bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P128: Prevalence of Posttraumatic Stress Disorder Due to Stroke: A Meta-analysis
Authors: Edmondson Donald , Richardson Safiya , Fausett Jennifer K , Falzon Louise , Howard Virginia J , Kronish Ian M 
Published: July 2021

Title:
Prevalence of posttraumatic stress disorder due to stroke: A meta-analysis

Objective:
To estimate the prevalence of stroke-induced posttraumatic stress disorder (PTSD) using systematic review and meta-analysis.

Methods:
Potentially relevant peer-reviewed journal articles were identified by searching the Ovid MEDLINE, PsycINFO, PILOTS Database, The Cochrane Library and Scopus from inception to April 2012; all searches were conducted on April 13, 2012. Observational cohort studies that assessed PTSD with specific reference to a stroke or TIA that occurred at least 1 month prior to the PTSD assessment were included. We abstracted PTSD rates and characteristics of the study and sample from all included studies. The coding of all articles included demographic information, sample size, study country, and method and timing of PTSD assessment.

Results:
Eight studies (N= 1,111) met our inclusion criteria. PTSD prevalence estimates varied significantly across studies by timing of PTSD assessment (ie., within 1 year of stroke vs greater than 1 year post-stroke; 70% of heterogeneity explained;
Q
1
=14.68;
P
<.001). The final aggregate prevalence estimate was 14% (95% CI, 11%-17%) from the random effects model comprised of an aggregate estimate of 25% (95% CI, 17%-35%) for PTSD within 1 year of stroke and 11% (95% CI, 8%-14%) after 1 year.

Conclusions:
Although posttraumatic stress disorder (PTSD) is commonly thought to be triggered by external events such as combat or sexual assault, these results suggest that as many as 1 in 4 stroke survivors develop significant PTSD symptoms due to the stroke. Further research is needed to determine whether stroke-induced PTSD increase recurrence risk in stroke patients.

Figure 1. Stroke-induced PTSD prevalence estimates
Note: The area of each square is proportional to the study’s weight in the meta-analysis, and each line represents the confidence interval around the estimate. Diamonds represent aggregate estimates, by PTSD assessment timing and overall.
Abstract P167: The Long-term Effect of a Low-Carbohydrate Diet on Appetite Hormones: A Randomized Controlled Trial
Authors: Hu Tian , Reynolds Kristi , Yao Lu , Bunol Calynn , Liu Yanxi , Chen Chung-Shiuan , He Jiang , Bazzano Lydia 
Published: July 2021

The long-term effects of low-carbohydrate diets on hormones related to appetite are unclear.
We recruited a total of 148 study participants with a body mass index of 30 - 45 kg/m2 (Mean: 35.4 kg/m2) who were free of diabetes, cardiovascular diseases and kidney disease. The participants were randomly assigned to either a low-carbohydrate diet (<40 g/day; N=75) or a low fat (<30% energy from fat, <10% from saturated fat; N=73) diet. Two 24-hour dietary recalls were conducted at each clinic visit (0, 3, 6 and 12 months of the intervention). Participants met with a study dietitian weekly for the first month followed by group settings bi-weekly for 5 months then monthly for the subsequent 6 months. Each group was provided the same behavioral curriculum related to diet emphasizing portion control and eating habits. Total ghrelin and peptide YY were determined using radioimmunoassay methods.
Of the study participants, 60 in the low-fat group (81.1%) and 59 in the low-carbohydrate group (79.7%) completed the entire intervention. The mean age was 46.8 years, 88.5% were women and 55.1% were African-Americans. The low-carbohydrate group lost approximately 3.5 kg more body weight than did the low-fat group (P value: 0.002) over the course of the intervention. Both diets decreased total peptide YY and ghrelin. Compared to low-fat diets, the low-carbohydrate diet resulted in a significantly greater decrease in total peptide YY at 6 (Net change: -6.8 ph/mL; P value: 0.04) and 12 months (Net change: -10.6 ph/mL; P value: 0.02). The changes in total ghrelin were not significantly different throughout the study.
Our findings suggest that the low-carbohydrate diet did not result in a greater loss of appetite, compared to the low-fat diet.
Abstract P425: Associations between Physical Activity, Cardiorespiratory Fitness, Abdominal Obesity and Cardiometabolic Risk in Obese Women
Authors: Clarke John , Shalev-Goldman Einat , McGuire Ashlee , Ross Robert 
Published: July 2021

