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Objective: This study aimed to evaluate the association between ophthalmic artery (OA) Doppler indices and adverse neonatal outcomes in women with pregnancies complicated by preeclampsia (PE)., Methods: A prospective cross-sectional study involving 110 pregnant women who were diagnosed with PE in the first 24 h of hospitalization was conducted at three hospitals in southeastern Brazil from April 2020 to December 2022. The ophthalmic parameters analyzed were the resistance index (RI), pulsatility index (PI), first peak systolic velocity (PSV1), second peak systolic velocity (PSV2), ratio of PSV2 to PSV1 (PSV ratio or the peak ratio [PR]), and end-diastolic velocity (EDV). The outcome measures were neonatal death (during hospitalization), neonatal intensive care unit (ICU) admission, gestational age at delivery < 32 weeks, birth weight < 1500 g, birth weight < 10th percentile, the presence of comorbidities associated with prematurity, the use of invasive mechanical ventilation, an Apgar score at the 5th minute < 7.0, and signs of neurological impairment., Results: Pregnant women with severe features of PE showed higher values of systolic (152.8 ± 20.7 vs. 136.3 ± 11.9, p = 0.000) and diastolic (98.1 ± 12.8 vs. 88.1 ± 10.8, p = 0.000) blood pressure values and lower gestational age at admission (31.5 ± 3.8 vs. 33.7 ± 4.3, p = 0.009) than PE without severe features. No significant differences were found between the mean values of the OA Doppler indices when comparing the presence or absence of neonatal outcomes in the women with PE., Conclusions: OA Doppler, while valuable for the prediction, diagnosis, and evaluation of adverse maternal outcomes, does not independently predict adverse neonatal outcomes in women with severe features of PE., (© 2024 Wiley Periodicals LLC.)

Substance abuse disorder is a chronic condition for which pharmacological treatment options remain limited. L-type calcium channels (LTCC) have been implicated in drug-related plasticity and behavior. Specifically, dopaminergic neurons in the mesocorticolimbic pathway express Ca v 1.2 and Ca v 1.3 channels, which may regulate dopaminergic activity associated with reward behavior. Therefore, this study aimed to investigate the hypothesis that pre-administration of the LTCC blocker, isradipine can mitigate the effects of cocaine by modulating central glutamatergic transmission. For that, we administered isradipine at varying concentrations (1, 7.5, and 15 μg/μL) via intracerebroventricular injection in male Swiss mice. This pretreatment was carried out prior to subjecting animals to behavioral assessments to evaluate cocaine-induced locomotor sensitization and conditioned place preference (CPP). The results revealed that isradipine administered at a concentration of 1 μg/μL effectively attenuated both the sensitization and CPP induced by cocaine (15 mg/kg, via i. p.). Moreover, mice treated with 1 μg/μL of isradipine showed decreased presynaptic levels of glutamate and calcium in the cortex and hippocampus as compared to control mice following cocaine exposure. Notably, the gene expression of ionotropic glutamate receptors, AMPA, and NMDA, remained unchanged, as did the expression of Ca v 1.2 and Ca v 1.3 channels. Importantly, these findings suggest that LTCC blockage may inhibit behavioral responses to cocaine, most likely by decreasing glutamatergic input in areas related to addiction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis., Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis., Results: Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity., Conclusion: Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Priscila Silva Franco et al.)

Objective and Design: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model., Material: Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3)., Methods: Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis., Results: Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3., Conclusions: In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To evaluate the accuracy of different parameters of the ophthalmic artery Doppler (OAD) in the complementary diagnosis of preeclampsia (PE)., Methods: This meta-analysis adhered to the PRISMA guidelines. To investigate the mean difference in OAD values, peak systolic velocity (PSV), end-diastolic velocity (EDV), second systolic velocity peak (P2), resistance index (RI), pulsatility index (PI), and peak ratio (PR), between PE cases (overall and according to severity) and controls, random-effects meta-analyses were conducted for each Doppler parameter, with overall PE and mild and severe PE subgroups. Diagnostic performance and heterogeneity were evaluated with summary receiver operating characteristic (sROC) curves and 95% confidence intervals obtained with bivariate models., Results: Eight studies stratified the results into mild and severe or late and early PE, involving 1,425 pregnant women. PR and P2 had better diagnostic performance than the other indexes, with the PR of AUsROC at 0.885, the sensitivity of 84%, and specificity of 92%, with a low false-positive rate of 0.08 and the P2 with AUsROC of 0.926, the sensitivity of 85% and specificity of 88%. RI, PI, and EDV showed good performance and consistency across studies but lower AUsROC values of 0.833, 0.794, and 0.772, respectively., Conclusion: Ophthalmic artery Doppler is a complementary tool with good performance for the diagnosis of overall and severe preeclampsia, with high and best sensitivity and specificity when using PR and P2 parameters., (© 2023. The Author(s).)

