bluuebunny/crossref_metadata_2025 huggingface dataset:
Torque System Modeling and Electromagnetic Coupling Characteristics Analysis of a Midpoint Injection Type Bearingless Permanent Synchronous Magnet Motor
Authors: Bu Wenshao , Li Hang
Published: April 2024

Taking the Midpoint Injection type Bearingless Permanent Magnet Synchronous Motor (MPI-BL-PMSM) as an object, to solve its problems of large torque pulsation and insufficient suspension force when adopting Midpoint Suspension Current Unilateral Injection (MPSC-UI), a Midpoint Suspension Current Bilateral Injection (MPSC-BI) solution is proposed. Based on the half-winding structure of MPI-BL-PMSM, and from the electromechanical energy conversion principle, the torque model for MPSC-BI solution is established. On this basis, the torque model for MPSC-UI method was derived. The correctness of the established torque mathematical models based on half-winding structure was verified through the finite element method (FEM), and the “dual-frequency” electromagnetic coupling characteristics of suspension current on electromagnetic torque were compared and analyzed from the perspectives of theoretical model and FEM simulation. The results indicate that the MPSC-BI method can effectively suppress or avoid the torque pulsation coupled by suspension current and can obtain about 1-time increase of controllable suspension force; the advantages of MPSC-BI solution in dynamic torque decoupling characteristics are demonstrated, while the only downside is that the coupling effect of torque current on radial suspension force is slightly greater than that of the MPSC-UI method.
Obstacles of Online Learning Facing Nursing Students after the COVID-19 Pandemic
Authors: Khatatbeh Haitham , Alkhalaileh Murad , Ayasreh Ibrahim , Habahbeh Atallah , Alosoufe Laith , Alhroub Nisser , Albashtawy Mohammed , Abu-Abbas Manar , Al-Dwaikat Tariq , Mohammed Ali Amira
Published: April 2024

Background. After the COVID-19 pandemic, the online style of instruction started to replace the traditional style in Jordan. Aims. This study aims to (1) assess the nursing students’ perceived obstacles to online learning in Jordan; (2) explore significant relationships between participants’ characteristics and their perceived obstacles; and (3) assess for significant differences in the perceived obstacles based on participants’ characteristics. Methods. A cross-sectional, descriptive design was utilized in this study. A convenient sample of 325 nursing students responded to a self-reported questionnaire utilizing Google Forms. Both descriptive and inferential statistics were used to analyze the dataset using the SPSS software. Results. The mean scores of the obstacles to online learning were 2.94 (SD = 0.95) for the academic obstacles subscale, 2.90 (SD = 0.83) for the technological obstacles subscale, and 3.25 (SD = 1.00) for the administrative obstacles subscale. Significant associations were found between participants’ characteristics and perceived obstacles to online learning. For instance, the type of university was significantly associated with academic (r = −0.32, p<0.01), technological (r = −0.21, p<0.01), and administrative obstacles (r = −0.32, p<0.01). Furthermore, significant differences were found in the perceived obstacles based on the participants’ demographic and studentship-related characteristics. Conclusions. According to their perceptions of online learning, nursing students in Jordan face three types of obstacles: academic, technical, and administrative. Decision-makers should intervene to enhance the online learning experience by overcoming the reported obstacles.
Global Cognition, Gender, and Level of Education Predict Dual-Task Gait Speed Variability Metrics in Older Adults
Authors: Kline Paul W. , Shaikh Faisal D. , Tennant Jaclyn E. , Hamel Renee , Zukowski Lisa A.
Published: April 2024

Introduction: The purpose of this study was to determine if demographic variables and measures of cognitive function, functional mobility, self-reported balance self-efficacy, and self-reported physical activity can predict gait speed variability during single-task walking (STGSCV), during cognitive-motor dual-tasking (DTGSCV), and dual-task effect on gait speed variability (DTEGSCV) in older adults. Methods: In 62 older adults, demographics were recorded and cognitive function (including the Montreal Cognitive Assessment, MoCA), functional mobility, balance self-efficacy (Activities-specific Balance Confidence Scale, ABC), and self-reported physical activity (Physical Activity Scale for the Elderly, PASE) were assessed. Three linear regression models were used to determine whether the functional mobility tests, PASE score, ABC score, and tests of cognitive function predicted gait speed variability outcomes (STGSCV, DTGSCV, DTEGSCV), with demographics included as covariates. Results: MoCA score (p = 0.003), gender (p = 0.040), and years of education (p = 0.010) significantly predicted DTGSCV (R2 = 0.297, p = 0.002). MoCA score (p = 0.008) and years of education (p < 0.001) also significantly predicted DTEGSCV. Despite a significant regression model (R2 = 0.316, p = 0.001), there were no significant individual predictors of STGSCV. Conclusion: Older adults with lower cognitive function scores, according to the MoCA, and higher levels of education demonstrate larger gait speed variability during dual-tasking and may be at increased risk of real-world mobility issues or falling.
Endoscopic Resection of Malignancies in the Upper GI Tract: A Clinical Algorithm
Authors: Denzer Ulrike Walburga
Published: April 2024

