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Background: Working memory (WM) limitations have been suggested as a significant source of the linguistic processing deficits observed in individuals with aphasia (IWA). Digits forward (DF) and digits backward (DB) span tasks are frequently used to study WM in both healthy and clinical populations. Unfortunately only a handful of studies have explored digit span in IWA. Aims: The purpose of the current study is to measure the DF and DB spans of IWA and compare their digit spans to a group with right brain damage, but no aphasia (RBD). Additionally, DF and DB span is compared within each group to determine if there is indeed a performance differential that may support the idea that DB is a more difficult WM task in these populations. Methods & Procedures: A total of 17 IWA and 14 individuals with RBD participated in a DF and DB span task. Modifications to the span tasks were implemented to accommodate language deficits. A series of two digits were orally presented to each participant continuing to a maximum of eight digits. There were seven trials per digit series. Participants were asked to point to the correct order of digits on a written one- to nine-digit list provided on individual note cards or to verbally repeat the numbers if the participant was able to do so. Outcomes & Results: IWA demonstrated shorter digit spans than the RBD group. Both groups performed worse on the DB span tasks than the DF span tasks. Conclusions: The results are consistent with previous studies suggesting that DB span is shorter than DF span in other populations and that there are differences in performance on digit span tasks between the two groups. The differences between RBD group and IWA may be explained by decreased attentional capacity or inefficient resource allocation in IWA, or alternatively, a deficient phonological loop. Future studies should explore these possibilities. [ABSTRACT FROM AUTHOR]

Background: Motor dysfunction in the contralateral hand has been well characterised after stroke. The ipsilateral hand has received less attention, yet may provide valuable insights into the structure of the motor system and the nature of the recovery process. By tracking motor function of both hands beginning in the acute stroke period in patients with cortical versus subcortical lesions, we sought to understand the functional anatomy of the ipsilateral deficit.Methods: We examined 30 patients with first-ever unilateral hemiparetic stroke, 23 with subcortical lesions affecting the corticospinal tract, seven with cortical involvement. Patients performed hand dynamometry and the 9-Hole Peg Test (9HPT) with each hand at 24-48 h, 1 week, 3 months and 1 year after stroke. Linear regression was used to compare the two different motor tasks in each hand. Repeated measures ANOVA was used to compare recovery rates of the two tasks in the first 3 months.Results: Ipsilateral 9HPT scores averaged z = -7.1, -3.6, -2.5 and -2.3 at the four time points whereas grip strength was unaffected. The initial degree of impairment of grip strength in the contralateral hand did not correlate with the degree of impairment of 9HPT in either the contralateral or ipsilateral hand (r = 0.001, p = 0.98), whereas the initial degree of impairment of 9HPT in the contralateral hand correlated with the degree of impairment of 9HPT in the ipsilateral hand (r = 0.79, p = 0.035). The rate of recovery also differed for the two tasks (p = 0.005).Conclusion: Ipsilateral motor deficits are demonstrable immediately after stroke and extend into the subacute and chronic recovery period. Dissociation between grip strength and dexterity support the notion that dexterity and grip strength operate as anatomically and functionally distinct entities. Our findings in patients with subcortical lesions suggest that the model of white matter tract injury needs to be refined to reflect the influence of a subcortical lesion on bi-hemispheral cortical networks, rather than as a simple "severed cable" model of disruption of corticofugal fibres. Our data have implications for both stroke clinical trials and the development of new strategies for therapeutic intervention in stroke recovery. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is associated with autonomic dysregulation during pregnancy; however, less is known about autonomic function in the first week postpartum after preeclampsia., Methods: We retrospectively analyzed data from a prospective cohort of women with and without preeclampsia. Continuous blood pressure and heart rate were measured with finger plethysmography within 7 days postpartum. Frequency-domain blood pressure and heart rate variability (HRV) were calculated using spectral analysis. Time-domain HRV was calculated as the root mean square of successive RR interval differences. We compared results between those with and without preeclampsia, as well as between those with new-onset preeclampsia, chronic hypertension with superimposed preeclampsia, and normotensive participants., Results: A total of 70 postpartum women were enrolled: 20 normotensive, 29 new-onset preeclampsia, and 21 superimposed preeclampsia. Both low- and high-frequency blood pressure variabilities were higher in those with preeclampsia compared with controls ( P =0.04 and P =0.02, respectively). This difference was driven by those with new-onset preeclampsia. The preeclampsia group had lower high-frequency HRV ( P <0.005), a higher low-/high-frequency ratio of HRV ( P <0.005), and lower time-domain HRV ( P =0.01); this difference was seen in those with and without chronic hypertension., Conclusions: Postpartum patients with preeclampsia with and without chronic hypertension had lower HRV compared with normotensive postpartum controls. Higher blood pressure variability was observed only in those with nonsuperimposed preeclampsia, suggesting that the autonomic profile of preeclampsia may differ in patients with chronic hypertension.

