Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood-brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood-brain barrier function.

Statistical and network analyses reveal mechanisms for the enhancement of macrophage immunity by manganese in Mycobacterium tuberculosis infection.

Tuberculosis is a significant infectious disease that poses a serious risk to human health. Our previous research has indicated that manganese ions reduce the bacterial load of Mycobacterium tuberculosis in macrophages, but the exact immune defense mechanism remains unknown. Several critical proteins and pathways involved in the host's immune response during this process are still unidentified. Our research aims to identify these proteins and pathways and provide a rationale for the use of manganese ions in the adjuvant treatment of tuberculosis. We downloaded GSE211666 data from the GEO database and selected the RM (Post-infection manganese ion treatment group) and Ra (single-infection group) groups for comparison and analysis to identify differential genes. These differential genes were then enriched and analyzed using STRING, Cytoscape, and NDEx tools to identify the two most relevant pathways of the "Host Response Signature Network." After conducting an in-depth analysis of these two pathways, we found that manganese ions mainly mediate (1) the interferon -gamma (IFN-γ) and its receptor IFNGR and the downstream JAK-STAT pathway and (2) the NFκB pathway to enhance macrophage response to interferon, autophagy, polarization, and cytokine release. Using qPCR experiments, we verified the increased expression of CXCL10, MHCII, IFNγ, CSF2, and IL12, all of which are cytokines that play a key role in resistance to Mycobacterium tuberculosis infection, suggesting that macrophages enter a state of pro-inflammatory and activation after the addition of manganese ions, which enhances their immunosuppressive effect against Mycobacterium tuberculosis. We conclude that our study provides evidence of manganese ion's ability to treat tuberculosis adjuvantly.

Mismatch of MRI White Matter Hyperintensities and Gait Function in Patients With Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is closely related to gait disorders. Previous studies have found a negative correlation between the severity of MRI white matter hyperintensities (WMH) and gait speed. However, not every individual with WMH experiences a gait disorder. PURPOSE: To investigate the mechanisms underlying the mismatch between the severity of MRI WMH and gait impairment, in particular in subjects with severe WMH (Fazekas 3, scale 0-3) resulting from vascular disease. STUDY TYPE: Cohort. POPULATION: 54 subjects with severe WMH and gait disorder (WMH-GD; 29 males) and 114 subjects with severe WMH with no gait disorder (WMH-nGD; 60 males). FIELD STRENGTH/SEQUENCE: 3T/diffusion tensor imaging (DTI), and T1-weighted, T2-weighted, FLAIR, DWI, SWI. ASSESSMENT: Trace-based spatial statistics analysis (TBSS) approach (fractional anisotropy, FA; mean diffusivity; radial diffusivity; axial diffusivity); Cognitive assessment; Conventional MRI markers of CSVD (WMH, enlarged perivascular spaces, lacunae, and cerebral microbleeds); Gait parameters (gait speed; cadence; stride length; gait cycle duration; step duration; time-up-and-go test, TUG). Gait disorder was defined as a TUG time exceeding 12 sec. STATISTICAL TESTS: The t-tests, Mann-Whitney U tests, Chi-square tests, and partial correlation analysis (Pearson or Spearman) were used. P < 0.05 with threshold-free cluster enhancement corrected was considered statistically significant for TBSS. RESULTS: After adjusting for age, sex, height, and other conventional MRI markers of CSVD, the WMH-nGD group showed significantly decreased FA values in the corpus callosum, bilateral superior longitudinal fasciculus, left corona radiata, and left posterior thalamic radiation. There was a significant association between FA values and TUG time, gait speed, and stride length in multiple WM tracts, independent of other conventional CSVD markers. DATA CONCLUSION: This study provides evidence for microstructural damage of specific fibers in WMH-GD subjects compared to WMH-nGD subjects. This may explain the mismatch between WMH and gait impairment in subjects with severe WMH. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Type A personality, sleep quality, and cerebral small vessel disease: investigating the mediating role of sleep in a community-based study.