Background: Malignancies in the upper gastrointestinal tract are amenable to endoscopic resection at an early stage. Achieving a curative resection is the most stringent quality criterion, but post-resection risk assessment and aftercare are also part of a comprehensive quality program. Summary: Various factors influence the achievement of curative resection. These include endoscopic assessment prior to resection using chromoendoscopy and HD technology. If resectability is possible, it is particularly important to delineate the lateral resection margins as precisely as possible before resection. Furthermore, the correct choice of resection technique depending on the lesion must be taken into account. Endoscopic submucosal dissection is the standard for esophageal squamous cell carcinoma and gastric carcinoma. In Western countries, it is becoming increasingly popular to treat Barrett’s neoplasia over 2 cm in size and/or with suspected submucosal infiltration with en bloc resection instead of piece meal resection. After resection, risk assessment based on the histopathological resection determines the patient's individual risk of lymph node metastases, particularly in the case of high-risk lesions. This is categorized according to the current literature. Key Messages: This review presents clinical algorithms for endoscopic resection of esophageal SCC, Barrett’s neoplasia, and gastric neoplasia. The algorithms include the pre-resection assessment of the lesion and the resection margins, the adequate resection technique for the respective lesion, as well as the post-resection risk assessment with an evidence-based recommendation for follow-up therapy and surveillance.
The Effect of Clothes on Blood Pressure Measurement in Normotensive and Hypertensive Subjects in a Real-Life Setting
Authors: Castillo Velarde Edwin , Roca-Sánchez-Moreno Jorge , Núñez Muñoz Alison , Guillen Rivera Alessandra , Hidalgo Babilonia Mary , García Meneses Jherson , Mamani Turpo Lisseth , Cepeda Horna Willian
Published: April 2024

Introduction: The effect of clothing on the recording of blood pressure in a normotensive and hypertensive population remains essential to diagnosing and managing. Methods: This is a cross-sectional study to measure blood pressure using a validated oscillometric sphygmomanometer in two populations. The records were made over the thicker sleeve arm and non-sleeved arm (either on bare arm or indicating the removal of the outermost garment). Clothing was categorized according to how patients attended the outpatient clinic based on the real world. Results: A total of 75 patients were included with a diagnosis of hypertension whose mean age was 67.1 years (SD ± 16.3). The group of normotension included 63 patients whose mean age was 21.1 years (SD ± 2.2). There was not variability related to technique or inherent to the condition of the subject on the first and second measurements of blood pressure. In the comparative analysis, the group with normotension did not report a significant difference in systolic or diastolic blood pressure due to the effect of clothing during the first or second measurement (p > 0.05). In the group with hypertension, a significant difference was observed in the first measurement, between the group over-the-sleeve and non-sleeved arm (systolic blood pressure, p: 0.021 and diastolic, p: 0.001). However, when the variable order of measurement was analyzed by randomizing the initial registry with or without clothing was not found a statistical difference. Conclusion: Clothing does not a significant difference in the measure of blood pressure in a normotensive or hypertensive population.
Contrasting Effects of Music Therapy and Aromatherapy on Perioperative Anxiety: A Systematic Review and Meta-Analysis
Authors: Xiang Si-Rui , Ma Qiong , Dong Jing , Ren Yi-Feng , Lin Jun-Zhi , Zheng Chuan , Xiao Ping , You Feng-Ming
Published: April 2024

Introduction: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. Methods: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). Results: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: −0.12, 0.68; p = 0.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; p = 0.02), while those at 4 h after surgery indicated the opposite results (WMD, −0.48 cm; 95% CI: −0.60, −0.36; p < 0.001). Conclusion: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicate that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.
Longitudinal Feasibility of the Montreal Cognitive Assessment (MoCA) in Non-Demented ALS Patients
Authors: Aiello Edoardo Nicolò , Solca Federica , Torre Silvia , Colombo Eleonora , Maranzano Alessio , De Lorenzo Alberto , Patisso Valerio , Treddenti Mauro , Curti Beatrice , Morelli Claudia , Doretti Alberto , Verde Federico , Ferrucci Roberta , Barbieri Sergio , Ruggiero Fabiana , Priori Alberto , Silani Vincenzo , Ticozzi Nicola , Poletti Barbara
Published: April 2024