Objectives: Race-ethnic disparities contribute to cardiovascular morbidity. Heart failure (HF) is highly prevalent in acute ischemic stroke (AIS) and associated with worse outcomes. We hypothesized race-ethnic differences exist in the prevalence of HF among patients with AIS, particularly in younger patients, and in a manner not fully explained by cardiovascular profiles., Methods: Patients with AIS in the National Inpatient Sample (2016-2019) were categorized as young (<50 years), middle (50-64) and older (≥65) age. Interaction between age and race-ethnicity on the presence of comorbid HF was examined, adjusting for vascular risk factors. Effect modification on in-hospital mortality and prolonged hospitalization across race-ethnic groups and age was also examined., Results: Of 398,470 AIS patients, 16.2 % had HF. HF patients were older (73.7 vs. 69.5 years, P < 0.001), had a lower proportion of White, Hispanic and Asian/PI individuals but a larger proportion of patients of Black race (21.0 vs. 16.4 %, P < 0.001). Race-ethnicity modified the relationship between HF and age (P interaction < 0.001). Stroke patients of Black race had the greatest odds of having HF across all age groups, however differences between Black and White patients were most pronounced in young adults (OR: 2.08, 95 % CI: 1.91-2.27) after adjusting for vascular risk factors. Among patients with HF, Black race was associated with reduced risk of in-hospital mortality but greater likelihood of prolonged hospitalization at middle and older age., Conclusion: HF is highly prevalent in stroke patients of Black race, particularly in younger cohorts, and in a manner not fully explained by cardiovascular profiles., 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 Inc. All rights reserved.)

Racial-ethnic disparities exist in the prevalence and outcomes of heart failure (HF) and are presumed to be related to differences in cardiovascular risk factor burden and control. There is little data on stroke disparities among patients with HF or the factors responsible. We hypothesized disparities in stroke prevalence exist among patients with HF in a manner not fully explained by burden of cardiovascular disease. We analyzed data from the National Health and Nutrition Examination Survey (1999-2014). Cardiovascular profiles were compared by race/ethnicity. Using survey-weighted models, effect modification of the relationship between HF and stroke by race/ethnicity was examined adjusting for cardiovascular profiles. Of 40,437 participants, 2.5 % had HF. The HF cohort had a greater proportion of White and Black participants (77 % vs 74 % and 15 % vs 12 %, respectively) and fewer participants of Hispanic ethnicity (8 % vs 14 %). Stroke was 8 times more prevalent in HF (19.6 % vs 2.3 %, <0.001). Among individuals with HF, race-ethnic differences were identified in the prevalence and mean values of vascular risk factors but were largely driven by higher rates in Black participants. There was significant interaction between HF and race/ethnicity; HF increased the odds of stroke over 7-fold in participants of Hispanic ethnicity (aOR: 7.84; 95 % CI: 4.11-15.0) but to a lesser extent in Black and White participants (Black aOR: 2.49; 95 % CI: 1.72-3.60; White aOR: 3.36; 95 % CI: 2.57-4.40). People of Hispanic ethnicity with HF have a disproportionately higher risk of stroke in a manner not fully explained by differences in vascular risk profiles., 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. Published by Elsevier Ltd.)

