bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 265: CITED4 Induces Physiologic Hypertrophy and Improves Cardiac Remodeling After Ischemic Injury
Authors: Bezzerides Vassilios J , Platt Colin , Paruchuri Kaavya , Oh Loren , Xiao Chunyang , Mann Nina , Rosenzweig Anthony 
Published: July 2021

Cardiac hypertrophy is an adaptive response to increased hemodynamic stresses, which can be either physiologic, as with exercise, or pathologic, as with valvular heart disease. Recent data suggest that physiologic hypertrophy secondary to exercise may be mediated by the transcription factor CEBPβ and the p300-interacting protein CITED4. We sought to investigate the cardiovascular effects of CITED4 expression in vivo.
Using a cardiac-specific and inducible transgenic mouse (Tg) model, we determined the effects of CITED4 expression on cardiac parameters including heart weight, cell size, cardiac function and gene expression. Expression of CITED4 for 3 weeks induced increases in heart weight (22% in HW/TL, p < 0.01) and cardiomyocyte (CM) size (24.5% in cell area, p < 0.001) with normal systolic function and without evidence of fibrosis. Gene profiling demonstrated increased expression of cardiac troponin, a favorable αMHC/βMHC ratio and a reduction in BNP consistent with physiologic hypertrophy. Genome-wide expression profiling of neonatal rat ventricular myocytes (NRVMs) over-expressing CITED4 demonstrated the activation of a unique set of genes including BCL2, ATP12a, Efemp1, Ifi204 and Tcf19.
To further examine the potential beneficial role of CITED4, we induced ischemia by transient occlusion of the left anterior descending (LAD) coronary (30 min) followed by reperfusion for 24 hours, 6 days or 4 weeks. At 24 hrs after ischemia-reperfusion injury (IRI), neither cardiac dysfunction on echo nor infarct sizes were different between CITED4 Tg and controls. However, CITED4 Tgs showed substantial recovery of cardiac function at 4 weeks (FS: CITED4 Tg 51%, Control 34%, p < 0.01) and a 3.4-fold reduction in fibrosis (p < 0.005). Analysis of possible cellular responses responsible for the functional recovery demonstrated enhanced autophagic flux with reduced accumulation of LC3II (down 71%, p<0.05) and p62 (down 54%, p<0.005). Further examination of the involved signaling pathway revealed direct activation of mTORC1 and its effectors consistent with a growth phenotype.
We conclude that CITED4 expression is sufficient to induce physiologic cardiac hypertrophy and improves cardiac remodeling after ischemic injury likely through activation of mTORC1.
Antihypertensive Effect of Clonidine
Authors: ONESTI GADDO , SCHWARTZ ALLAN B. , KIM KWAN E. , PAZ-MARTINEZ VIRGILIO , SWARTZ CHARLES 
Published: July 2021

Clonidine hydrochloride is a sympathetic inhibitor with central site of action. The antihypertensive effect in man in the supine position is associated with a decrease in cardiac output and no consistent changes in total peripheral resistance. In the standing position, however, in addition to the decrease in cardiac output, a fall in total peripheral resistance becomes evident. The fall in blood pressure results in no significant alteration in renal blood flow or glomerular filtration rate in the supine position. In the standing position a consistent decrease in renal vascular resistance is seen.
In the anesthetized dog the intravenous administration of clonidine produces a significant reduction of renal vein plasma renin activity. Similarly, in patients with essential hypertension oral administration of the drug results in a decrease in peripheral plasma renin activity.
In ambulatory essential hypertensive patients treated with clonidine alone in doses of 400 to 900 µg per day, a modest antihypertensive effect is achieved. When clonidine is used with a diuretic, antihypertensive efficacy is achieved in 80% of the patients treated. In higher doses (up to 3,600 µg per day) and in combination with a diuretic, the antihypertensive effect appears to be superior to that of many of the standard agents. Drowsiness and dryness of the mouth are the most frequent and serious side effects with the higher doses.
Abstract 216: Minimally Invasive Surgery plus Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) Leads to a Reduction in Perihematomal Edema
Authors: Mould W. Andrew , Carhuapoma J. Ricardo , Muschelli John , Hanley Daniel F ,   and the MISTIE Investigators
Published: July 2021

Background:
Intracerebral hemorrhage (ICH) remains the most devastating form of stroke without treatment. Secondary damage such as perihematomal edema (PHE) can negatively impact long-term outcome. Several reports suggest that blood and its degradation products lead to PHE. Treatments aimed at blood removal and edema prevention have a potential to improve outcome in these stroke patients. We hypothesized that successful hematoma evacuation would reduce PHE volume.