Introduction: The present study aimed at testing the longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented amyotrophic lateral sclerosis (ALS) patients. Methods: N = 39 non-demented ALS patients were followed-up at a 5-to-10-month interval (M = 6.8; SD = 1.4) with the MoCA and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Practice effects, test-retest reliability, and predictive validity (against follow-up ECAS scores) were assessed. Reliable change indices (RCIs) were derived via a regression-based approach by accounting for retest interval and baseline confounders (i.e., demographics, disease duration, and severity and progression rate). Results: At retest, 100% and 69.2% of patients completed the ECAS and the MoCA, respectively. Patients who could not complete the MoCA showed a slightly more severe and fast-progressing disease. The MoCA was not subject to practice effects (t[32] = −0.80; p = 0.429) and was reliable at retest (intra-class correlation = 0.82). Moreover, baseline MoCA scores predicted the ECAS at retest. RCIs were successfully derived – with baseline MoCA scores being the only significant predictor of retest performances (ps < 0.001). Conclusions: As long as motor disabilities do not undermine its applicability, the MoCA appears to be longitudinally feasible at a 5-to-10-month interval in non-demented ALS patients. However, ALS-specific screeners – such as the ECAS – should be preferred whenever possible.
Current Understanding of Timing of Surgical Repair for Ventricular Septal Rupture following Acute Myocardial Infarction
Authors: Wang Shilin , Liu Hao , Yang Peiwen , Wang Zhiwen , Chen Shu
Published: April 2024

Background: Ventricular septal rupture (VSR) is a mechanical issue that can occur following an acute myocardial infarction (AMI) and has a high mortality rate. It requires a comprehensive, team-based approach for prompt diagnosis and maintaining stable blood flow. While the occurrence of VSR has lessened over the past hundred years and advancements have been made in treatment techniques, the mortality rate within 30 days can still surpass 40 percent. Surgery is the primary treatment method. For patients with stable blood flow, it is generally considered safer to perform surgery 4–6 weeks after the AMI to repair the VSR. However, the timing of surgery for patients with early instability in their blood flow is still a topic of debate. Summary: There is a lack of set criteria and standards to determine the best time for surgery in patients with VSR following an infarction who have unstable blood flow, especially when considering the use of blood circulation support devices and other techniques for maintaining blood flow that are used in clinical settings. Key Messages: This review outlines the features of different mechanical circulatory support devices utilized in treating VSR, along with the current scoring system designed to direct the treatment approach for VSR patients.
A new Ecitophilous species of Ecitoxenia Wasmann (Coleoptera, Staphylinidae) from Colombia
Authors: Campbell J. M.
Published: April 2024

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Two New Southeastern Brazilian Genera of Hypoptopomatinae and a redescription of Pseudotocinclus Nichols, 1919 (Ostariophysi, Loricariidae)
Authors: Britski Heraldo A. , Garavello Julio C.
Published: April 2024

.
Nova espécie de Paratelmatobius (Amphibia, Anura, Leptodactylidae) da Serra do Mar, Brasil
Authors: Giaretta Ariovaldo A. , Castanho Luciano M.
Published: April 2024

.
As Viagens de Johann Natterer no Brasil, 1817-1835
Authors: Vanzolini P. E.
Published: April 2024

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Abstract 187: Reduced Rapid Delayed Rectifier (I
Kr
) and Inward Rectifier Current (I
K1
) Contribute Action Potential Prolongation and Diastolic Depolarization in a Chronic Canine Heart Failure Model
Authors: Sridhar Arun , Nishijima Yoshinori , Kijtawornrat Anusak , Hamlin Robert L , Carnes Cynthia A
Published: April 2024

Heart Failure (HF) produces prolongation of the action potential duration (APD). Since human HF is a chronic syndrome, we used a chronic canine HF model to study HF-induced changes in K
+
currents and action potentials (APs). METHODS: Right ventricular tachypacing (5–24 months) was used to induce heart failure with increases in QRS Amplitude, QRS widening, Left Ventricular (LV) Mass, and LV dimensions. LV myocytes were isolated from lateral mid-myocardial wall; perforated whole cell patch clamp was done at 36°C. RESULTS: The AP duration was significantly prolonged in the HF dogs compared to controls (Panel A). Chronic HF produced a large reduction in the transient outward K
+
current (I
to
) (10.7±1pA/pF (Control) vs. 1.8±0.7pA/pF (HF)). Inward rectifier K
+
current (I
K1
) inward conductance and peak outward I
K1
were significantly reduced in HF (p<0.05). The rapid component of the delayed rectifier (I
Kr
) was significantly reduced with chronic HF (Panel B). Chronic HF did not alter the slow component of the delayed rectifier current (I
Ks,
p=NS). CONCLUSIONS: In chronic canine non-ischemic cardiomyopathy, the large reductions in I
K1
, I
to
and I
Kr
cause diastolic depolarization and AP prolongation. These alterations may contribute to ventricular tachyarrhythmias during chronic nonischemic HF.
Abstract 562: Adeno-Associated Virus-Mediated Gene Transfer and Activation of Insulin-like Growth Factor-I Increases Cardiac Function in Chronic Severe Heart Failure
Authors: Takahashi Toshiyuki , Lai N. Chin , Gao Mei Hua , Tang Tong , Roth David M , Miyanohara Atsushi , Hammond H. Kirk
Published: April 2024

Background:
Insulin-like growth factor-I (IGF-I) has pleiotropic effects, including positive inotropic, anti-apoptotic, angiogenic and pro-myogenic in the heart. We constructed a serotype 5 adeno-associated virus vector encoding IGF-I under tet-regulation (AAV5.IGFI-tet) to assess the effects of exogenous IGF-I expression on cardiac function in chronic severe heart failure induced by myocardial infarction (MI). We tested the hypothesis that increased cardiac expression of IGF-I would increase the function of the failing heart.