A previous study discovered that two speakers with moderate apraxia of speech increased their sequential motion rates after unilateral forced-nostril breathing (UFNB) practiced as an adjunct to speech-language therapy in an AB repeated-measures design. The current study sought to: (1) delineate possible UFNB plus practice effects from practice effects alone in motor speech skills; (2) examine the relationships between UFNB integrity, participant-reported stress levels, and motor speech performance; and (3) sample a participant-led UFNB training schedule to contribute to the literature's growing understanding of UFNB dosage. A single-subject (n-of-1 trial), ABAB reversal design was used across four motor speech behaviors. A 60-year-old female with chronic, severe apraxia of speech participated. The researchers developed a breathing app to assess UFNB practice integrity and administer the Simple Aphasia Stress Scale after each UFNB session. The participant improved from overall severe to moderate apraxia of speech on the Apraxia Battery for Adults. Visual inspection of graphs confirmed robust motor speech practice effects for all variables. Articulatory-kinematic variables demonstrated sensitivity to the UFNB-plus-practice condition and correlated to stress scale scores but not UFNB integrity scores. The participant achieved 20-minute UFNB sessions 4 times per week. Removal of UFNB during A2 (UFNB withdrawal) and after a 10-day break during B2 (UFNB full dosage) revealed UFNB practice effects on stress scale scores. UFNB with motor speech practice may benefit articulatory-kinematic skills compared to motor speech practice alone. Regular, cumulative UFNB practice appeared to lower self-perceived stress levels. These findings, along with prior work, provide a foundation to further explore yoga breathing and its use with speakers who have apraxia of speech.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation., Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy., Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium., Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508)., Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage., Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52])., Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Background and Objectives: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts., Methods: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates., Results: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ 2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient β = 0.020; SE = 0.009; p = 0.03)., Discussion: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.

Aims: Aortic valve stenosis (AS) results in higher systolic pressure to overcome resistance from the stenotic valve, leading to heart failure and decline in cardiac output. There has been no assessment of cerebral blood flow (CBF) association with neurocognition in AS or the effects of valve replacement. The goal was to determine if AS is associated with altered cerebral haemodynamics and impaired neurocognition, and whether transcatheter aortic valve replacement (TAVR) improves haemodynamics and cognition., Methods and Results: In 42 patients with planned TAVR, transcranial Doppler (TCD) assessed bilateral middle cerebral artery (MCA) mean flow velocities (MFVs); abnormality was <34.45 cm/s. The neurocognitive battery assessed memory, language, attention, visual-spatial skills, and executive function, yielding a composite Z -score. Impairment was <1.5 SDs below the normative mean. The mean age was 78 years, 59% Male, and the mean valve gradient was 46.87 mm/Hg. Mean follow-up was 36 days post-TAVR (range 27-55). Pre-TAVR, the mean MFV was 42.36 cm/s (SD = 10.17), and the mean cognitive Z -score was -0.22 SDs (range -1.99 to 1.08) below the normative mean. Among the 34 patients who returned after TAVR, the MFV was 41.59 cm/s (SD = 10.42), not different from baseline ( P = 0.66, 2.28-3.67). Post-TAVR, average Z-scores were 0.17 SDs above the normative mean, not meeting the pre-specified threshold for a clinically significant 0.5 SD change., Conclusion: Among patients with severe AS, there was little impairment of MFV on TCD and no correlation with cognition. Transcatheter aortic valve replacement did not affect MFV or cognition. Assumptions about diminished CBF and improvement after TAVR were not supported., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Changes in dynamic cerebral autoregulation (DCA) may contribute to postpartum maternal cerebrovascular complications after preeclampsia. We hypothesized that DCA is impaired in the first week postpartum after diagnosis of preeclampsia with severe features (PSF), compared with normotensive postpartum individuals and healthy non-pregnant female volunteers., Methods: We measured DCA within seven days after delivery in individuals with and without PSF, using transcranial Doppler and continuous arterial blood pressure monitoring with finger plethysmography. Historical data from 28 healthy female non-pregnant volunteers, collected using the same methods, were used for comparison. We used generalized harmonic wavelets to estimate autoregulation parameters (phase shift and gain) in very low frequency and low frequency bands, with lower phase shift and higher gain indicating impaired DCA function. We compared DCA parameters between the three groups using the Kruskal Wallis test., Results: A total of 69 postpartum participants contributed data, of whom 49 had preeclampsia with severe features. Median phase shifts in both postpartum groups were higher compared with historical controls across all frequency ranges (p = 0.001), indicating faster autoregulatory response. Gain was higher in both postpartum groups than in historical controls across all frequency ranges (p = 0.04), indicating impaired dampening effect., Conclusion: We found that postpartum individuals, regardless of preeclampsia diagnosis, had higher phase shifts and higher gain than healthy non-pregnant/postpartum female volunteers. Our results suggest hyperdynamic DCA with impaired dampening effect in the first week postpartum, regardless of preeclampsia diagnosis., 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 © 2023 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality., Method: We leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses., Results: Cross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events., Conclusion: In these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective. A data-driven technique for parsimonious modeling and analysis of dynamic cerebral autoregulation (DCA) is developed based on the concept of diffusion maps. Specifically, first, a state-space description of DCA dynamics is considered based on arterial blood pressure, cerebral blood flow velocity, and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. We assessed the reliability of the technique by considering healthy individuals and patients with unilateral internal carotid artery (ICA) stenosis or occlusion. We computed the sensitivity of the technique to detect the presumed side-to-side difference in the DCA function of the second group (assuming hypoactive dynamics on the occluded or stenotic side), using McNemar's chi square test. The results were compared with transfer function analysis (TFA). The performance of the two methods was also compared under the assumption of missing data. Main results. Both diffusion maps and TFA suggested a physiological side-to-side difference in the DCA of ICA stenosis or occlusion patients with a sensitivity of 81% and 71%, respectively. Further, both two methods suggested the difference between the occluded or stenotic side and any two sides of the healthy group. However, the diffusion maps captured additional difference between the unoccluded side and the healthy group, that TFA did not. Furthermore, compared to TFA, diffusion maps exhibited superior performance when subject to missing data. Significance. The eigenvalues ratio derived using the diffusion maps technique can be potentially used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function., (© 2023 Institute of Physics and Engineering in Medicine.)