Objectives: To calculate the accuracy (A) and establish the best cutoff value for ophthalmic artery (OA) Doppler velocimetry indexes in patients diagnosed with preeclampsia (PE), compared with healthy pregnant women., Methods: This prospective experimental study enrolled 268 women: 133 with PE and 135 healthy pregnant women. All patients were evaluated by OA Doppler sonography, bilaterally, to assess their pulsatility index (PI), resistance index (RI), peak systolic velocity (PVS), second peak systolic velocity (P2), end-diastolic velocity (EDV), and peak ratio (PR). Means were compared using Student's T -test. Receiver Operating Characteristics (ROC) curve was used to establish the cutoff value and estimate the sensitivity (S), specificity (Sp), accuracy (A) of all variables, and a significance of 95% was adopted., Results: ROC curve analysis showed that P2 and PR were superior to the other parameters for PE diagnosis. We tested two cutoff values: (1) using PR ≥0.70, obtained A: 88.72%, S: 81.95%, and Sp: 95.48% and (2) using PR ≥0.75, and A: 86.24%, S: 74.43%, and Sp: 99.24%. By adopting P2 ≥ 21.5 cm/s, we obtained A: 87.59%, S: 84.96%, and Sp: 90.22% and when the cutoff point was P2 ≥ 22 cm/s, there was a slight decrease in A to 86.46% and S to 81.20%, with Sp: 91.89.3%., Conclusion: Ophthalmic artery Doppler demonstrated to be an effective and high-performance imaging method for the diagnosis of PE and the indexes P2 and PR demonstrated superior accuracy to the other Doppler parameters assessed. Higher performance occurred when the cutoff values with greater specificity were adopted, PR ≥ 0.75 and P2 ≥ 22 cm/s, considering that the proposed OA Doppler is to be a complementary method for preeclampsia.

Vascular dysfunctions can progress and lead to stroke and cardiovascular disease, especially in smokers. The presence of particular vascular changes according to sex has been described and they can be identified by the Doppler method. This study evaluated Doppler velocimetry parameters of the Ophthalmic Artery (OA) and the Middle Cerebral Artery (MCA) according to sex in smokers regarding a non-smoker group. This cross-sectional observational study included 178 subjects: 93 women and 85 men. Doppler parameters were assessed in OA and MCA. Student's t-test was used, with p < 0.05. There were no significant differences in OA and MCA Doppler velocimetry data between male non-smokers and smokers. However, female smokers presented several differences compared with non-smokers: lower pulsatility index (PI) and higher peak ratio in OA, and higher PI and resistance index and lower end diastolic velocity in MCA. There were different brain vascular waveforms in the group of female smokers compared with non-smokers. Cigarette smoking also led to opposite arterial patterns in OA and MCA in the female group, with signs of falling impedance in OA and increased impedance in MCA. An individualized approach regarding arterial changes according to sex is desirable., (© 2021. The Author(s).)

Objectives: To evaluate ophthalmic Doppler velocimetry patterns in pregnant women with pregestational diabetes mellitus with and without retinopathy in comparison to pregnant women without gestational intercurrences., Methods: This cross-sectional observational study analyzed Doppler indices of the ophthalmic arteries, including the resistive index (RI), pulsatility index, peak systolic velocity, second peak systolic velocity, peak ratio, and end-diastolic velocity (EDV), in 3 groups of pregnant women: diabetic with retinopathy (n = 12); diabetic without retinopathy (n = 85); and nondiabetic controls (n = 122). The Kruskal-Wallis test was used for the statistical analysis with a probability of 95%., Results: The mean gestational ages ± SDs of pregnant women with and without retinopathy and nondiabetic controls were 29.1 ± 2.2, 29.7 ± 2.7, and 31 ± 1.0 weeks, respectively, with no significant differences between the groups (P > .099). The mean RI in the group with retinopathy was significantly higher (P = .030) than in the control group, but it did not significantly differ compared to the group without retinopathy (P = .204). The RI in the control group did not differ from that in the group without retinopathy (P = .079). The EDV was significantly lower in the group with retinopathy (P = .015) in relation to the control group, but there were no differences compared to the group without retinopathy (P = .217)., Conclusions: Pregnant women with pregestational diabetes mellitus and retinopathy had increased vascular impedance in the ophthalmic artery together with a reduction in the EDV, which was probably related to ischemia, thrombosis, and neovascularization of retinal vessels., (© 2020 American Institute of Ultrasound in Medicine.)