Purpose: Type A behavior pattern (TABP) is a personality type characterized by rapid speech, impatience, competition, and hostility. Asymptomatic cerebral small vessel disease (CSVD) is often endemic in older adults. Individuals with TABP commonly experience suboptimal sleep quality, and a correlation exists between sleep disturbances and CSVD. We investigated the relationship between TABP and CSVD markers and further explored the mediating role of sleep quality in the relationship between TABP and CSVD. Methods: A cross-sectional survey included 764 community-dwelling adults aged 55-85 years. The TABP Scale and the Pittsburgh Sleep Quality Index (PSQI) were used to assess personality and sleep quality, respectively. Linear and logistic regression analyses were used to examine relationships between variables of interest. In addition, mediation analyses with bootstrapping were used to test whether sleep quality mediated the relationship between TABP and CSVD. Results: Of the 764 participants [median age 65 (61-69) years, 59.9% female], the population with type A personality accounted for 44.8%. After adjusting for covariates, TABP scores (p = 0.03) and PSQI scores (p < 0.001) were significantly correlated with CSVD. In addition, sleep quality partially mediated the association between type A behavior and CSVD, and the mediating effect was 10.67%. Conclusion: This study showed that type A behavior was a risk factor for CSVD among older community-dwelling adults and that sleep quality mediated the relationship between type A behavior and CSVD. Changing type A behavior may help improve sleep quality, which may in turn reduce the prevalence of CSVD.

Asymmetry of Lacunae between Brain Hemispheres Is Associated with Atherosclerotic Occlusions of Middle Cerebral Artery.

Cerebral small vessel disease (CSVD) commonly coexists with intracranial atherosclerotic stenosis (ICAS). Previous studies have tried to evaluate the relationship between ICAS and CSVD; however, they have yielded varied conclusions. Furthermore, the methodology of these studies is not very rigorous, as they have evaluated the association between ICAS and CSVD of bilateral hemispheres rather than the affected hemisphere. Unilateral middle cerebral artery atherosclerotic occlusion (uni-MCAO) is a favorable model to solve this problem. MATERIAL AND METHODS: Patients with uni-MCAO were retrospectively observed. Imaging characteristics, including lacunae, white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs), were compared between the hemisphere ipsilateral to the MCAO and the contralateral hemisphere. RESULTS: A total of 219 patients (median age 57 years; 156 males) were enrolled. Compared with the contralateral side, increased quality of lacunae (median, IQR, 0, 2 vs. 0, 1; p < 0.001) and elevated CSVD score (median, IQR, 0, 1 vs. 0, 1; p = 0.004) were found in the occluded hemisphere. No significant differences were shown for WMH, EPVS, and CMBs. CONCLUSIONS: Uni-MCAO has a higher prevalence of lacunae in the ipsilateral hemisphere. However, no interhemispheric differences in WMH, EPVS, or CMBs were found.

Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study.

Introduction: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. Evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i), effectively lowers low-density lipoprotein (LDL) and produces favorable changes in coronary atherosclerosis. This study aimed to determine the effects of PCSK9i on intracranial plaques in moderate-intensity statin-treated individuals with ICAS. Methods: This prospective, observational study monitored the imaging and clinical outcomes of individuals with ICAS who were consecutively treated with moderate-intensity statins with or without PCSK9i. Individuals underwent monthly visits and repeat high-resolution MRI (HR-MRI) at week 12. The primary outcome was a change in HR-MRI after 12 weeks of treatment and the secondary outcome was major vascular events during follow-up. Results: Forty-nine individuals were studied (PCSK9i group: 26 individuals with 28 abnormal vascular regions; statin group: 23 with 27 regions). The PCSK9i group showed a significant reduction in the normalized wall index (0.83 vs. 0.86, p = 0.028) and stenosis degree (65.5 vs. 74.2%, p = 0.01). Similarly, a greater percentage of individuals with a good response to the efficacy of treatment were treated in the PCSK9i group than that in the statin group (75 vs. 44.4%, p = 0.021). The incidence of major vascular events was overall similar between the groups. The treatment options (OR = 8.441, p = 0.01) and prior diabetes (OR = 0.061, p = 0.001) were significantly associated with the efficacy of treatment. Discussion: Statin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI. Further study is warranted to determine if combination treatment improves clinical outcomes in ICAS.