Methods:
MISTIE is a multi-center, prospective, randomized trial testing the safety and efficacy of hematoma evacuation after spontaneous ICH compared to medical management. Study interventions were consistently applied in a protocol-based manner across study sites. We conducted a semi-automated, computerized volumetric analysis on CT imaging to assess the effect of hematoma removal on PHE. Both arms of the study were assessed for ICH and PHE volumes at two time points: T1, pre-enrollment, and T2, end of treatment.

Results:
Of 123 patients enrolled, 79 surgical and 39 medical patients were analyzed. There was no significant difference between the treatment cohorts in age, enrollment GCS, intraventricular involvement, baseline ICH volume, or baseline PHE volume. Mean hematoma volume at T2 was 19.64±14.5 cc for the surgical cohort and 40.74±13.9 cc for the medical cohort (p&lt0.001). Mean edema volume at T2 was 27.67±13.3 cc for the surgical cohort while medical patients had 41.69±14.6 cc (p&lt0.001). When patients within each treatment arm were subdivided into groups of &gt65%, 20-65%, and &lt20% ICH removal, surgical patients were 32, 39, and 8 respectively, whereas all medical patients experienced &lt20% clot removal. A significant difference in edema volume was seen among the three groups (ANOVA p&lt0.001). On further analysis, there was a positive correlation between edema reduction and percent of ICH removed: the more ICH removed, the greater the reduction in edema (Spearman R=0.645; p&lt0.001).

Conclusion:
Safe, early, and effective hematoma evacuation of parenchymal blood in ICH is associated with significant reduction in perihematomal edema, especially when a high percentage of blood is removed.
Abstract TP196: New Zealand Workforce Stroke Incidence: Urban and Rural Risk Factor Evaluation
Authors: Buell Hope E , Metcalf Patricia , Exeter Daniel 
Published: July 2021

This analysis aims to assess the impact of urban and rural risk factors on a model of stroke incidence in a New Zealand workforce population.
The New Zealand study consisted of 4,926 subjects prospectively enrolled at 46 worksites. The subjects were aged 40-78 years at baseline and had no prior history of stroke. This prospective study defines stroke events experienced by the study subjects during follow-up between 1988 and 2012 based on hospital admission coding. Proportional hazards regression models were fit using baseline characteristics. The difference in stroke outcomes for urban and rural worksites was also evaluated.
Results demonstrate that baseline demographic, physical exam, and behavioural measures impact stroke outcomes. While the baseline distribution of stroke risk factors such as Pacific Island ethnicity, smoking status, and increased blood pressure indicates a potentially higher risk of stroke in the rural population, the proportional hazards model does not identify increased stroke risk for rural workers. Additional analysis of the diet, exercise and Quality of Life measures for these subjects may provide further information into the stroke risk profiles of individuals working in different locales.
Abstract TP200: Independent Contribution of HbA1c, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Ischemic Stroke Hospitalizations in Type 2 Diabetes
Authors: Nichols Gregory A , Parasuraman Shreekant , Joshua-Gotlib Sandra 
Published: July 2021

Risk of ischemic stroke is approximately doubled in patients with diabetes. To reduce risk, managing diabetes includes optimizing glycemic, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) control. We studied which risk factors alone or in combination were most strongly associated with stroke hospitalizations.
We identified 26,924 Kaiser Permanente Northwest members with type 2 diabetes and no known prior cardiovascular disease hospitalization. Beginning in 2002, we identified the earliest point patients had glycosolated hemoglobin (HbA1c), systolic BP (SBP), and LDL-C measurements within 6 months of each other and followed them until they died, disenrolled, or 31 December 2011. Outcome was hospitalization with primary diagnosis of ischemic stroke. Using mean HbA1c, SBP, and LDL-C between baseline and end of follow-up, we identified dichotomous categories of control of HbA1c (<7%), SBP (<130 mm Hg) and LDL-C (<100 mg/dL) and estimated the relative risk of stroke hospitalization independently associated with all combinations of risk factors controlling for age, sex, diabetes duration, comorbidities, body mass index, smoking, and pharmacotherapy.
Mean (SD) age of patients was 59 (12) years; 50% were men. Over mean (SD) follow-up of 6.2 (2.8) years, 606 (2.3%) patients were hospitalized for ischemic stroke. Compared with patients with all 3 risk factors in control, patients who had no risk factors controlled or only HbA1c controlled had >2-fold increased risk of ischemic stroke. Patients who controlled both SBP and LDL-C had significantly lower risk relative to control of all 3 risk factors.