Methods and Results:
Twenty-one 3-month old mice underwent indirect intracoronary delivery of AAV5.IGFI-tet (5x10
11
vp), followed immediately by permanent left coronary artery occlusion. Five weeks later, the 10 mice that survived MI and met entry criteria (LVEF<40% and LV end-diastolic diameter>4.5 mm; echocardiography), randomly were assigned to receive doxycycline in their water supply, which activates cardiac IGF-I expression (IGF-On, n=5) or receive regular water (i.e., no treatment, IGF-Off, n=5). After 5 wk of treatment (10 wk from MI), echocardiography showed that IGF-On mice had increased LVEF while the IGF-Off mice showed continued decline (ΔLVEF, IGF-On: +2.3 ± 2.1%; IGF-Off: −5.6 ± 1.9%, n=5 for each group, p=0.03), and pressure-volume analyses showed increased cardiac output (IGF-On: 6.7 ± 1.1 ml/min; IGF-Off: 4.0 ± 0.3 ml/min, n=3 for each group, p=0.08) and stroke volume (IGF-On: 17 ± 3 μl; IGF-Off: 9 ± 1 μl, n=3 for each group, p=0.05). Rates of apoptosis, assessed by TUNEL staining, were reduced in viable LV (Border zone, IGF-On: 125 ± 5 /10
5
nuclei, n=3; IGF-Off: 416 ± 40 /10
5
nuclei, n=4, p<0.02; Remote zone, IGF-On: 85 ± 7 /10
5
nuclei, n=3; IGF-Off: 207 ± 28 /10
5
nuclei, n=4, p<0.01).

Conclusion:
Increased cardiac expression of IGF-I improves LV function and reduces apoptosis in the failing heart. These data suggest a new potential treatment strategy for severe heart failure.
Abstract 564: Xenograft of Human Mesenchymal Stem Cells to Canine Myocardial Infarction Model with or without Epicardial Pacing has no Immune Rejection, But Proarrhythmia and Sympathetic Nerve Sprouting
Authors: Pak Hui-Nam , Kim Jin Seok , Fang Yong Hu , Kim Gwang Il , Lim Hong Euy , Ryu Ji Yeon , Kim Byung Soo , Hwang Chun , Chen Peng-Sheng , Kim Young-Hoon
Published: April 2024

Background

Cardiac resynchronization therapy reduces morbidity and mortality in patients with heart failure, and mesenchymal stem cells (MSC) transplantation has a potential for the improvement of ventricular function, especially in acute stage of myocardial infarction. However, the safety of combined left ventricular (LV) epicardial pacing (EpiP) and MSC transplantation in acute myocardial infarction (AMI) has not been studied.

Methods and Results

We explored the safety of human MSC (hMSC) transplantation in 15 canine model of with or without AMI or LV EpiP. AMI was made by ligation of proximal left circumflex coronary artery in open chest canine model, and positioned EpiP electrode on the peri-infarct zone (DDD mode, 3.5 V, minimal AV delay 150 ms). Implantable cardioverter defibrillator (ICD) was implanted in right ventricular endocardium to monitor ventricular arrhythmia. hMSC (1x10
7
in 1 mL, 5 sites) were injected subepicardially 15 mm separated from pacing electrode. We compared hMSC+EpiP+AMI (n=5), hMSC+EpiP (n=5), hMSC only (n=5), and sham operation (n=1) by ICD egm analysis and immunohistochemistry after 4 weeks of survival. Results: 1. 80% of hMSC+EpiP+AMI group, 60% of hMSC+EpiP group, 40% of hMSC only group, and none of control revealed spontaneous ventricular tachyarrhythmia (VT) episodes in stored ICD egm, and 60%, 40%, 20%, and 0% of each group died suddenly at 5.3±6.6 days after surgery. 2. Human nucleolin positive hMSC with vimenting positive meosdermal differentiation were observed at the subepicardial peri-infarct zone without any evidence of immune rejection. 3. The hMSC transplanted hearts expressed higher density of tyrosine hydroxylase positive cardiac nerves compared with control dog.

Conclusion
Although hMSC xenograft to canine AMI and EpiP model showed successful engraftment of hMSC without immune rejection, VT and sudden death with sympathetic hyper-innervation happened frequently.
Abstract 4164: Decreased Skeletal Muscle Mitochondrial DNA in Patients on High-Dose Simvastatin Therapy
Authors: Schick Brian , Côté Hélène C , Laaksonen Reijo , Päivä Hannu , Lehtimäki Terho , Frohlich Jiri
Published: April 2024

Background:
Statins are used widely to treat dyslipidemia. Statin-induced myopathy (SIM) is a well-recognized side effect that decreases quality of life and complicates patient management. A reliable and convenient method of diagnosing SIM is needed, as patient self-report and creatinine kinase levels are unreliable and light microscopy of skeletal muscle is inconvenient. Statins have been associated with mitochondrial toxicity, which may be related to mitochondrial DNA (mtDNA) levels; mtDNA levels could be a useful marker of SIM. We studied the effect of high-dose statin treatment on mtDNA levels in human skeletal muscle.