Background and Objectives: In response to the COVID-19 pandemic, outpatient stroke care delivery was rapidly transformed to outpatient evaluation through video (VTM) and telephone (TPH) telemedicine (TM) visits around the world. We sought to evaluate the sociodemographic differences in outpatient TM use among stroke patients., Methods: We conducted a retrospective chart review of outpatients evaluated at 3 tertiary stroke centers in the early period of the pandemic, 3/16/2020 through 7/31/2020. We compared the use of TM by patient characteristics including age, sex, race/ethnicity, insurance status, stroke type, patient type, and site. The association between TM use and patient characteristics was measured using the relative risk (RR) from a modified Poisson regression, and site-specific effects were controlled using a multilevel analysis., Results: A total of 2,024 visits were included from UTHealth (n = 878), MedStar Health (n = 269), and Columbia (n = 877). The median age was 64 [IQR 52-74] years, and 53% were female. Approximately half of the patients had private insurance, 36% had Medicare, and 15% had Medicaid. Two-thirds of the visits were established patients. TM accounted for 90% of total visits, and the use of TM over office visits was primarily associated with site, not patient characteristics. TM utilization was associated with Asian and other/unknown race. Among TM users, older age, Black race, Hispanic ethnicity, and Medicaid insurance were associated with lower VTM use. Black (aRR 0.88, 95% CI 0.86-0.91, p < 0.001) and Hispanic patients (aRR 0.92, 95% CI 0.87-0.98, p = 0.005) had approximately 10% lower VTM use, while Asian patients (aRR 0.98, 95% CI 0.89-1.07, p = 0.59) had similar VTM use compared with White patients. Patients with Medicaid were less likely to use VTM compared with those with private insurance (aRR 0.86, 95% CI 0.81-0.91, p < 0.001)., Discussion: In our diverse cohort across 3 centers, we found differences in TM visit type by race and insurance early during the COVID-19 pandemic. These findings suggest disparities in VTM access across different stroke populations. As VTM remains an integral part of outpatient neurology practice, steps to ensure equitable access are essential., Competing Interests: I.A. Naqvi is currently supported by National Center for Advancing Translational Sciences, NIH, through Grant No. KL2TR001874 and American Heart Association Grant No. 923718. M.C.Denny is a member of the Abbott speakers bureau and receives grant funding support from National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) and MedStar Health Research Institute; however, none of these are related to this work. A.Z. Sharrief is a consultant for Abbott and receives grant funding from the National Institute of Minority Health and Health Disparities (NIMHD). The other authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.TAKE-HOME POINTS→During the early period of the pandemic, telemedicine use accounted for 90% of all outpatient stroke clinic visits.→Inequities were noted among Black and Hispanic patients and those with Medicaid insurance with lower video telemedicine use.→Time to implementation, site practices in types of visits offered, and barriers in transition to telehealth during the pandemic contributed to differences in utilization among sites., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