The independent associations between abdominal obesity, cardiorespiratory fitness (CRF), physical activity (PA) and cardiometabolic risk factors in obese women is unclear. We studied 165 sedentary, abdominally obese women (waist circumference 106.4 ± 10.2 cm, age 51.0 ± 7.8y). Objective measures of PA volume and intensity were obtained by accelerometry and CRF by a maximal treadmill test. Plasma glucose and serum insulin were obtained during a 2-hour glucose tolerance test. The homeostasis model of assessment (HOMA-IR) was used to estimate insulin resistance. Fasting levels for triglycerides, total cholesterol, and high-density lipoproteins were also obtained. Systolic and diastolic blood pressure was measured using the BP True method.
With few exceptions PA variables alone were not associated with any cardiometabolic risk factors. WC was associated with all cardiometabolic risk factors except DBP, 1 and 2-hour glucose (p≤0.05). CRF alone was associated with SBP, fasting insulin, and HOMA-IR (p≤0.05). Multivariate analysis revealed associations between WC and HOMA-IR (r2=0.24, p<0.001), fasting insulin (r2=0.25, p<0.001), fasting glucose (r2=0.03, p<0.05), TG (r2=0.05, p<0.05), and HDL (r2=0.06, p<0.05) following adjustment for PA, and CRF. CRF, PA intensity and PA volume were not associated with cardiometabolic risk factors following control for each other and WC.
In this study of sedentary, abdominally obese women objective measures of PA intensity and volume were not associated with cardiometabolic risk factors independent of WC and CRF. WC was associated with most of the cardiometabolic risk factors independent of PA and CRF; however, the associations with measures of insulin metabolism were modest whereas the associations with lipid variables and blood pressure were weak.
Abstract P439: Risk Factor Profile and Prevalence of Subclinical Disease in African Americans with Diabetes and Metabolic Syndrome: The Jackson Heart Study
Authors: Gharaibeh Kamel A , Xanthakis Vanessa , Sung Jung Hye , Samdarshi Tandaw S , Taylor Herman A , Sims Mario , Vasan Ramachandran S , Fox Ervin R 
Published: July 2021

Background
. Metabolic derangements such as diabetes (DM) and metabolic syndrome (MetS) are common in African Americans (AA) and contribute to the higher cardiovascular disease (CVD) mortality in this group. A greater prevalence of subclinical disease (ScD) among those with DM and MetS in the AA community may be an explanatory factor.

Objective
. We assessed the CVD risk factor profile and distribution of ScD among AA with DM and MetS in the Jackson Heart Study (JHS).

Methods
. We evaluated 4,365 AA participants [mean age (SD) of 53.8 (12.3) years, 64.5% women] free of overt CVD who attended JHS Exam 1 (between 2000- 2004), when ScD assessment was routinely performed(with the exception of CT for coronary calcium that occurred in Exam2). SCD measures included 1) peripheral artery disease (PAD, defined as ankle-brachial index<0.9), 2) high coronary artery calcium (CAC, defined as score>100), 3) left ventricular (LV) hypertrophy (LVH defined as left ventricular mass index>51 g/m
2.7
, 4) low LV ejection fraction (low EF, defined as an EF<50%), and 5) microalbuminuria (MA, defined as an albumin-to-creatinine ratio>25 μg/mg in men and >35 μg/mg in women). We compared the distribution of standard CVD risk factors and ScD prevalence in 1) those without DM or MetS (referent), 2) those with MetS but no DM and 3) those with DM.

Results
. In our study sample, 1,089 (24.9%) had MetS with no DM and 752 (17.2%) had DM. Compared to the referent group, groups with metabolic derangement tended to be older, female, hypertensive, obese, and had lower HDL, higher fasting glucose, and higher triglycerides levels. Table 1 compares the distribution of ScD for the three groups, and demonstrates the greater odds of. CAC, LVH and microalbuminuria in participants with MetS or DM.

Conclusion
. In our large community-based sample of AAs, we observed a significantly high prevalence of ScD overall, especially so in participants with MetS and DM. These findings likely contribute to the high CVD rates in AA with MetS and DM.
Abstract 11685: Early Myocardial Gene Expression Profiling After Deep Hypothermic Circulatory Arrest Reveals Ontogenetic Adaptive Mechanisms Underlying Ischemia-Reperfusion Tolerance in the Swine
Authors: Yamada Miki , Sheikh Amir , Collins Kevin , Frederiksen James , Quick George , Lodge Andrew , Podgoreanu Mihai 
Published: July 2021