Method:
Skeletal muscle mtDNA to nuclear DNA (nDNA) ratios were measured retrospectively in 86 biopsies obtained from an earlier randomized, double-blind, placebo-controlled trial. Forty-three hypercholesterolemic subjects aged 31 to 69 years were randomly assigned into 3 treatment groups and received placebo (n=14), atorvastatin 40mg/d (n=15), or simvastatin 80mg/d (n=14) for 8 weeks. Biopsy specimens were acquired at baseline and 8 weeks. mtDNA was quantified by extracting total DNA from muscle homogenates then quantifying a nuclear gene (ASPG) and a mitochondrial gene (CCOI) with real-time PCR. Results are expressed as the mtDNA/nDNA ratio. Differences within groups were assessed by the paired
t
-test and differences between groups by ANOVA with repeated measurements.

Results:
mtDNA significantly decreased (47%;
P
=0.0020) in the simvastatin group. Non-significant decreases of 12% occurred in the atorvastatin (
P
=0.24) and placebo (
P
=0.20) groups. Average baseline ratios of the three groups did not differ significantly (
F
=0.655).

Conclusion:
High-dose simvastatin therapy significantly decreased skeletal muscle mtDNA. mtDNA may be a useful marker of mitochondrial toxicity in statin users, but the clinical relevance of our findings needs to be further investigated.
Abstract 190: HSP27 is Sufficient and Required for Prevention of Tachycardia Induced Remodeling in a Cell Model for Tachypacing
Authors: Brundel Bianca J , Qi XiaoYan , Yeh Yung-Hsin , Shiroshita-Takeshita Akiko , Chartier Denis , Henning Robert H , Kampinga Harm H , Nattel Stanley
Published: April 2024

We previously found evidence that heat shock protein (HSP) induction protects against the promotion of atrial fibrillation (AF) by atrial tachypacing-remodeling in dogs. In this study, we evaluated the effect of HSP induction in a tachypaced atrial cell-line (HL-1) model of tachycardia-remodeling.

Methods:
The effects of tachypacing HL-1 myocytes (3 Hz, 0 – 4 hrs) on Ca
2+
transients (CaT) and cell shortening (CS), were studied with and without HSP-inducing pre-treatments like mild heat shock (HS), or the non-toxic inducer geranylgeranylacetone (GGA), transient transfection of human HSP70, HSP27, a phosphorylation deficient mutant HSP27-AAA or the phospho-mimicking mutant HSP27-DDD. Knockdown of HSP27 was performed with short-hairpin forming siRNA.

Results:
In HL-1 myocytes, tachypacing significantly and progressively reduced CaT and CS after 4 hours (Fig A

). HSP induction by HS or GGA protected HL-1 myocytes against suppression of CaT and CS by 4 hours of tachypacing. Protective effects were also seen upon transfection with HSP27 and a phosphorylation-mimicking HSP27 mutant, but not by HSP70 or a non-phosphorylatable HSP27-mutant construct (Fig B

). Knockdown of HSP27 with shRNA prevented GGA-mediated protection (Fig C

).

Conclusions:
Our findings indicate that HSP27 induction protects against AF-promoting remodeling, that the protective effect requires HSP27 phosphorylation, and HSP27 is sufficient for protection. These findings advance our understanding of the biochemical determinants of the protective effects of HSP induction against atrial tachycardia remodeling.
Abstract 4170: Inter- and Intra-Individual Variability in Glycemic Index Values for White Bread Determined Using Standardized Procedures
Authors: Vega-López Sonia , Ausman Lynne M , Jalbert Susan M , Lichtenstein Alice H
Published: April 2024