Effect of Cerebral Small Vessel Disease Burden on Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment.

Background: Cerebral small vessel disease (SVD) is common in the aging population. The study aimed to evaluate the effect of SVD on functional outcomes in patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT). Methods: From a prospective registry, we selected patients with AIS receiving EVT. SVD features, including white matter hyperintensities (WMH), lacunes and brain atrophy, were assessed on MRI and a validated SVD score was calculated to reflect the total SVD burden. Results: Among 137 patients included, 106 had none-mild SVD burden and 31 had moderate-severe SVD burden. The moderate-severe SVD burden group showed a significantly higher modified Rankin Scale score at 90 d (median, 4 versus 1 points, adjusted common odds ratio 0.32 [95% CI, 0.14-0.69], P < 0.01) and a significantly smaller improvement of NIHSS at 24 h (median, -3 versus -3 points, adjusted ß coefficient 4.02 [95% CI, 0.57-7.48], P = 0.02) and 7 days (median, -4 versus -6 points, adjusted ß coefficient 4.71 [95% CI, 1.06-8.36], P = 0.01) than the none-mild group. There was no significant difference in successful recanalization, death within 90 days, symptomatic intracranial hemorrhage within 24 h between two groups (all P > 0.05). Additionally, for each single SVD feature, brain atrophy and WMH, but not lacunes, were associated with the functional outcome. Conclusion: Moderate-severe SVD burden was associated with poor early and late functional outcomes in patients with AIS receiving EVT. Our results suggest that SVD score may act as a good predictor of outcomes in these patients.

Abnormalities of retinal structure and microvasculature are associated with cerebral white matter hyperintensities.

BACKGROUND AND PURPOSE: Whilst retinal microvasculature represents cerebral small vessels, the retinal nerve fiber layer is the extended white matter of the brain. The aim was to investigate the correlation between changes in retina and white matter hyperintensities (WMHs). METHODS: Sixty-four candidates with WMHs received an optical coherence tomography angiography examination. WMHs were divided into mild or moderate/severe groups according to the Fazekas score. After imaging the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the microvascular density parameters (vascular perfusion density [VPD], vascular length density [VLD] and fovea avascular zone area) and morphological parameters (vessel diameter index [VDI], fractal dimension [FD] and vessel tortuosity) were identified. A software algorithm measured the thickness of the peripapillary retina nerve fiber layer (PRNFL). RESULTS: Thirty-two were classified as having mild WMHs and 32 were moderate/severe. The median (interquartile range) ages of the two groups were 58 (54-64) and 61 (57-67) years, respectively. A decrease of FD, VPD and VLD in either SCP or DCP appeared with an increased risk of moderate/severe WMHs. Although changes of capillary plexus were not associated with paraventricular WMHs, decreased FD, VPD, VLD and fovea avascular zone area in either SCP or DCP were associated with an increased risk of moderate/severe deep WMHs (DWMHs). Participants with moderate/severe WMHs demonstrated reduced PRNFL thickness, particularly in the DWMHs, compared with mild WMHs. CONCLUSIONS: Abnormalities of retinal microvascular density, morphological parameters and PRNFL thickness are correlated with the incidence of moderate/severe WMHs, particularly the DWMHs, suggesting that arteriosclerosis and hypoperfusion are the causes of DWMHs.

Association of Excessive Daytime Sleepiness with Cerebral Small Vessel Disease in Community-Dwelling Older Adults.