Pre-eclampsia (PE) is a severe disorder that affects up to 8% of all pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. The screening of the disease is a subject of studies, but the complexity and uncertainties regarding its etiology make this objective a difficult task. In addition, the costs related to screening protocols, the heterogeneity of the most affected populations and the lack of highly effective prevention methods reduce the potential of current available algorithms for screening. Thus, the National Specialized Commission of Hypertension in Pregnancy of the Brazilian Association of Gynecology and Obstetrics Federation (Febrasgo, in the Portuguese acronym) (NSC Hypertension in Pregnancy of the Febrasgo) considers that there are no screening algorithms to be implemented in the country to date and advocates that Aspirin and calcium should be widely used., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: The vascular endothelium has specific estrogen receptors and the impact of hormone therapy (HT) on circulation is associated with cardiovascular protection in perimenopause and postmenopause. Blood vessels can be assessed by ultrasound Doppler velocimetry, and more specifically the study of the ophthalmic artery (OA) can be used for brain vessel assessment; more recently, it is a possible method for cardiovascular risk assessment., Methods: A cross-sectional study involved perimenopausal and postmenopausal women divided into three groups: 60 non-HT users (control group), 23 users of estrogen therapy (ET group), and 23 users of estrogen-progesterone therapy (EPT group). Doppler velocimetry of the OA was performed with analysis of the resistance index (RI), pulsatility index (PI), systolic peak velocity (P1), second systolic peak velocity (P2), peak velocity ratio (PVR), final diastolic velocity (FDV), and ratio between means of systolic and diastolic velocity (SDR)., Results: There was no significant difference between the groups in Doppler velocimetry indices of the OA: RI ( p  = 0.94), PI ( p  = 0.85), P1 ( p  = 0.81), P2 ( p  = 0.53), PVR ( p  = 0.41), FDV ( p  = 0.76), and SDR ( p  = 0.84). We observed a positive correlation of the SDR with age only in the control group ( r  = 0.34, p  = 0.01)., Conclusions: There is a positive correlation between the SDR and age in the control group. Therefore, this new index is a promising instrument in the non-invasive assessment of cardiovascular risk.

Purpose of Review: Cardiovascular and endothelial dysfunction is recognized nowadays as an important etiological factor contributing to the development of hypertensive disorders of pregnancy., Recent Findings: Preeclampsia is considered a specific disease of pregnancy, but recent theories suggest that women suffering from the condition have greater propensity to develop atherosclerosis, heart disease, and stroke over the years. It is possible that transient but severe endothelial dysfunction observed in preeclampsia potentiates a cascade of events that progresses to atherosclerosis. Preeclampsia offers a unique window of opportunity to identify maternal endothelial dysfunction and pre-existing cardiovascular disease. The placenta is closely involved in the onset of preeclampsia, but endothelial and cardiac vascular factors also play important causal roles in the development of hypertension during pregnancy. According to the data presented, it is clear that preeclampsia selects a group at high risk of development of atherosclerosis and at increased cardiovascular risk, as well as of stroke, in the decades following childbirth.

In ancient times, mead was produced by fermentation of honey in water and presented low quality, undesired by-products, off-flavors, and the production was time consuming. In this study, nine experiments were performed to improve the fermentation and mead characteristics. Distillation was not part of the production process and it was performed in this work to produce a new spirit. The samples were characterized by gas chromatography coupled to mass spectrometry, high performance liquid chromatography, digital densimetry, titration, gravimetric method, pH, and refractometry. The results were compared to commercial beverages and legal limits. The meads presented high ethanol concentration, low by-products, fast fermentation, and high quality. The spirits showed high quality and the concentrations of acetic acid, ethyl acetate, methanol, higher alcohols, and ethyl carbamate were below the limits for safe consumption. In conclusion, it was possible to develop new conditions to produce high quality mead and mead spirit., (© Association of Food Scientists & Technologists (India) 2019.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The objective of this study was to analyze the relationships of osmotic and mechanical stability of erythrocytes with anthropometric, biochemical, hematologic and hemodynamic variables in pregnant women with preeclampsia (PE). The studied population consisted of 20 normotensive patients and 16 patients with PE. Patients with PE presented worse gestational outcome, greater hematologic impairment, erythrocytes osmotically more stable in vitro, but in conditions of isotonicity with the in vivo medium, in addition to hyperflow in orbital territory, when compared to normotensive patients. The correlation analysis between anthropometric, hematologic and hemodynamic variables in patients with PE indicated that erythrocytes with lower volumes and lower levels of hemoglobin favor the occurrence of a better gestational outcome, because they are more stable and because they are associated with a decrease in the hemodynamic changes present in the disease. This should mean that the tendency to microcytosis, probably due to a mechanism of compensatory mechanical selection, is a desirable characteristic in the disease., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events. One function of high-density lipoprotein (HDL) cholesterol (HDL-C) is the cholesterol-efflux pathway, which is the pathway where cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver. As one of the key functions of HDL, their hypothesis was that if they could measure HDL-C-efflux capacity, they would have a better handle on the role of HDL in atherosclerosis. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between HDL-C functionality and MetS. The aim of this study is to examine this association of HDL-C functionality with MetS in different ages and sex., Methods and Analysis: The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar). Studies that examined the association between HDL-C functionality and MetS; focused on cohort, case-control, and cross-sectional studies; were conducted among in adults aged 40 to 70 years; provided sufficient data for calculating odds ratio or relative risk with a 95% confidence interval; were published as original articles written in English or other languages; and have been published until January 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators., Ethics and Dissemination: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal., Trial Registration Number: PROSPERO (CRD42018083465).

