RESUMO
BACKGROUND: Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. METHODS AND RESULTS: We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). CONCLUSIONS: Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.
Assuntos
Viscosidade Sanguínea , AVC Isquêmico , Substância Branca , Humanos , Feminino , Masculino , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/fisiopatologia , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética , Leucoencefalopatias/sangue , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/fisiopatologia , Leucoencefalopatias/etiologia , Sístole , Fatores de Risco , Idoso de 80 Anos ou mais , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/fisiopatologiaRESUMO
Objectives: This study investigated the associations between several obesity-related anthropometric indices and mortality in middle-aged and elderly populations to compare the indices' predictive ability with that of the body mass index (BMI). Methods: We analyzed data on 12 indices calculated from 19,805 community-based cohort participants (average age, 63.27 years; median follow-up, 13.49 years). Each index was calculated using directly measured values of height, weight, waist circumference (WC), and hip circumference (HC). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for each index using Cox regression and evaluated mortality prediction with the Harrell c-index. Results: Adding anthropometric indices to the basic mortality model (c-index 0.7723; 95% CI, 0.7647-0.7799) significantly increased the predictive power of BMI (c-index 0.7735; 95% CI, 0.7659-0.7811), a body shape index (ABSI, c-index 0.7735; 95% CI, 0.7659-0.7810), weight-adjusted waist index (WWI, c-index 0.7731; 95% CI, 0.7656-0.7807), and waist to hip index (WHI, c-index 0.7733; 95% CI, 0.7657-0.7809). The differences between the BMI model and the other 3 models were not statistically significant. Conclusion: In predicting all-cause mortality, the ABSI, WWI, and WHI models based on WC or HC had stronger predictive power than conventional risk factors but were not significantly different from the BMI model.
RESUMO
BACKGROUND: This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). METHODS: We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. RESULTS: Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. CONCLUSION: AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.
RESUMO
PURPOSE: Drug-resistant epilepsy (DRE) poses a significant challenge in epilepsy management, and reliable biomarkers for identifying patients at risk of DRE are lacking. This study aimed to investigate the association between serum uric acid (UA) levels and the conversion rate to DRE. METHODS: A retrospective cohort study was conducted using a common data model database. The study included patients newly diagnosed with epilepsy, with prediagnostic serum UA levels within a six-month window. Patients were categorized into hyperUA (≥7.0 mg/dL), normoUA (<7.0 and >2.0 mg/dL), and hypoUA (≤2.0 mg/dL) groups based on their prediagnostic UA levels. The outcome was the conversion rate to DRE within five years of epilepsy diagnosis. RESULTS: The study included 5,672 patients with epilepsy and overall conversion rate to DRE was 19.4%. The hyperUA group had a lower DRE conversion rate compared to the normoUA group (HR: 0.81 [95% CI: 0.69-0.96]), while the hypoUA group had a higher conversion rate (HR: 1.88 [95% CI: 1.38-2.55]). CONCLUSIONS: Serum UA levels have the potential to serve as a biomarker for identifying patients at risk of DRE, indicating a potential avenue for novel therapeutic strategies aimed at preventing DRE conversion.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Ácido Úrico , Humanos , Ácido Úrico/sangue , Masculino , Feminino , Epilepsia Resistente a Medicamentos/sangue , Epilepsia Resistente a Medicamentos/diagnóstico , Adulto , Estudos Retrospectivos , Adulto Jovem , Pessoa de Meia-Idade , Epilepsia/sangue , Epilepsia/diagnóstico , Adolescente , Biomarcadores/sangue , Criança , Estudos de Coortes , Progressão da DoençaRESUMO
Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET- groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12-0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14-0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0-2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.