Previous studies suggest that immature hearts are more tolerant to ischemia than adult myocardium; whether differences exist during ontogenic development in severity of global myocardial ischemia/reperfusion (I/R) injury associated with cardiac surgery remains unknown. We employed swine models of deep hypothermic circulatory arrest (DHCA) to test the hypothesis that early differential regulation of cardioprotective genes is associated with increased tolerance of neonatal myocardium to surgical I/R.
Male neonatal and adult pigs were randomized to DHCA or sham (N=5-14/group). DHCA animals underwent cardiopulmonary bypass (18°C), DHCA 60 min, and were recovered for 3h. Severity of perioperative myocardial injury was determined biochemically (Troponin I) and echocardiographically. Transcript levels were quantified in left ventricular myocardium using Affymetrix Porcine Genome arrays, followed by differential expression and pathway analysis.
A 2-fold increase in severity of perioperative myocardial injury was found in adult pigs (Fig.A). Of 596 transcripts differentially expressed in neonates (≥1.5-fold change, DHCA vs. sham, FDR<0.05), 53 were shared with adults (Fig.B). Among them, divergent expression patterns were found for oxysterol binding protein-like 6 (down-regulated in adults up-regulated in neonates) and bromodomain adjacent to zinc finger domain 2B (up-regulated in adults - down-regulated in neonates). Top transcripts uniquely upregulated in neonates but unchanged in adults were the apoptosis inhibitor baculoviral IAP repeat containing 2, and signal transducer and activator of transcription 3. mTOR signaling and p53 signaling were the top canonical pathways deregulated in adults and neonates, respectively.
A high resistance to surgical I/R injury in neonatal vs adult swine heart is correlated with robust differences in early transcriptional programs, suggesting the involvement of fundamental adaptive ontogenetic processes.
Abstract 11936: Development of Monthly to Quarterly Subcutaneous Administration of RNAi Therapeutics Targeting the Metabolic Diseases Genes PCSK9, ApoC3 and ANGPTL3
Authors: Borodovsky Anna , Querbes William , Sutherland Jessica , Hutabarat Renta , Milstein Stuart , Kuchimanchi Satya , Kuchimanchi Rajeev , Charisse Klaus , Yucius Kristina , Liebow Abigail , Sprague Andrew , Maier Martin , Kallend David , Simon Amy , Horton Jay , Fitzgerald Kevin 
Published: July 2021

Introduction:
Cardiovascular disease remains the top cause of mortality in the United States. We have developed, and validated in human trials, a platform for reducing the synthesis of genes expressed in the liver. The platform utilizes a GalNAc sugar ligand attached to the 3’end of the sense strand of an RNAi molecule to enable delivery specifically to the liver. Here we present data from this platform on multiple targets of interest in cardiovascular disease, including PCSK9, ANGPLT3 and ApoC3.

Hypothesis:
RNAi therapeutics targeting liver genes of interest (such as PCSK9, ApoC3 and Angptl3) will allow for control of lipid levels and reduce the risk of cardiovascular disease.

Methods:
Chemically modified siRNAs were designed using bioinformatic algorithms and were screened for potency
in vitro
. pM active siRNA molecules were developed targeting PCSK9, ANGPLT3 and ApoC3.

Results:
ALN-PCSsc: In NHPs a single dose of ALN-PCSsc at ≥ 6 mg/kg reduced circulating PCSK9 levels up to 97% and LDL-C up to 67%. Moreover the nadir effect ( where LDL-C is clamped) lasted ~90 days suggesting that once monthly to quarterly dosing could be supported. Multidose studies in NHP at 2 mg/kg reduced circulating PCSK9 levels up to 94% with a subsequent lowering of LDL-C up to 67%. Safety studies in rat and NHP at doses up to 300 mg/kg (multi-dose) showed that ALN-PCSsc was safe demonstrating potential for a very wide therapeutic index. ALN-PCSsc was selected as a development candidate and is being advanced towards an IND for the treatment of hypercholesterolemia.

ALN-ANGsc: Was tested in two models of hyperlipidemia, the OB/OB mouse and the hCETP-ApoB mouse. In the Ob/Ob model, treatment with ALN-ANGsc at 3mg/kg resulted in a significant lowering ANGPLT3 protein (>95%), cholesterol (>60%) and triglycerides (>85%).
ALN-ApoC3: Was tested in the db/db mouse model of hyperlipidemia. A robust lowering of plasma ApoC3 (>90%) lead to a >50% lowering of triglycerides. Screening for both programs is underway for a development candidates.