Background: Atherosclerosis is now widely recognized as a multifactorial disease with outcomes that arise from complex factors such as plaque components, blood flow, and inflammation. Epicardial adipose tissue (EAT) is a metabolically active fat depot, abundant in proinflammatory cytokines, and has been correlated with the extent and severity of carotid artery disease (CD). The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery (ie, the origin) and the common carotid artery bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between EAT and CD. The aim of this study is to examine this association of EAT with CD in different ages and sex., Methods: This systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that (1) examined the association between EAT and CD, (2) focus on cohort, case-control and cross-sectional studies, (3) will conducted among in adults aged 40 to 70 years, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) will published as original articles written in English or other languages, and (6) have been published until January 2018 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators., Results: We propose the current protocol to evaluate the evaluation of EAT with ED., Conclusion: This systematic review will not need ethical approval, because it does not involve human beings. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal., Ethics and Dissemination: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal., Trial Registration Number: PROSPERO (CRD42018083458).

Background: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia, and an increased risk of cardiovascular events. However, there are no systematic analyses, or well-conducted meta-analyses to evaluate the relationship between epicardial adipose tissue (EAT) and (MetS). The aim of this study is to examine this association of EAT with MetS in different ages and sex., Methods: The update systematic review, and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that firstly, examined the association between EAT and MetS, secondly, focus on cohort, case-control, and cross-sectional studies, thirdly, were conducted among in adults aged between 40 and 70 years, fourth, provided sufficient data for calculating ORs or relative risk with a 95% CI, fifth, were published as original articles written in English or other languages, and sixth, have been published until January year 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators., Results: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. This study will provide a high quality synthesis on the association of EAT and MetS., Conclusion: This systematic review will provide evidence to assess whether there is a strong association of EAT and MetS, and its components.

Background: Patients with HIV have been found to suffer from lipid abnormalities, including elevated levels of total and LDL-cholesterol as well as triglyceride levels. Abnormal lipid levels are associated with an increased risk of developing cardiovascular diseases, which are significant causes of mortality among the general population. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of statins classes on HIV patients., Methods: Randomized clinical trials (RCTs) and observational studies published in English up to 31 December 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will all-cause mortality, new event of acute myocardial infarction, stroke (hemorrhagic and ischemic), hospitalization for acute coronary syndrome and urgent revascularization procedures and cardiovascular mortality. Secondary outcomes will be assessment of the differences in change of total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (ApoB), high density lipoprotein (HDL-C). Risk of bias will be assessed using the Cochrane Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting of Observational Studies in Epidemiology instrument for observational studies. Network meta-analysis will be performed using multivariate random-effects meta-regression models. The surface under the cumulative ranking curve will be used to provide a hierarchy of statins that reduce cardiovascular mortality in HIV patients. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed., Results and Conclusion: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. The evidence will determine which combination of interventions are most promising for current practice and further investigation., Trial Registration Number: PROSPERO (CRD42017072996).

Introduction: The metabolic syndrome is composed of several cardiovascular risk factors and has a high prevalence throughout the world. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between metabolic syndrome and stroke. The aim of this study is to examine this association of metabolic syndrome with stroke in different ages and sex., Methods and Analysis: The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar. Studies that examined the association between metabolic syndrome and stroke, had a longitudinal or prospective cohort design, were conducted among in adults aged 40 to 70 years, provided sufficient data for calculating ORs or relative risk with a 95% CI, were published as original articles written in English or other languages, and have been published until December 2017 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators., Ethics and Dissemination: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. The findings from this study could be useful for assessing metabolic syndrome risk factors in stroke, and determining approaches for prevention of stroke in the future.