Glycemic index (GI) values are used to classify carbohydrate-containing foods on the basis of serum glucose response relative to a glucose challenge, and both the GI and glycemic load (GL) values (GI adjusted for total carbohydrate) of diets have been used to estimate chronic disease risk. There is an underlying assumption that GI values for a given food are highly reproducible for an individual and similar among individuals. To test this hypothesis the inter- and intra-individual variability of GI values for white bread were assessed in twenty-three healthy adults (20–70 y) under controlled conditions using up to three sets of two challenges, white bread and glucose, administered in random order. Using the published standard protocol, the GI value was calculated by dividing the 2-h incremental area under the serum glucose response curve (AUC) for 50 g available carbohydrates from commercial white bread by the AUC for 50 g glucose. The mean GI value of the first set was 78 ± 73 (N=23), with an inter-individual coefficient of variation of 94%. The intra-individual reproducibility of the GI value for those subjects who completed three sets (n=14) was calculated using individual AUC values for white bread divided by the mean of the three AUC values after glucose, and were 78 ± 39, 60 ± 17 and 75 ± 37 for tests 1, 2 and 3, respectively. Inter-individual coefficients of variation were 50%, 29% and 50%, respectively. The mean GI value of these three sets was 71 ± 22, with an intra-individual coefficient of variation of 30%. These data suggest that despite the reduction in inter- and intra-individual variability with replicate testing, individual responses to a single food, white bread, are highly variable. Caution should be used in drawing conclusions on the basis of GI or GL values until there is a better understanding of inter- and intra-individual variability in response to individual foods and food mixtures.
Abstract 4173: Statin Use is Associated with Higher Levels of Total and Long-Chain n-3 Fatty Acids and Lower Levels of n-6 and Saturated Fatty Acids in Patients Following Acute Myocardial Infarction
Authors: Nigam Anil , Frasure-Smith Nancy , Lespérance Francois , Julien Pierre
Published: April 2024

Background:
Higher plasma n-3 fatty acid levels are associated with improved long-term outcomes in the primary and secondary prevention of CHD. Besides anti-arrhythmic effects, n-3 fatty acids have been shown to possess other pleiotropic effects including anti-inflammatory and antithrombotic effects in a fashion similar to statins. The effect of statin use on fatty acid synthesis and metabolism has received little attention in CHD patients. The objective of this study was to evaluate the relationship between statin use, plasma fatty acid levels and estimated desaturase activity in patients following acute myocardial infarction.

Methods:
Clinical and metabolic parameters including fasting plasma fatty acid levels were measured in 734 subjects, approximately eight weeks following AMI. Correlations were evaluated between statin use, fatty acid levels and desaturase activity.

Results:
Statin use was observed in 539 of 734 patients and was associated with higher levels of total n-3 (r=0.10, P=0.005) and long-chain n-3 fatty acids (ecosapentanoeic acid r=0.11, P=0.004; docosahexanoeic acid r=0.12, P=0.001) and lower n-6 (linoleic acid r=-0.24, P<0.001) and total saturated fatty acid levels (r=-.083, P=0.025). Multivariate models adjusted for age, sex, smoking, physical activity level and the components of the metabolic syndrome did not significantly alter the observed associations. Statin use correlated negatively with estimated Δ-9 desaturase activity (r=-0.08, P=0.025) and positively with Δ-5 activity (r=0.23, P<0.001).

Conclusions:
Statin use is associated with an improved plasma fatty acid profile characterized by higher levels of total and long-chain n-3 fatty acids and lower levels of saturated and certain n-6 fatty acids. We cannot exclude that dietary factors may have influenced the observed associations. Our data is consistent with basic science investigations and randomized trials in non-CHD patients demonstrating that statins do influence fatty acid synthesis and metabolism. Whether the pleiotropic effects of statins may in part be due to an improved fatty acid profile requires further study in prospective clinical trials.
Abstract 4182: Endogenous Estrogen and Risk of Stroke in Elderly Men: The Honolulu Heart Program
Authors: Rodriguez Beatriz L , Abbott Robert , Wilson Peter W , Launer Lenore J , Ross G W , Masaki Kamal H , Strozyk D , Yano Katsuhiko , Popper Jordan S , Petrovitch Helen , Curb J. D
Published: April 2024

Background
: Little is known about the relationship between endogenous estrogen and the risk of stroke, particularly in elderly men. The purpose of this report is to determine if levels of total and bioavailable endogenous estrogen and testosterone can predict stroke in a population-based sample of elderly men.

Methods
: Endogenous estrogen and testosterone were measured in 2,197 men aged 71 to 93 years who participated in the Honolulu Heart Program from 1991 to 1993. All were free of prevalent stroke, coronary heart disease, and cancer. Participants were followed to the end of 1998 for thromboembolic and hemorrhagic events.

Results
: During the course of follow-up, 124 men developed a stroke (9.1/1000 person-years). After age-adjustment, men in the top quintile of bioavailable estrogen (>82.8 pmol/L [22.6 pg/mL]) experienced a 2-fold excess risk of stroke versus men whose estrogen levels were lower (15.5 vs 7.5/1000 person-years, p<0.001). Among the lower quintiles, there were little differences in the risk of stroke. Findings were also significant and comparable for total estrogen and for thromboembolic and hemorrhagic events. After additional adjustment for hypertension, diabetes, adiposity, cholesterol concentrations, atrial fibrillation, and other characteristics, the relationship between estrogen and stroke between the top versus lower quintiles persisted (relative hazards = 2.2; 95% confidence interval = 1.4 − 3.3, p<0.001). Testosterone was not related to the risk of stroke.

