-21) and expanded disability status scale (EDSS). RESULTS: A total of 65 NMO patients [(39.85±10.36) yr., male/female: 5/60) participated in this study. They had a median EDSS score of 2.5 and a mean score of (37.37±20.44) for bodily pain. About 76.9% of patients were NMO-IgG seropositive. The participants had (11.03±6.95) HARS-14 scores and (11.74±7.78) HDRS-21 scores,with 27.69% (18/65) being diagnosed with anxiety and 24.62% (16/65) being depressed. The EDSS scores were correlated with HARS-14 scores (r=0.285, P=0.004) and HDRS-21 scores (r=0.328, P=0.008). Bodily pain was negatively correlated with HARS-14 scores (r=-0.561, P<0.001) and HDRS-21 scores (r=-0.496, P<0.001). Relapse was correlated with anxiety (r=0.285, P=0.022). Age,sex,duration of disease,and serum NMO-IgG were not correlated with HARS-14 scores and HDRS-21 scores. The logistic regression model identified bodily pain as a predictor of anxiety and depression in NMO patients (OR=1.052,1.046,respectively P<0.05). CONCLUSION: Disability and bodily pain are associated with anxiety and depression in NMO patients,while relapse is associated with anxiety only. Bodily pain is a predictor of anxiety and depression in NMO patients.

[Correlates of Fatigue in Patients with Neuromyelitis Optica].

OBJECTIVES: To determine clinical characteristics associated with fatigue in patients with neuromyelitis optica (NMO). METHODS: A questionnaire survey was conducted in NMO patients, measuring fatigue using the fatigue impact scale (FIS). RESULTS: A total of 64 NMO patients (mean age: 50.0 years; male/female: 3/61) completed the survey: 71.9% were NMO-IgG seropositive and 43 (67.2%) received immunosuppressive treatments. The patients obtained a global FIS score of 64.8±36.1, with 13.2±8.5, 20.6±11.6 and 31.0±18.7 for the cognitive, physical and social dimensions, respectively. No significant differences were found in global FIS scores ( P=0.294 9), and cognitive ( P=0.467 1), physical ( P=0.472 2) and social ( P=0.212 6) dimensional scores between those with and without immunosuppressive treatments. Age, sex, serum NMO-IgG, duration of disease and annual relapse rates were neither correlated with global FIS scores ( P>0.05), nor with the three dimensional scores ( P>0.05). The Expanded Disability Status Scale score was positively associated with global FIS scores ( P=0.000 5)and cognitive( P=0.018 7), physical( P=0.000 4) and social ( P=0.000 5)dimensional scores. The frequency of attack was also positively correlated with cognitive dimensional scores ( P=0.007 9). CONCLUSIONS: Disability is associated with cognitive, physical and social dimensions of fatigue. High frequency of attack is positively correlated with the cognitive dimension of fatigues.

Clinical features and prognosis of Tibetan patients with neuromyelitis optica spectrum disorder are different from those of Han Chinese patients.

We compared the prognosis of Tibetan and Han Chinese patients with neuromyelitis optica spectrum disorder (NMOSD). The Expanded Disability Status Scale (EDSS) score at each attack, response to immunosuppressive therapy, risk of first relapse, severe attack, visual disability, motor disability, and total risk of disability were compared between Tibetan and Han Chinese patients. Tibetan patients showed higher EDSS during acute attacks. Annualized relapse rate did not differ between groups. Risk of severe attack, visual disability, and total risk of disability were higher in Tibetan patients. Tibetan patients with NMOSD have a higher risk of poor prognosis than Han Chinese patients.

Causal effects of gut microbiota on multiple sclerosis: A two-sample Mendelian randomization study.

BACKGROUND: Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear. OBJECTIVE: We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS. METHODS: Independent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome-wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: After inverse-variance-weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021-1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007-1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688-0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585-0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634-0.940, p = .010). CONCLUSION: Our MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota-mediated MS.

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers.

Infertility affects approximately 10-15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called 'idiopathic male infertility.' Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

Integrating genetic and proteomic data to elucidate the association between immune system and blood-brain barrier dysfunction with multiple sclerosis risk and severity.