Purpose: Excessive daytime sleepiness (EDS) and cerebral small vessel disease (CSVD) are common problems among older adults; however, their association is not clear. The present study aimed to investigate the frequency of EDS in CSVD patients and the relationship between EDS and neuroimaging markers of CSVD. Patients and Methods: We conducted a cross-sectional study among 1076 community-dwelling older adults aged 55-85 years. EDS was measured using the Epworth Sleepiness Scale (ESS), and EDS was defined as an ESS score greater than 10. Binary logistic regression was performed to assess the association between EDS and neuroimaging markers of CSVD. Results: Of the 1076 participants (mean age: 65.58 ± 6.46 years, 60.5% female), the prevalence of EDS was 10.0%. EDS was more frequent in participants with CSVD than in the total sample (20.0% vs 10.0%, p <0.001). In fully adjusted models, EDS was significantly correlated with CSVD burden (OR = 1.39, 95% CI 1.16 to 1.68, p <0.001), the severity of white matter hyperintensities (WMH) (OR = 1.33, 95% CI 1.14 to 1.54, p <0.001), and presence of lacunes (OR = 2.47, 95% CI 1.53 to 4.00, p <0.001) but not with the presence of cerebral microbleeds (CMBs) (OR=1.54, 95% CI 0.92 to 2.56, p = 0.099) or severity of enlarged perivascular spaces (EPVS) in basal ganglia (OR = 1.16, 95% CI 0.70 to 1.92, p = 0.564). Conclusion: We found a high frequency of EDS symptoms in CSVD individuals. Further, EDS was significantly associated with WMH, lacunes, and CSVD burden. Our findings further suggest patients with CSVD may exhibit abnormal sleep-wake patterns.

Triglyceride-Glucose Index and the Risk of Stroke: A Systematic Review and Dose-Response Meta-Analysis.

Insulin resistance (IR) is an independent risk factor of cardiovascular disease. Recent research has proposed a new inexpensive and reliable indicator of IR: triglyceride glucose index (TyG index). We aim to evaluate the dose-response association between the TyG index and stroke through meta-analysis. Literature published from inception until October 2021 were searched in PubMed, Embase, Cochrane Library and Web of science. Cohort studies published in English and focusing on the association between the TyG index and stroke were included in our meta-analysis. I2 statistic and Chi-square were used to assess the heterogeneity. When I2≥30% or p≤0.10, the random-effect model was used to pool the effect; otherwise, we chose the fixed-effect model. Eleven cohort studies, including 5 721 077 subjects and 95 490 stroke patients, were included in our study. After pooling the effect adjusted by multiple confounders, we found that compared with the lowest baseline TyG index group, the highest one was independently associated with increased stroke risk (RR: 1.27; 95% CI, 1.24 to 1.29; I2=6%). Dose-response meta-analysis showed that the association between the two variables had a non-linear trend (p-nonlinearity<0.0001; p-heterogeneity=0.28). Subgroup analysis showed that the risk of ischemic stroke was positively correlated with TyG index (RR: 1.48; 95% CI, 1.34 to 1.62; I2=15%), while we did not observe this correlation in hemorrhagic stroke patients. In patients with type 2 diabetes and acute coronary syndrome, the TyG index was linearly correlated with incident strokes. In conclusion, elevated TyG index is the independent risk factor for incident strokes (especially ischemic stroke).

Thromboelastography predicts dual antiplatelet therapy-related hemorrhage in patients with acute ischemic stroke.