Conclusions
: Findings suggest that high levels of endogenous estrogen are associated with an elevated risk of stroke in elderly men.
Abstract 4194: Low-Dose Aspirin Reduces Cardiovascular Events and All-Cause Mortality Among Patients with Stable Cardiovascular Disease: A Meta-Analysis
Authors: Berger Jeffrey S , Brown David L , Becker Richard C
Published: April 2024

Background:
The Antithrombotic Trialists’ Collaboration meta-analysis demonstrated that anti-platelet therapy reduced cardiovascular events in patients with prior cardiovascular disease. However, in that analysis, stable and unstable patients were grouped together, all anti-platelet agents were combined and most of the aspirin studies used a dose higher than currently recommended (>325mg/day). The effect of low-dose aspirin (50–325mg/day) in patients with stable cardiovascular disease has not been reported.

Methods:
Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a history of myocardial infarction (n=1), stable angina (n=1) and a stroke or transient ischemic attack (n=4). A random effects model was used to combine results from individual trials.

Results:
The 6 studies randomized a total of 9,853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (non-fatal MI, non-fatal stroke and cardiovascular death) (Odds Ratio (OR) 0.79, 95% Confidence Interval (CI) 0.72– 0.88, P<0.01), 26% reduction in the risk of non-fatal MI (OR, 0.74, 95% CI, 0.60– 0.91, P<0.01), 25% reduction in the risk of stroke (OR, 0.75, 95% CI, 0.65– 0.87, P<0.01) and a 13% reduction in the risk of all-cause mortality (OR, 0.87, 95% CI, 0.76– 0.98, P=0.03).Based on these data, treatment of 30 patients with low-dose aspirin is required to prevent 1 cardiovascular event, 83 patients to prevent 1 non-fatal MI, 40 patients to prevent 1 stroke and 71 patients to prevent 1 death. Patients treated with aspirin were significantly more likely to experience severe bleeding (OR, 2.2, 95% CI, 1.4–3.4, P<0.01). The number needed to harm from severe bleeding is 111 patients.

Conclusion:
Among patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, while increasing the risk of severe bleeding. The protective effect of aspirin supports current recommendations that all patients with stable cardiovascular disease be placed on low-dose aspirin.
Abstract 4205: Cardiovascular Risk Profiles Measured at the Same Age in American Immigrant Fathers and Offspring
Authors: Rodriguez Beatriz L , Grove John S , Masaki Kamal H , Donlon Timothy A , Chen Randi , Seto Todd , Quertermous Thomas , Curb J D
Published: April 2024

The changes in risk profiles which occur with immigration to new cultural environments are well known. However, there have been few instances where the magnitude of these changes can be examined by measurements of cardiovascular risk factors in parents and offspring at the same age. Vital statistics indicate that Japanese-Americans in Hawaii have substantially lower CVD (cardiovascular disease) rates than are present in U.S. Caucasians, but markedly higher rates than those seen in Japanese in Japan. The Honolulu Heart Program (HHP) first measured CVD risk in first and second generation Japanese-American men in Hawaii from 1965 to 1968. From 2001 to 2004, similar measures were made in offspring from a random sample of families of these HHP men as part of the NHLBI Family Blood Pressure Program. This analysis uses data from 987 offspring (505 male and 482 female) between 39 to 77 years of age. At the time of examination, the mean age for the fathers was 53.7 years and for the offspring was 56.5 years. For some risk factors, the offspring had lower age-adjusted mean values than their fathers. The mean total cholesterol in the fathers was 218 mg/dl compared to 198.9 mg/dl in sons [p<0.001] and 212 mg/dl in daughters [p<0.001]. Current smoking was seen in 38% of fathers as compared to 15% of sons [p<0.001] and 8% of daughters [p<0.001]. However, for other risk factors, the offspring levels were higher. Hypertension (BP <140/90 or on meds) was present in 39% of fathers as compared to 51% of sons [p<0.001] and 43% of daughters [ns, p=0.27]. The fathers were much leaner, with an age-adjusted mean Body Mass Index (BMI) of 23.9, compared to 27.2 for sons [p<0.0001] and 25.5 for daughters [p<0.0001]. Although defined in slightly different ways in fathers vs. offspring, diabetes was present in 15% of fathers as compared to 24% of sons [p<0.01] and 17% of daughters [ns, p=0.59]. While one must consider temporal trends as well as acculturation in making these comparisons, these data offer remarkable insight into changes in cardiovascular risk which immigrant populations face in the U.S. today.
Abstract 579: Calcium Handling and Mechanisms of Automaticity in Human Embryonic Stem Cell Derived Cardiomyocytes
Authors: Itzhaki Ilanit , Satin Jonathan , Izu Leighton , Schroder Elizabeth A , Schiller Jackie , Balke C. William , Beyar Raphael , Gepstein Lior
Published: April 2024