WSS measurement is challenging since it requires sensitive flow measurements at a distance close to the wall. The aim of this study is to develop an ultrasound imaging technique which combines vector flow imaging with an unsupervised data clustering approach that automatically detects the region close to the wall with optimally linear flow profile, to provide direct and robust WSS estimation. The proposed technique was evaluated in phantoms, mimicking normal and atherosclerotic vessels, and spatially registered Fluid Structure Interaction (FSI) simulations. A relative error of 6.7% and 19.8% was obtained for peak systolic (WSS PS ) and end diastolic (WSS ED ) WSS in the straight phantom, while in the stenotic phantom, a good similarity was found between measured and simulated WSS distribution, with a correlation coefficient, R, of 0.89 and 0.85 for WSS PS and WSS ED , respectively. Moreover, the feasibility of the technique to detect pre-clinical atherosclerosis was tested in an atherosclerotic swine model. Six swines were fed atherogenic diet, while their left carotid artery was ligated in order to disturb flow patterns. Ligated arterial segments that were exposed to low WSS PS and WSS characterized by high frequency oscillations at baseline, developed either moderately or highly stenotic plaques (p < 0.05). Finally, feasibility of the technique was demonstrated in normal and atherosclerotic human subjects. Atherosclerotic carotid arteries with low stenosis had lower WSS PS as compared to control subjects (p < 0.01), while in one subject with high stenosis, elevated WSS was found on an arterial segment, which coincided with plaque rupture site, as determined through histological examination.

Background and Purpose: High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere., Methods: We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis., Results: Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032)., Conclusions: Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

A large portion of stroke disparities remains unexplained, even after adjusting for demographic, comorbidity, and health care access variables. There is a critical need to close this knowledge gap by investigating novel factors that may contribute to stroke disparities. Allostatic load (AL) is the lifetime adverse physiologic impact of needing to adjust to socially structured stressors such as racism. AL has been shown to increase health vulnerability and worsen outcomes in marginalized populations. We sought to assess the differential impact of AL on cognitive outcomes post intracerebral hemorrhage (ICH) across race-ethnicity. The Intracerebral Hemorrhage Outcomes Project (ICHOP) prospectively collected data from patients presenting to Columbia Medical Center with ICH from 3/2009 to 5/2016. Data included demographics, stroke scores, labs, complications, neuroimaging, medical history, and discharge data. Five markers of AL (HbA1c, WBC, SBP, HR, ALB) were obtained. An AL score was generated by summing the elements in each patient that fell outside normal ranges, with AL score ranging 0-5. A linear regression model, adjusted for stroke severity and ICH volumes, was used to evaluate the relationship between AL and Modified Telephone Interview for Cognitive Status (TICS-m) at discharge, stratified by race-ethnicity. Among 248 white, 195 black, and 261 Hispanic ICH patients, neither mean AL nor mean TICS differed by race/ethnicity (p = 0.51, p = 0.79 respectively). In the overall cohort AL did not predict TICS at discharge (Beta -1.0, SE 1.1, p = 0.353). In Whites (beta 1.18, SE 2.5, p = 0.646) and Hispanics (beta -0.95, SE 1.6, p = 0.552) AL was not associated with TICS at discharge. In Black patients, higher AL was associated with a decrease in TICS at discharge (beta -3.2, SE 1.5, p = 0.049). AL is an important determinant of post ICH outcomes for certain minority populations. AL may explain some of the unexplained health disparities in stroke populations., (© 2022. The Author(s).)