BACKGROUND: Immune system dysfunction and blood-brain barrier (BBB) impairment are implicated in multiple sclerosis (MS) risk and severity. However, the causal relationships and potential therapeutic targets remain unclear. METHODS: Leveraging the MRC IEU OpenGWAS data infrastructure, we extracted 1254 peripheral immune systems and 792 BBB biomarkers as genetic instruments for exposure. MS risk data from the International Multiple Sclerosis Genetics Consortium (IMSGC) (47,429 MS cases, 68,374 controls) served as one outcome, replicated in FinnGen (1048 cases, 217,141 controls) and the UK Biobank (1679 cases, 461,254 controls). Genetic associations with MS severity derived from IMSGC and MultipleMS Consortium GWAS data (12,584 cases). Two-sample, bidirectional, and protein drug-target MR analyses were conducted, along with interaction analysis of identified proteins and druggability assessment. RESULTS: Causal relationships between 45 immunological markers, 15 BBB markers, and MS risk were strongly supported. In peripheral immunity, the causal associations with MS are predominantly concentrated in CD4+ T cells and CD8+ T cells. Notably, anti-Epstein-Barr virus nuclear antigen (EBNA) IgG levels exhibited the most significant causal effect on MS risk (OR = 225.62, P = 5.63E-208), replicated in the MS severity (OR = 1.11, P = 0.04). Weak causal evidence was found between 62 immunological markers, 35 BBB markers, and MS severity. Reverse MR analysis suggested potential causal effects of MS risk on 8 markers. Drug-targeted MR analysis indicated potential therapeutic benefits in reducing MS risk for CD40 (OR = 0.71, P = 7.24E-13, PPH4 = 97.6 %), AHSG (OR = 0.88, P = 2.91E-05, PPH4 = 94.4 %), and FCRL3 (Sun BB et al.: OR = 0.83, P = 8.93E-09, PPH4 = 94.2 %, Suhre K et al.: OR = 0.88, P = 5.20E-08, PPH4 = 99.2 %). CONCLUSIONS: This study provides evidence supporting the causal effects of immune system and BBB dysfunction on MS risk and severity. It emphasizes the significant role of anti-EBNA IgG levels, CD4+ T cells, and CD8+ T cells in MS, and delineates the potential therapeutic benefits of targeting three proteins associated with MS risk: CD40, AHSG, and FCRL3.

Case Report: Long segmental lesions of the spinal cord caused by exposure to xylene.

Xylene has the potential to cause nervous system disturbances since it is a lipophilic substance with high affinity for lipid-rich tissue, such as the brain. Involvement in the spinal cord, especially long segmental spinal cord lesions that permeate almost the entire cervical and thoracic spinal cord, is extremely rare. We report two cases of occupational exposure to excessive xylene, both of which presented with severe and rapidly progressive numbness and weakness in the limbs that, more importantly, led to poor outcomes: one died and the other was left severely disabled. In both, spinal magnetic resonance imaging showed long segmental lesions in the cervicothoracic spinal cord. These findings may provide some insights into the effects of xylene as an isolated agent on the spinal cord injury.

Impact of swiping direction on the interaction performance of elderly-oriented smart home interface: EEG and eye-tracking evidence.

Introduction: Smart home technology is increasingly popular, yet not all seniors are receptive and comfortable with it. This situation recognizes that the usability of smart home interfaces is particularly important. Most studies on interface swiping direction demonstrate the advantages of horizontal over vertical swiping, but the findings lack age-based as well as gender-specific judgments. Methods: In this paper, we use cognitive neural techniques of EEG and eye-tracking, combined with a subjective preference questionnaire, to analyze the preference of older persons for the swiping direction of smart home interfaces in a multimodal manner. Results: The EEG data showed that swiping direction had a significant effect on potential values (p = 0.001). Also, the mean power in the δ and the θ band was enhanced during vertical swiping. Gender had no significant effect on potential values (p = 0.085), but the cognitive task was more EEG stimulating for females. The eye-tracking metrics data showed a significant effect of swiping direction on fixation duration (p = 0.047) and a non-significant effect on pupil diameter (p = 0.576). These results were consistent with the results of the subjective preference questionnaire, both demonstrating a preference for vertical swiping among participants. Discussion: This paper uses three research tools simultaneously, combining objective perceptions as well as subjective preferences, to make the findings more comprehensive and reliable. Gender differences were also taken into account and differentiated in the data processing. The findings of this paper are different from most previous studies and better reflect the preference of elderly people for swiping directions, which can provide a reference for the future elderly-friendly smart home interface design.

Initial BMI effects on clinical presentation and prognosis in neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate the correlation among body mass index at onset, clinical features, and prognosis in patients with neuromyelitis optica spectrum disorder. METHOD: This retrospective cohort studied patients with neuromyelitis optica spectrum disorder from January 2015 to January 2022, grouping them by body mass index at onset. Demographics and clinical records were reviewed. Anderson-Gill, Kaplan-Meier, and Cox models evaluated the body mass index's effect on relapse risk and long-term outcomes. RESULTS: Of 246 patients with 799 neuromyelitis optica spectrum disorder attacks study, 36 patients had low, 133 had normal, 77 had high body mass index, with a mean onset age of 40 ± 13 years, and the population was 88% female. The medium follow-up time was 49 months; AQP4-IgG was found in 193 (78%) patients. Onset and relapse of area postrema syndrome were less frequent in patients with a normal body mass index. The annual relapse rate after immunosuppressive therapy was significantly lower in patients with a low body mass index. In the multivariable analysis, statistical correlation still existed between body mass index at onset and risk of relapse (HR = 1.03, 95% CI: 1.03-1.03, P < 0.001), risk of severe attack (HR = 0.92, 95% CI: 0.86-0.98, P = 0.013), risk of visual disability (HR = 0.9, 95% CI: 0.81-1, P = 0.047), and overall risk of disability (HR = 0.89, 95% CI: 0.82-0.98, P = 0.015) after adjusting various variables. INTERPRETATION: Lower body mass index at onset was associated with less frequent relapse but poor prognosis.