Conclusions:
We have developed a modular, robust and reliable platform for the delivery of RNAi therapeutics to the liver with a large therapeutic index. This small volume, subcutaneous, platform has a remarkable duration of effect.
Abstract 11964: Circulating Levels of 2-Aminobutyric Acid Reflect Myocardial Redox State in Patients With Atrial Septal Defects
Authors: Irino Yasuhiro , Toh Ryuji , Mori Takeshige , Nagao Manabu , Honjo Tomoyuki , Satomi-Kobayashi Seimi , Shinke Toshiro , Ishida Tatsuro , Miyata Okiko , Hirata Ken-ichi 
Published: July 2021

Heart failure (HF) is a major cause of morbidity and mortality worldwide. However, conventional biomarkers are insufficient to detect early stage of HF and identification of more sensitive markers is an urgent task. We conducted the comprehensive quantification of water-soluble metabolites in blood of atrial septal defect (ASD) patients using a gas chromatograph-mass spectrometry. We found the mean level of 2-Aminobutyric acid (2-AB) in ASD patients was significantly higher than that in healthy volunteers, and 1 month after transcatherter closure of ASD using the Amplatzer septal occluder, serum 2-AB levels in patients decreased to almost the same levels as healthy volunteers (healthy-volunteers: 15.74±1.75 μM, ASD (pre-closure): 22.38±1.99 μM, ASD (post-closure):15.50±1.50 μM, P=0.017). In contrast, serum levels of brain natriuretic peptide (BNP), frequently used as the biomarker in heart disease, did not show such relationships. In addition, 2-AB concentration had a significant correlation with tricuspid regurgitation peak gradient (TRPG) (R2=0.517, P=0.029). Because TRPG reflects right ventricular loading conditions, we examined whether mechanical stress to cardiomyocyte induces 2-AB. Mechanical stretch induced an accumulation of 2-AB, suggesting that circulating 2-AB increased in ASD patients were derived from their hearts.
Next, we tried to identify the 2-AB synthesis pathway. 2-AB is known as a key molecule in the biosynthesis of ophthalmic acid that is an analogue of glutathione (GSH) and indicates GSH depletion under oxidative stress. We revealed that 2-AB was produced as the byproduct of GSH synthesis reactions. We also demonstrated that oxidative stress lead to 2-AB production by H2O2 stimulation in cardiomyocyte. Mechanical stress-induced 2-AB accumulation might be mediated by oxidative stress.
In summary, circulating 2-AB levels changed before and after closure of ASD and indicated heart condition more efficiently than BNP. We also demonstrated that 2-AB reflects myocardial redox state. Thus, 2-AB monitoring may facilitate the early diagnosis strategy for HF.
Abstract 11968: Nocturnal Blood Pressure in Young Adults and Cognitive Function in Midlife: The CARDIA Study
Authors: Yano Yuichiro , Ning Hongyan , Muntner Paul , Reis Jared , Calhoun David , Viera Anthony , Levine Deborah , David Jacobs , Shimbo Daichi , Liu Kiang , Greenland Philip , Lloyd-Jones Donald 
Published: July 2021

Nocturnal blood pressure (BP) is associated with risk for cardiovascular events. However, the effect of nocturnal BP in young adults on cognitive function in midlife remains unclear.
We used data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, including 224 participants (mean age 30 years, 45% men, 63% African Americans) followed for 20 years (6 visits). At the 20-year follow-up, the Stroop test (higher score indicates worse executive function), Digit Symbol Substitution Test (DSST, lower score indicates worse psychomotor speed), and Rey Auditory Verbal Learning Test (RAVLT, lower score indicates worse verbal memory) were assessed.
Baseline mean office, daytime, and nocturnal BP were 109/73mmHg, 120/74mmHg, and 107/59mmHg, respectively. Nocturnal BP dipping, calculated as (nocturnal systolic BP [SBP]-daytime SBP)х100/daytime SBP, was divided into quartiles (Q1;-39.3% to -16.9%, Q2;-16.8% to -13.2%, Q3 [reference];-13.1% to -7.8%, and Q4;-7.7% to +56.4%).
Cognitive function score according to the quartile of nocturnal SBP dipping is shown in Figure. In linear regression models, the least nocturnal SBP dipping (Q4 vs. reference) and higher nocturnal diastolic BP (DBP) level were associated with worse Stroop scores, with adjustments for demographic and clinical characteristics, and cumulative exposure of BP during follow-up (β [standard error]: 0.37[0.18] and 0.19[0.07] respectively; all P<0.05). Neither DSST nor RALVT was associated with either nocturnal BP dipping or nocturnal SBP/DBP levels.
Among healthy young adults, less nocturnal SBP dipping and higher nocturnal DBP levels were associated with lower executive function in midlife, independent of long-term office BP levels. Nocturnal BP measures in young adults could be potentially useful to identify those who may be at risk for developing lower cognitive function in midlife.
Abstract 12279: Novel and Reliable Method to Screen for Drug Cardiac Toxicity Using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (hiPS-CM)
Authors: Mohamed Tamer M , Ellinger Bernhard , Stankovikj Vera , Wiesinger Adriana , Guan Kaomei , Neyses Ludwig , Oceandy Delvac , Gul Sheraz , Cartwright Elizabeth J 
Published: July 2021