A prototype main-ion CHarge Exchange Recombination Spectroscopy (mCHERS) diagnostic is providing measurements of the main-ion (hydrogen or deuterium) temperature and velocity in the C-2W field reversed configuration plasma using charge exchange Balmer-alpha emission at five different radial locations with 500 Hz frequency and a per-pixel velocity resolution of 15 km/s. Measurement along the entire plasma radius of C-2W is enabled by a diagnostic neutral beam (DNB) that passes through the center of plasma, unlike the larger diameter heating neutral beams that have impact parameters of 20 cm. DNB provides high time resolution via beam modulation and spatial resolution via its small cross section. The goals of the current mCHERS upgrade are to double the number of spatial channels, improve the per-pixel velocity resolution by three times, and increase the measurement frequency to match the maximum modulation frequency of the diagnostic neutral beam (∼10 kHz). To accomplish these goals, a new astigmatism-free Isoplane spectrometer has been commissioned. Progress and results from the newly upgraded mCHERS system are detailed.

Background: Hypertension is the most important modifiable risk factor for recurrent stroke, and blood pressure (BP) reduction is associated with decreased risk of stroke recurrence. However, hypertension remains poorly controlled in many stroke survivors. Black and Hispanic patients have a higher prevalence of uncontrolled BP and higher rates of stroke. Limited access to care contributes to challenges in post-stroke care. Telehealth After Stroke Care (TASC) is a telehealth intervention that integrates remote BP monitoring (RBPM) including nursing telephone support, tailored BP infographics and telehealth video visits with a multidisciplinary team approach including pharmacy to improve post-stroke care and reduce stroke disparities., Methods: In this pilot trial, 50 acute stroke patients with hypertension will be screened for inclusion prior to hospital discharge and randomized to usual care or TASC. Usual care patients will be seen by a primary care nurse practitioner at 1-2 weeks and a stroke neurologist at 1 and 3 months. In addition to these usual care visits, TASC intervention patients will see a pharmacist at 4 and 8 weeks and will be enrolled in RBPM consisting of home BP monitoring with interval calls by a centralized team of telehealth nurses. As part of RBPM, TASC patients will be provided with a home BP monitoring device and electronic tablet that wirelessly transmits home BP data to the electronic health record. They will also receive tailored BP infographics that help explain their BP readings. The primary outcome will be feasibility including recruitment, adherence to at least one video visit and retention rates. The clinical outcome for consideration in a subsequent trial will be within-patient change in BP from baseline to 3 months after discharge. Secondary outcomes will be medication adherence self-efficacy and satisfaction with post-stroke telehealth, both measured at 3 months. Additional patient reported outcomes will include depression, cognitive function, and socioeconomic determinants. Multidisciplinary team competency and fidelity measures will also be assessed., Conclusions: Integrated team-based interventions may improve BP control and reduce racial/ethnic disparities in post-stroke care. TASC is a post-acute stroke care model that is novel in providing RBPM with tailored infographics, and a multidisciplinary team approach including pharmacy. Our pilot will determine if such an approach is feasible and effective in enhancing post-stroke BP control and promoting self-efficacy., Trial Registration: ClinicalTrials.gov NCT04640519., (© 2022. The Author(s).)

As central effectors of ubiquitin (Ub)-mediated proteolysis, proteasomes are regulated at multiple levels, including degradation of unwanted or dysfunctional particles via autophagy (termed proteaphagy). In yeast, inactive proteasomes are exported from the nucleus, sequestered into cytoplasmic aggresomes via the Hsp42 chaperone, extensively ubiquitylated, and then tethered to the expanding phagophore by the autophagy receptor Cue5. Here, we demonstrate the need for ubiquitylation driven by the trio of Ub ligases (E3s), San1, Rsp5, and Hul5, which together with their corresponding E2s work sequentially to promote nuclear export and Cue5 recognition. Whereas San1 functions prior to nuclear export, Rsp5 and Hul5 likely decorate aggresome-localized proteasomes in concert. Ultimately, topologically complex Ub chain(s) containing both K48 and K63 Ub-Ub linkages are assembled, mainly on the regulatory particle, to generate autophagy-competent substrates. Because San1, Rsp5, Hul5, Hsp42, and Cue5 also participate in general proteostasis, proteaphagy likely engages a fundamental mechanism for eliminating inactive/misfolded proteins., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort., Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles., Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P <0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile ( P =0.015). Lower performance was attributed largely to Word List Recall ( P <0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, P ≤0.01). The scores for left versus right carotid disease were similar., Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.