In this observational study, maintaining control of SBP over 6.2 years was essential to reduction of ischemic stroke risk. Simultaneous control of LDL-C further reduced risk, but HbA1c control <7% did not mitigate stroke risk beyond SBP and LDL-C control. Further research is needed to evaluate the relationship between HbA1c control and stroke risk.
Abstract TP92: Brain Activity Related To The Effects Of Augmented Feedback On Learning Movements In A Dynamic Environment In Healthy Subjects And Stroke Survivors
Authors: Mukherjee Mukul , Chang Wen-Pin , Siu Ka-Chun , Fayad Pierre , Stergiou Nicholas 
Published: July 2021

Augmented visual feedback has been shown to be effective for learning reaching movements in dynamic environments after a stroke. However, the mechanisms behind such changes are not known. In addition, how brain activity changes with age as we learn novel dynamic tasks is also not clear. The purpose of this study was to examine brain activity changes that are observed when healthy younger and older adults and stroke survivors learn reaching movements in dynamic environments using augmented visual feedback.
Healthy young and older adults and chronic stroke survivors were randomly assigned to either a control or an experimental group. They all performed reaching movements with the Inmotion2 robotic system (Interactive Motion Tech Inc., MA) using the dominant/affected arm in a velocity-dependent force field. Controls received actual feedback of their movement, while experimental subjects received augmented visual feedback. Electroencephalogram recordings were analyzed to determine Event Related Desynchronization percent (ERD%). The theta, alpha, and beta frequency bands were examined during movement and pre-movement phases.
With learning, the absolute power of the frequency bands increased from the baseline to the adaptation condition, which was then washed out when the force field was removed. With age, there was a reduction in ERD% in alpha and beta bands as the motor task was learned. Stroke subjects had a further reduction in the ERD% in comparison to the healthy older adults. In addition, augmented visual feedback led to a significant increase in the ERD% in comparison to controls during the planning and execution stages of the movement.
Past studies have shown when novel dynamics are learned, ERD% reduces indicating increased cognitive processing and memory load. We found that with aging, the cognitive processing and memory required for performing the same dynamic task, increased. After a stroke, there was a further increase. However, the utilization of augmented visual feedback may reduce such requirements and lessen the load on higher centers. These results provide mechanistic support for employing augmented visual feedback for stroke rehabilitation specific to reaching movements in dynamic environments.
Abstract WP328: A Nurse-Led Initiative Improves Adherence Rates for Stroke Follow-up and Blood Pressure Management
Authors: Larsen Darren T , Lutsep Helmi L 
Published: July 2021

Background and Issues
Aggressive management of vascular risk factors reduces stroke rates. It is unknown whether structured nurse-led follow up increases adherence rates for stroke patients after hospital discharge.

Purpose
The purpose of this program is to improve secondary stroke risk factor management by instituting a nurse-led initiative called Stroke Therapy, Education, Prevention (STEP).

Methods
The pilot STEP program was based on protocols used for other stroke prevention trials. This nurse-led program includes inpatient initiation and outpatient maintenance of pharmacologic and lifestyle goals for stroke patients.

Eligible patients have a non-disabling ischemic stroke or TIA and are without insurance restrictions and live within a distance allowing return to clinic for follow up.
Prior to discharge, the STEP nurse completes patient education, and reviews outpatient goals.
The STEP nurse makes phone contact with the patient 7-10 days after discharge to review medication compliance and reinforce education.
At 30 days post discharge patients are seen in clinic by the STEP nurse where a resting blood pressure (BP) is measured. If the patient does not meet targets (<140 SBP or <130 SBP for DM) medications are adjusted by a stroke neurologist.
We undertook a retrospective chart review of a consecutive cohort of patients matched to STEP eligibility criteria to determine whether the program improved retention rates and BP management. Chi-Square analysis was used to compare visit adherence and percentage achieving goal BPs at 30 days.