Unexpected cardiotoxicity underlies high rates of attrition during drug development, posing a multi-billion dollar burden on the pharmaceutical industry. Over reliance on the use of animals and materials derived from animals in preclinical assays to predict the cardiotoxic effect of new drugs in humans has contributed to this problem. The drug responses in human cardiomyocytes compared to animal-derived primary cardiomyocytes (CM) for
in vitro
assays is not always the same. Here, we describe a combination of human pluripotent stem cell-derived cardiomyocytes (hiPS-CM) and high content analysis confocal microscopy as a potential solution for this major setback in drug development.

Initially human skin fibroblasts were reprogrammed into human induced pluripotent stem cells (hiPSCs) by lentiviral transduction and utilization of the following combination of transcription factors: Oct3/4, Sox2, c-Myc and Klf4. The human pluripotent stem cell phenotype of the generated hIPSCs was confirmed. hiPSCs were differentiated into cardiomyocytes and the cardiac cell phenotype was confirmed by immunofluorescence and RT-PCR analysis of cardiac markers i.e. αMHC, cTNT, NKX2.5 and connexin 43. Seventeen known cardiotoxic compounds, as well as controls, were applied to the cells in 384 well format at a dose of 10μM for 48 hours. Then hiPSC-CM underwent confocal microscopy high content analysis to simultaneously evaluate the cell mitochondrial transmembrane potential (using TMRM dye), and plasma membrane permeability (using TOTO-3 dye). All known cardiotoxins showed a significant decrease in mitochondrial transmembrane potential ranging from 74% to 95% and an increase in plasma membrane permeability ranging from 67-327 fold in comparison to the controls. These results showed 100% prediction rate of cardiotoxicity of known cardiotoxins by hiPS-CM. This was compared to only 12% general cytotoxicity prediction rate when these compounds tested on A549 and ACHN cancer cell lines.
In conclusion, combining two state of the art technologies 1) hiPSC-CM and 2) confocal microscopy high content analysis, we were able to provide a reliable high throughput method to assess cardiotoxicity of compounds.
Abstract 12412: Imaging the PM/AICD Patient; Does the Diagnostic Value Justify the Risk?
Authors: Samar Huma Y , Yamrozik June , Williams Ronald , Doyle Mark , Biederman Robert 
Published: July 2021

Background:
MR imaging is infrequently performed on patients with implanted pacemakers/AICDs. When the risk justifies the end, however, consideration to perform 'high-risk’ scanning can be made on a case-by-case basis but typically with trepidation. This raises a critically important question: "Is the MRI scan adding valuable and irrefutable information to warrant such risk?

Methods:
84 patients with implanted devices (13AICD,10 AICD/PM,5 retained leads, 6 REVO and 50 dual chamber PM.) were imaged via MRI/CMR (1.5T GE, Milwaukee, WI) over 3 years in a single institution. Specific criteria were followed for all patients to objectively define whether final diagnosis by MRI imaging enhanced patient care. A checklist of 3 questions was answered following scan interpretation by both the technologist and performing MRI physician(s):

1)
Did the diagnosis change?

2)
Did the MRI provide additional information to the existing diagnosis?

3)
Did patient management change?

If ‘Yes’ was answered to any of the above questions, it was considered that the MRI scan was of value to patient diagnosis and/or therapy.

Results:
All patients completed the procedure with no death, VT/VF, power-on-reset or adverse events. Average MRI study time: 20±55min. The device was interrogated pre and post MRI by EP/cardiologist to determine changes in impedance, amplitude or threshold. No clinically meaningful changes occurred, no post-procedure revisions to generator/lead or parameters were required.

Conclusion:
The use of PM/AICD imaging in MRI remains controversial. Our study shows that MR imaging in carefully selected patients under the supervision of experienced physicians is not only safe but extremely beneficial, substantially adding value and often irrefutable information to patient diagnosis and management. PM/AICDs when imaged properly are safe and no longer 'forbidden’ in the MRI environment. Moreover there is frequently marked life-altering and life-saving information obtained.