A main ion charge exchange recombination spectroscopy (mChERS) diagnostic has been developed to measure the velocity and temperature of the main deuterium ions in the C-2W (also called Norman) field-reversed configuration (FRC) device. A modulated diagnostic neutral beam (DNB) of hydrogen with 40 keV full energy and a nominal current of 8.5 A provides the charge exchange signal. The DNB can achieve a fast modulation frequency of up to 10 kHz, a rare attribute to find on other fusion devices, which defines the time resolution of mChERS. Currently, the mChERS diagnostic provides simultaneous measurements at five spatial locations in the FRC plasma using a high-speed camera. The design and capabilities of the mChERS system are presented along with first experimental data.

Introduction: Cardiovascular and cerebrovascular diseases (CCVDs) are the leading cause of maternal mortality in the first year after delivery. Women whose pregnancies were complicated by pre-eclampsia are at particularly high risk for adverse events. In addition, women with a history of pre-eclampsia have higher risk of CCVD later in life. The physiological mechanisms that contribute to increased CCVD risk in these women are not well understood, and the optimal clinical pathways for postpartum CCVD risk reduction are not yet defined., Methods and Analysis: The Motherhealth Study (MHS) is a prospective cohort study at Columbia University Irving Medical Center (CUIMC), a quaternary care academic medical centre serving a multiethnic population in New York City. MHS began recruitment on 28 September 2018 and will enrol 60 women diagnosed with pre-eclampsia with severe features in the antepartum or postpartum period, and 40 normotensive pregnant women as a comparison cohort. Clinical data, biospecimens and measures of vascular function will be collected from all participants at the time of enrolment. Women in the pre-eclampsia group will complete an additional three postpartum study visits over 12-24 months. Visits will include additional detailed cardiovascular and cerebrovascular phenotyping. As this is an exploratory, observational pilot study, only descriptive statistics are planned. Data will be used to inform power calculations for future planned interventional studies., Ethics and Dissemination: The CUIMC Institutional Review Board approved this study prior to initiation of recruitment. All participants signed informed consent prior to enrolment. Results will be disseminated to the clinical and research community, along with the public, on completion of analyses. Data will be shared on reasonable request., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patients with stroke-like symptoms may be underutilising emergency medical services and avoiding hospitalisation during the COVID-19 pandemic. We investigated a decline in admissions for stroke and transient ischaemic attack (TIA) and emergency department (ED) stroke alert activations., Methods: We retrospectively compiled total weekly hospital admissions for stroke and TIA between 31 December 2018 and 21 April 2019 versus 30 December 2019 and 19 April 2020 at five US tertiary academic comprehensive stroke centres in cities with early COVID-19 outbreaks in Boston, New York City, Providence and Seattle. We collected available data on ED stroke alerts, stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and time from symptom onset to hospital arrival., Results: Compared with 31 December 2018 to 21 April 2019, a decline in stroke/TIA admissions and ED stroke alerts occurred during 30 December 2019 to 19 April 2020 ( p trend <0.001 for each). The declines coincided with state stay-at-home recommendations in late March. The greatest decline in hospital admissions was observed between 23 March and 19 April 2020, with a 31% decline compared with the corresponding weeks in 2019. Three of the five centres with 2019 and 2020 stroke alert data had a 46% decline in ED stroke alerts in late March and April 2020, compared with 2019. Median baseline NIHSS during these 4 weeks was 10 in 2020 and 7 in 2019. There was no difference in time from symptom onset to hospital arrival., Conclusion: At these five large academic US hospitals, admissions for stroke and TIA declined during the COVID-19 pandemic. There was a trend for fewer ED stroke alerts at three of the five centres with available 2019 and 2020 data. Acute stroke therapies are time-sensitive, so decreased healthcare access or utilisation may lead to more disabling or fatal strokes, or more severe non-neurological complications related to stroke. Our findings underscore the indirect effects of this pandemic. Public health officials, hospital systems and healthcare providers must continue to encourage patients with stroke to seek acute care during this crisis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Phosphatidylinositol 3-phosphate (PI3P) is an essential membrane signature for both autophagy and endosomal sorting that is synthesized in plants by the class III phosphatidylinositol 3-kinase (PI3K) complex, consisting of the VPS34 kinase, together with ATG6, VPS15, and either VPS38 or ATG14 as the fourth subunit. Although Arabidopsis ( Arabidopsis thaliana ) plants missing the three core subunits are infertile, vps38 mutants are viable but have aberrant leaf, root, and seed development, Suc sensing, and endosomal trafficking, suggesting that VPS38 and ATG14 are nonredundant. Here, we evaluated the role of ATG14 through a collection of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and T-DNA insertion mutants disrupting the two Arabidopsis paralogs. atg14a atg14b double mutants were relatively normal phenotypically but displayed pronounced autophagy defects, including reduced accumulation of autophagic bodies and cargo delivery during nutrient stress. Unexpectedly, homozygous atg14a atg14b vps38 triple mutants were viable but showed severely compromised rosette development and reduced fecundity, pollen germination, and autophagy, consistent with a need for both ATG14 and VPS38 to fully actuate PI3P biology. However, the triple mutants still accumulated PI3P, but they were hypersensitive to the PI3K inhibitor wortmannin, indicating that the ATG14/VPS38 component is not essential for PI3P synthesis. Collectively, the ATG14/VPS38 mutant collection now permits the study of plants altered in specific aspects of PI3P biology., (© 2020 American Society of Plant Biologists. All rights reserved.)