RESUMO
In this study, we present a novel method for controlling the growth of perovskite crystals in the vacuum thermal evaporation process by utilizing a vacuum-processable additive, propylene urea (PU). By coevaporation of perovskite precursors with PU to form the perovskite layer, PU, acting as a Lewis base additive, retards the direct reaction between the perovskite precursors. This facilitates a larger domain size and reduced defect density. Following the removal of the residual additive, the perovskite layer, exhibiting improved crystallinity, demonstrates reduced charge recombination, as confirmed by a time-resolved microwave conductivity analysis. Consequently, there is a notable enhancement in open-circuit voltage and power conversion efficiency, increasing from 1.05 to 1.15 V and from 17.17 to 18.31%, respectively. The incorporation of a vacuum-processable and removable Lewis base additive into the fabrication of vacuum-processed perovskite solar cells offers new avenues for optimizing these devices.
RESUMO
Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.
Assuntos
Doença de Alzheimer , Doença Hepática Induzida por Substâncias e Drogas , Panax , Camundongos , Animais , Tacrina/farmacologia , Tacrina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase/metabolismo , Farmacologia em Rede , Proteínas Quinases Ativadas por AMP , Inibidores da Colinesterase/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controleRESUMO
Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.
RESUMO
BACKGROUND: Cerebral small vessel disease is characterized by white matter hyperintensities (WMH) and acute small vessel occlusion (SVO) stroke. We investigated the effect of prior antiplatelet use (APU) on stroke outcome in 1151 patients with acute SVO stroke patients and moderate to severe WMH. METHODS: Using a multicenter database, this retrospective study used quantitative WMH volume measurements and propensity score matching (PSM) for comparisons between patients with prior APU and without APU. Primary outcomes were stroke progression and poor functional outcome (modified Rankin Scale>2) at 3 months. Logistic regression analyses assessed associations between prior APU, WMH burden, and stroke outcomes. RESULTS: Stroke progression was lower in the prior APU group in both the total cohort (14.8% vs. 6.9%, p < 0.001) and the PSM cohort (16.3% vs. 6.9%, p < 0.001). The proportion of poor functional outcomes at 3 months was not significantly different in the total cohort, but the PSM cohort showed a lower proportion in the prior APU group (30.8% vs. 20.2%, p = 0.002). Logistic regression analysis confirmed that prior APU was associated with a reduced risk of stroke progression (OR, 0.39; 95% CI, 0.22-0.70; p = 0.001) and poor functional outcome at 3 months (OR, 0.37; 95% CI, 0.23-0.59; p < 0.001). CONCLUSION: Prior APU is associated with reduced stroke progression and improved functional outcome at 3 months in acute SVO stroke patients with moderate to severe WMH. Early treatment of WMH and acute SVO stroke may have potential benefits in improving stroke outcomes.
Assuntos
Doenças de Pequenos Vasos Cerebrais , AVC Isquêmico , Acidente Vascular Cerebral , Substância Branca , Humanos , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Substância Branca/diagnóstico por imagem , Estudos Multicêntricos como AssuntoRESUMO
Introduction: Detection of atrial fibrillation (AF) is crucial for preventing recurrence in patients with ischemic stroke. We aimed to examine whether the left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) are associated with AF in patients with ischemic stroke. Methods: We prospectively analyzed 678 consecutive patients with ischemic stroke. LAVI and GLPS were assessed using three-dimensional transthoracic echocardiography with speckle-tracking imaging. Multiple logistic regression was used to evaluate the association of AF with LAVI and GLPS. To evaluate the predictive value of LAVI and GLPS for the presence of AF, we used optimism-corrected c-statistics calculated by 100 bootstrap repetitions and the net reclassification improvement (NRI). Results: The mean patient age was 68 ± 13 years (men, 60%). Patients with AF (18%) were a higher LAVI (41.7 ml/m2 vs. 74.9 ml/m2, P < 0.001) and a higher GLPS than those without AF (-14.0 vs. -17.3, P < 0.001). Among the 89 patients classified with embolic stroke of unknown source, the probable cardioembolic group had higher GLPS (n= 17, -14.6 vs. -18.6, respectively; P= 0.014) than the other groups (n= 72). Adding GLPS to age, hypertension, and the LAVI significantly improved the NRI, with an overall NRI improvement of 6.1% (P= 0.03). Discussion: The LAVI andGLPS with speckle-tracking imaging echocardiography may help identify patients with AF.