BACKGROUND: Stratification of the risk of hemorrhage in patients with acute ischemic stroke following dual antiplatelet therapy (DAPT) is challenging. It remains unclear whether thromboelastography (TEG) can be used to predict DAPT-related hemorrhagic events. OBJECTIVE: The present study aims to discover predictors for hemorrhage events after DAPT based on parameters such as TEG. METHODS: A total of 859 patients with acute ischemic stroke who received DAPT were recruited consecutively. Demographic, clinical, and neuroimaging characteristics were evaluated at baseline; TEG parameters were obtained 7 days later after DAPT. Hemorrhagic events were monitored about 1 month after the stroke. RESULTS: Of the patients, 61 (7.1%) had hemorrhagic events. Patients in the hemorrhage group had a lower adenosine diphosphate (ADP)-induced platelet-fibrin clot maximum amplitude and a higher ADP inhibition rate (ADP%) than those in the non-hemorrhage group (p<0.05). ADP% was confirmed as an independent predictor of hemorrhagic events with an optimal cut-off point of 83.3% (area under the curve (AUC) = 0.665, 95% CI 0.573 to 0.767, p<0.01). We constructed a logistic model based on D-dimer, National Institutes of Health Stroke Scale scores, and ADP% to predict hemorrhagic events in patients with acute ischemic stroke during DAPT (AUC=0.720, 95% CI 0.625 to 0.858, p<0.01), with a sensitivity of 72.1% and a specificity of 76.5%. CONCLUSIONS: Monitoring changes of TEG parameters helps to guide personalized DAPT for patients with ischemic stroke. A 30-82.3% range of ADP% is recommended for DAPT treatment.

Sleep Quality Mediates the Association Between Cerebral Small Vessel Disease Burden and Frailty: A Community-Based Study.

Background: Physical frailty is a common problem among older adults which usually leads to adverse health outcomes. The imaging markers of cerebral small vessel disease (CSVD) are associated with frailty, but the underlying mechanisms remain unclear. The present study aimed to investigate the mediating role of sleep quality in the relationship between CSVD burden and frailty. Methods: We performed a cross-sectional study and enrolled community residents. Frailty and sleep quality were measured using the Fried frailty phenotype and the Pittsburgh Sleep Quality Index (PSQI), respectively. A multivariate linear regression analysis and a Bootstrap analysis were performed to examine the association among the key variables and the mediating role of sleep quality. Results: Of the 726 participants (mean age: 65.5 ± 6.5 years, 59.8% female), the numbers (percentages) of the frail, prefrail, and robust residents were 49 (6.7%), 310 (42.7%), and 367 (50.6%), respectively. After adjusting for covariates, the CSVD burden and PSQI score were significantly associated with the frailty score. In addition, sleep quality played a partial mediating role in the association between CSVD burden and physical frailty. The mediating effect was 21.9%. Conclusion: The present study suggests that sleep quality is a mediator of this association between CSVD and frailty in community-dwelling older adults. Improving sleep quality might be helpful to mitigate the risk of frailty in CSVD patients.

Impact of Diabetes on Platelet Function in Acute Ischemic Stroke Patients Taking Dual Antiplatelet Therapy.

Objectives: Diabetes mellitus (DM) is a significant risk factor for ischemic stroke and associated with platelet reactivity. We aim to evaluate the effect of DM on platelet function in acute ischemic stroke patients taking dual antiplatelet therapy (DAPT). Methods: We consecutively included patients with acute ischemic stroke taking DAPT. Platelet function was assessed by thromboelastography and the arachidonic acid (AA) or adenosine diphosphate (ADP) induced platelet inhibition rate were used to confirmed the high-residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel. We classified patients into DM and non-DM groups. The association between DM and platelet function was assessed and the confounding factors were adjusted by propensity score matching (PSM) analysis. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. Results: A total of 1,071 acute ischemic stroke patients, 712 in the non-DM group and 359 in the DM group, were included. Patients with DM had a significantly higher maximum amplitude (63.0 vs. 62.0 mm, P < 0.01), ADP-induced clot strength (34.6 vs. 30.3 mm, P < 0.01) and clopidogrel HRPR rate (22.6% vs. 17.3%, P = 0.038) than those without DM. Among 662 patients after PSM, the maximum amplitude (63.1 vs. 62.5 mm, P = 0.032), ADP-induced clot strength (34.6 vs. 29.3 mm, P < 0.01) and clopidogrel HRPR rate (23.0% vs. 15.7%, P = 0.018) is still higher in the DM group. DM was an independent factor of clopidogrel HRPR (OR = 1.48, 95% CI: 1.03-2.07, P < 0.05). Conclusions: In acute ischemic stroke patients taking DAPT, DM is associated with increased platelet reactivity and higher prevalence of clopidogrel HRPR.