The core protease (CP) subcomplex of the 26S proteasome houses the proteolytic active sites and assumes a barrel shape comprised of four co-axially stacked heptameric rings formed by structurally related α- and β-subunits. CP biogenesis typically begins with the assembly of the α-ring, which then provides a template for β-subunit integration. In eukaryotes, α-ring assembly is partially mediated by two hetero-dimeric chaperones, termed Pba1-Pba2 (Add66) and Pba3-Pba4 (also known as Irc25-Poc4) in yeast. Pba1-Pba2 initially promotes orderly recruitment of the α-subunits through interactions between their C-terminal HbYX or HbF motifs and pockets at the α 5 -α 6 and α 6 -α 7 interfaces. Here, we identified PBAC5 as a fifth α-ring assembly chaperone in Arabidopsis that directly binds the Pba1 homolog PBAC1 to form a trimeric PBAC5-PBAC1-PBAC2 complex. PBAC5 harbors a HbYX motif that docks with a pocket between the α 4 and α 5 subunits during α-ring construction. Arabidopsis lacking PBAC5, PBAC1 and/or PBAC2 are hypersensitive to proteotoxic, salt and osmotic stresses, and display proteasome assembly defects. Remarkably, whereas PBAC5 is evolutionarily conserved among plants, sequence relatives are also dispersed within other kingdoms, including a scattered array of fungal, metazoan and oomycete species., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Autophagic recycling of proteins, lipids, nucleic acids, carbohydrates, and organelles is essential for cellular homeostasis and optimal health, especially under nutrient-limiting conditions. To better understand how this turnover affects plant growth, development, and survival upon nutrient stress, we applied an integrated multiomics approach to study maize ( Zea mays ) autophagy mutants subjected to fixed-carbon starvation induced by darkness. Broad metabolic alterations were evident in leaves missing the core autophagy component ATG12 under normal growth conditions (e.g., lipids and secondary metabolism), while changes in amino acid-, carbohydrate-, and nucleotide-related metabolites selectively emerged during fixed-carbon starvation. Through combined proteomic and transcriptomic analyses, we identified numerous autophagy-responsive proteins, which revealed processes underpinning the various metabolic changes seen during carbon stress as well as potential autophagic cargo. Strikingly, a strong upregulation of various catabolic processes was observed in the absence of autophagy, including increases in simple carbohydrate levels with a commensurate drop in starch levels, elevated free amino acid levels with a corresponding reduction in intact protein levels, and a strong increase in the abundance of several nitrogen-rich nucleotide catabolites. Altogether, this analysis showed that fixed-carbon starvation in the absence of autophagy adjusts the choice of respiratory substrates, promotes the transition of peroxisomes to glyoxysomes, and enhances the retention of assimilated nitrogen., (© 2020 American Society of Plant Biologists. All rights reserved.)