Results
In the STEP group 25/32(78%) patients completed the 30 day follow up compared to 14/32 (44%) patients in the historical matched cohort (p=0.0048). Target BP was achieved in 13/25(52%) STEP patients and 5/14 (36%) matched cohort patients (p=0.32) returning to clinic. Overall, target BP was achieved in 13/32 (41%) and 5/32 (16%) respectively (p=0.026).

Conclusions
In conclusion, follow up adherence and BP management in the group as a whole was better in the nurse-led model and is recommended for secondary stroke prevention. Long term follow up with this model may further increase in-target rates of BP control and other stroke risk factors.
Abstract 80: Early Intervention With High-Dose Statin Decreased the Plaque in Acute Stroke Patients With Intracranial Atherosclerosis: High-Resolution MR Wall Imaging Study
Authors: Ryoo Sookyung , Kim Suk Jae , Cha Jihoon , Moon Gyeong Joon , Kim Gyeong-Moon , Chung Chin-Sang , Lee Kwang Ho , Bang Oh Young 
Published: July 2021

Intracranial atherosclerosis (ICAS) is a common stroke etiology, especially in Asians. Current guidelines emphasize statin therapy with intensive lipid lowering effects for risk reduction in atherosclerotic strokes. High-dose statin therapy regress coronary, carotid and aortic atherosclerotic plaques. However the role of statin in patients with ICAS remains unknown. Thus we aimed to evaluate the impact of early intervention with rosuvastatin (20mg/day) on the symptomatic intracranial atherosclerotic plaque, using high-resolution (HR) wall MRI.
Fiffteen patients with acute infarcts caused by ICAS were enrolled. All patients were given high-dose statin, rosuvastatin 20mg/day and performed serial HR MRI with 3-T scanner including proton density/T2-weighted axial/sagittal, T1 FLAIR pre- and post-contrast sagittal/axial and 3-dimensional volumetric isotropic turbo spin echo acquisition images. Serial HR wall MRI were taken before and after 3~6 months of treatment (interval, 141±45 days). Intracranial artery at the maximal stenosis on MRA was analyzed in terms of vascular remodeling (plaque burden) and wall enhancement (plaque activation). Normal vessels were also assessed for reference values. Intracranial atherosclerotic plaques were compared before and after statin treatment.
Both intracranial atherosclerotic plaque burden and activation can be regressed by high-dose statin therapy (Figure). Wall area, a representative of plaque burden, was decreased (pre- vs. post-statin treatment, 5.74±2.63mm2 vs. 4.64±2.58mm2; p=0.027). Enhanced area within the wall, an indicator of plaque activation, was also lowered (pre- vs. post-statin treatment, 3.46±2.15mm2 vs. 2.32±1.81mm2; p=0.013). No patients stop rosuvastatin during follow-up period.
Early intervention with high-dose rosuvastatin in acute stroke patients with ICAS enabled significant reduction of the symptomatic intracranial atherosclerotic plaque during 6 months.
Abstract T P225: cGMP-Dependent Protein Kinase I in Smooth Muscle Cells Protects Against Stroke Injury in Mice
Authors: Atochin Dmitriy , Buys Emmanuel , Swanson Helen , Dordea Ana , Fukumura Dai , Feil Robert , Huang Paul L 
Published: July 2021

The signaling pathways by which NO protects against stroke injury are mediated by cyclic guanosine monophosphate (cGMP) formation. However, the mechanisms of downstream signaling from cGMP to smooth muscle cells (SMC) remain incompletely understood. The cGMP-dependent protein kinase I (cGKI) is a key mediator of cGMP signaling.
The goal of this study is to test the hypothesis that cGKI in SMC protects against stroke injury.

Animals:
We used the novel mouse line for highly efficient tamoxifen-inducible SMC-specific gene knockout, SMA-CreERT2, which expresses the CreERT2 recombinase under the control of the smooth muscle alpha-actin promoter (cGKI KO mice). The litter mate wild-type (WT) mice (no Cre gene) receiving the same tamoxifen treatment were used as control (cGKI WT) mice.