Treatment of the Carotid In-stent Restenosis: A Systematic Review.

Background and Purpose: In-stent restenosis (ISR) after carotid artery stent (CAS) is not uncommon. We aimed to evaluate therapeutic options for ISR after CAS. Methods: We searched PubMed and EMBASE until November 2, 2020 for studies including the treatment for ISR after CAS. Results: In total, 35 studies, covering 1,374 procedures in 1,359 patients, were included in this review. Most cases (66.3%) were treated with repeat CAS (rCAS), followed by percutaneous transluminal angioplasty (PTA) (17.5%), carotid endarterectomy (CEA) (14.3%), carotid artery bypass (1.5%), and external beam radiotherapy (0.4%). The rates of stroke & TIA within the postoperative period were similar in three groups (PTA 1.1%, rCAS 1.1%, CEA 1.5%). CEA (2.5%) was associated with a slightly higher rate of postoperative death than rCAS (0.7%, P = 0.046). Furthermore, the rate of long-term stroke & TIA in PTA was 5.7%, significantly higher than rCAS (1.8%, P = 0.036). PTA (27.8%) was also associated with a significantly higher recurrent restenosis rate than rCAS (8.2%, P = 0.002) and CEA (1.6%, P < 0.001). The long-term stroke & TIA and recurrent restenosis rates showed no significant difference between rCAS and CEA. Conclusions: rCAS is the most common treatment for ISR, with low postoperative risk and low long-term risk. CEA is an important alternative for rCAS. PTA may be less recommended due to the relatively high long-term risks of stroke & TIA and recurrent restenosis.

Triglyceride glucose index influences platelet reactivity in acute ischemic stroke patients.

AIM: Insulin resistance was reported to increase the risk of ischemic stroke, which can be assessed by the triglyceride glucose (TyG) index. However, it remains unclear whether the TyG index influences the platelet reactivity during the treatment of ischemic patients. METHODS: Ischemic stroke patients receiving dual antiplatelet therapy (DAPT) within 48 h onset were consecutively included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The top quartile of TyG index was defined as insulin resistance. The platelet reactivity was assessed by thromboelastography. The platelet inhibition rate induced by arachidonic acid (AA) or adenosine diphosphate (ADP) was used to confirm the high residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel, respectively. The association between TyG index and platelet reactivity was assessed by Kruskal-Wallis test. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. RESULTS: A total of 1002 patients were included and divided into 4 groups by quartiles of the TyG index (< 2.02; 2.02-2.27; 2.27-2.52; ≥2.52). The findings demonstrated that the maximum intensity of the clot increased, but the AA-induced platelet inhibition rate decreased, depending on the TyG index quartiles. No significant difference was found in the ADP-induced platelet inhibition rate among groups. The prevalence of aspirin HRPR increased depending on the TyG index quartile. Unlike the non-insulin resistance group, the insulin resistance group was independently associated with aspirin HRPR (OR = 1.689, 95% CI 1.14 to 2.51, P = 0.009). CONCLUSIONS: In acute ischemic stroke patients taking DAPT, the elevation of the TyG index is associated with enhanced platelet reactivity and higher prevalence of aspirin HRPR. Insulin resistance assessed by the TyG index could be an independent risk factor for aspirin HRPR.

Serum Cortisol Is Associated With Cerebral Small Vessel Disease-Related Brain Changes and Cognitive Impairment.

OBJECTIVE: To evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance. METHODS: We recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4. RESULTS: In total, 158 participants were included in this study with a mean age of 60.5 (56.0-66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively. CONCLUSIONS: Serum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD.

Endovascular treatment for ischemic stroke beyond the time window: A meta-analysis.

Currently, endovascular treatment has been proven to be effective when conducted within 6 hours of symptom onset. However, when patients have symptoms for more than 6 hours, have a daytime-unwitnessed stroke (DUS) or wake up with a stroke (wake-up stroke, WUS), the safety and efficacy of endovascular treatment need to be further elucidated. Therefore, we performed a systematic review and meta-analysis to compare the clinical outcomes of endovascular treatment in patients with ischemic stroke beyond the time window with that ≤6 hours. PubMed, EMBASE, and Ovid MEDLINE were searched from inception to November 2018. The following outcomes were evaluated by a random-effects model: efficacy outcomes, that is, functional independence and successful recanalization, and safety outcomes, that is, symptomatic intracranial hemorrhage and mortality. Subgroup analyses were also performed to examine whether patient or study characteristics were associated with the outcomes. Nine observational studies, including 5192 patients (1414 patients with extended time windows [ETWs]; 3778 patients ≤6 hours), were eligible for analysis. The overall analysis demonstrated that the functional independence was worse in patients with ETWs vs those ≤6 hours (OR, 0.78; 95% CI, 0.68-0.90, P = .0006). However, subgroup analysis showed that there was no significant difference in functional independence between the two groups when patients were selected for a perfusion mismatch by imaging (OR, 1.00; 95% CI, 0.70-1.43, P = 1.000). Therefore, compared with a window ≤6 hours, endovascular treatment with ETWs for ischemic stroke may not result in poor outcomes when patients are typically selected by perfusion techniques.

Evolution of cooperation driven by self-recommendation.

Cooperators increase the fitness of others at a cost to themselves. Thus cooperation should not be favored by natural selection in a well-mixed population. It challenges the evolutionists since cooperation is widespread. Information spreading has been revealed to play a key role in the emergence of cooperation. Individuals, however, are typically assumed to be passive in the information spreading. Here we assume that individuals self-recommend themselves to those that are about to have new neighbors. Individuals with higher tendencies of self-recommendation are likely to have more neighbors. In this way, individuals are active to spread the information. We analytically obtain a critical cost-to-benefit ratio, below which cooperation emerges. It reveals quantitatively how eloquent cooperators have to be compared with defectors to ensure that cooperation takes over the population. It also indicates that individuals need to be open enough to the self-recommendation to enhance cooperation level. In addition, the critical cost-to-benefit ratio represents the viscosity of the population, measuring how close cooperators are to each other. Our results highlight the role self-recommendation plays in cooperation.

Porous nanorods of nickel-cobalt double hydroxide prepared by electrochemical co-deposition for high-performance supercapacitors.

Nickel-cobalt double hydroxides (Ni-Co DHs) combined with cost-effectively commercial expanded graphite (EG) was prepared via a facile in-situ electrodeposition in mixed solvents of N,N-dimethylformamide and water. By simply adjust molar ratios of Ni2+/Co2+, a Ni-Co DHs/EG electrode in which Ni-Co DHs showing a porous-nanorod microstructure was fabricated. Thanks to synergistic effects between Ni(OH)2 and Co(OH)2 as well as the unique morphology of porous nanorods, an optimal Ni-Co DHs/EG electrode with a total mass loading of 4.0 mg cm-2 can deliver a specific capacitance of 1246 F g-1 at 1 A g-1, a rate capability of 91.8% as the discharging current density increasing from 1 to 10 A g-1, and a capacitance retention of 80.1% after 1000 cycles charged/discharged at 10 A g-1. Thus we can draw a conclusion that the Ni-Co DHs/EG electrode possesses a satisfactory specific capacitance, extremely superior rate performance, and good cycle stability, therefore it can be very competitive for practical applications in supercapacitors.