Methods and Results:
Mean blood pressure measured acutely from the common carotid artery under anesthesia (30% oxygen, 70% nitrous oxide and 1.5% isoflurane) was higher in cGKI KO mice (107±8 mmHg, Mean±SD) than in cGKI WT mice (95±1 mmHg, n=4/group, P<0.05). One hour of middle cerebral artery (MCA) occlusion by filament with 23 hours of reperfusion produced increased cerebral infarct volume (TTC staining, indirect calculation) in cGKI KO mice (123±39 mm3) as compared with cGKI WT (85±17 mm3, n=5/group, p< 0.05). Neurological deficit by 5 point scale was worse in cGKI KO mice (4.0 points) as compared with cGKI WT (2.4 points). Cerebral blood flow monitored by laser Doppler flowmetry above the core of the MCA territory indicated that reperfusion was less in cGKI KO mice than in cGKI WT mice, suggesting that cGKI mediates cerebrovascular SMC relaxation and protects against ischemic stroke. Vascular relaxation of mesenteric resistance arteries to acetylcholine, and the NO donor, NONOate after preconstriction with phenylephrine was dramatically impaired in cGKI KO mice. It suggests the importance of cGKI in the vascular SMC for NO-induced relaxation.

In conclusion, stroke injury was more pronounced in cGKI SMC specific inducible conditional knockout mice than in cGKI WT mice, suggesting a protective role for cGKI in SMC against cerebral reperfusion injury. These studies identify the cGKI in cerebral vasculature as a potential target for therapies aimed at reducing stroke injury.
Abstract W P192: A Direct Telecommunication Between Doctors of a Comprehensive Stroke Center and Local Hospitals Significantly Shortened the Door-to-Puncture Time for Intraarterial Thrombectomy
Authors: Jeong Hye Seon , Kwon Hyunjo , Koh Hyunsong , Yu Heesun , Yun Nayoung , Oh Sang-Geun , Kwag Hyun Jeong , Song Hee-Jung , Kim Jei 
Published: July 2021

Background:
We evaluated whether a direct doctor-to-doctor telecommunication (D2D-Call) between a comprehensive stroke center and local hospitals was effective to rapidly start intraarterial thrombectomy (IAT) for acute ischemic stroke patients, who first visit local hospital.

Methods:
Clinical data of 92 consecutive patients (male:female, 63:29; mean age±standard deviation, 68.6±11.4 years), who underwent IAT for terminal internal carotid and/or middle cerebral artery occlusions, were analyzed. The patients were classified by arrival manners at Stroke Center; 1) Direct-Arrival at Center (n=59), 2) Arrival after D2D-Call (n=20), and 3) Arrival without D2D-call (Non-D2D-Call, n=13). The D2D-call system had three parts; 1) D2D-Call for transfer, 2) activation of IAT team before arrival, and 3) immediate start of IAT after arrival of a patient. Time intervals from arrival to IAT start (Arrival-to-IAT) and from symptom onset to recanalization (Onset-to-Recanalization) was compared between three groups. The rates of recanalization and good clinical outcome (0-3 of the modified Rankin Scale) of three groups were also compared.

Results:
The Arrival-to-IAT time was significantly shorter in D2D-Call than other two groups (Direct-Arrival, 103.3±21.6; D2D-Call, 41.3±15.1; Non-D2D-Call group, 107.5±19.0 minutes, p<0.001).

The Onset-to-Recanalization time was also shortened in D2D-call (Direct-Arrival, 286.4±89.5; D2D-Call, 324.5±61.2; Non-D2D-Call group, 402.5±67.1 minutes, p=0.001).
Even though recanalization rate (Direct-arrival, 88%; D2D-call-transfer, 75%; Non-D2D-call-transfer group, 77%, p=0.302) was similar between three groups, D2D-Call patients showed similar good clinical outcomes like as Direct-Arrival patients at 3 months after IAT (Direct-Arrival, 64%, D2D-call, 60%; Non-D2D-call group, 39%, p=0.080).

Conclusion:
The direct telecommunication between doctors of a Stroke Center and local hospitals could significantly shorten the start time for IAT and achieved better clinical outcomes for transferred ischemic stroke patients.