Human embryonic stem cell derived cardiac myocyte (hES-CM) function is poorly understood. Under normal conditions mature cardiac muscle is quiescent but immature CMs, including hES-CMs display automaticity. In mature nodal cells store Ca contributes to automaticity. Therefore, we tested the hypothesis that cytosolic intracellular store Ca transients in hES-CMs contributes to their spontaneous excitability. Relatively immature hES-CMs were chosen for the study (<40 days differentiation). We used a combination of approaches including RT-PCR, immunocytochemistry, whole-cell voltage-clamp, and simultaneous patch-clamp and laser scanning confocal Ca-imaging of cells co-labeled with di-8-Anepps to delineate surface membrane. hES-CMs reveal two distinct types of Ca transients AP driven global Ca transients (AP-Ca transients) and local Ca transients (LCTs). The LCTs originate at the cell periphery, associated with plasma membrane (PM), do not propagate across the width of the cell and are not interactive with electrical activity. The AP-Ca transients are rhythmic high amplitude events that originate at the PM and spread as a propagated wave to the cell center. Caffeine-releasable store Ca was demonstrated by focal, temporally-limited puffs of caffeine and by long-lasting caffeine depletion of internal store Ca. Spontaneous activity was inhibited by 20 mM caffeine (>20s continual application). Ryanodine caused a progressive decrease in the amplitude of Ca-release and AP rate. Interestingly, 10μM TTX abolishes all Ca transients (AP-Ca transients and LCTs) suggesting that elevated cytosolic Na contributes to the LCTs. High-speed 2D confocal laser scanning imaging showed that LCTs occur out of phase with AP-Ca transients, and separate LCTs within a given cell are often out of phase with one another. This argues against LCTs as a primary rhythm generator in early stage hES-CMs. However ryanodine and caffeine effects argue for internal store Ca requirement for automaticity. We conclude that the molecular mechanism of automaticity in early stage hES-CMs relies on the interplay between AP-Ca and membrane potential. This study provides the first evidence that developing hES-CMs have functional internal store Ca.
Abstract 584: Simultaneous Antagonism of the V2 Receptor with Tolvaptan and Activation of the Natriuretic Peptide A-Receptor with B-Type Natriuretic Peptide: A Novel Strategy to Physiologically Enhance Water and Sodium Excretion Without Adversely Affecting Renal Function in a Canine Model of Congestive Heart Failure
Authors: Costello-Boerrigter Lisa C , Boerrigter Guido , Harty Gail J , Burnett John C
Published: April 2024

Background:
Water and sodium (Na) retention are hallmarks of congestive heart failure (CHF). While widely employed, conventional diuretics may adversely affect renal function. Therefore, physiological strategies that enhance water and Na excretion while maintaining renal function are a high priority. Arginine vasopressin (AVP) increases water reabsorption after binding to the V2 receptor in the collecting duct (CD). In contrast, B-type natriuretic peptide (BNP) decreases Na reabsorption via activation of the NPR-A receptor also in the CD and at higher doses also in the proximal tubule. We hypothesized that coadministration of the V2-receptor antagonist tolvaptan (TLV) and BNP would mediate a potent diuresis and natriuresis without adversely affecting renal hemodynamics in experimental CHF. We also assessed plasma and urinary excretion of AVP.

Methods:
Severe CHF was induced in 2 groups of dogs by tachypacing. On day 11 cardiorenal function was assessed. One group received TLV alone (0.1 mg/kg IV bolus; n=6), whereas the other group received infusion of BNP (50 ng/kg/min) in addition to TLV (n=5).

Results:
Renal hemodynamics were preserved in both groups. TLV alone increased urine flow from 0.07±0.01 to 0.48±0.09 mL/min, while urinary Na excretion (UNaV) remained unchanged. TLV+BNP-50 increased urine flow from 0.17±0.07 to 2.58±0.47 mL/min and UNaV from 1±1 to 77±23 uEq/min while decreasing proximal fractional Na reabsorption (all p<0.05 vs. TLV alone). TLV alone increased plasma aldosterone and distal fractional Na reabsorption, both of which were prevented with BNP-50. In addition, while plasma AVP did not change with TLV or TLV+BNP, urinary AVP excretion markedly increased with TLV+BNP (from 16±5 to 694±196 pg/min) as compared to TLV alone (from 1±1 to 69±23 pg/min).

Conclusions:
TLV and BNP coadministration enhances aquaresis and natriuresis through proximal and distal tubular actions without changing renal hemodynamics. Further, TLV with BNP uniquely enhances urinary elimination of AVP warranting further study. We conclude from these findings in experimental CHF that simultaneously antagonizing the V2 receptor by TLV and activating the NPR-A receptor with BNP may be a novel and physiologic diuretic and natriuretic strategy in overt CHF.
Abstract 585: Activated Vitamin D Attenuates Left Ventricular Hypertrophy and Dysfunction in DAHL Salt-Sensitive Rats
Authors: Bodyak Natalya , Ayus Juan Carlos , Shivalingappa Venkatesha , Rigor Debra , Chen Yee-Shiuan , Ke Quingen , Karumanchi Ananth , Thadhani Ravi , Kang Peter M
Published: April 2024

Introduction:
Cardiovascular disease is the leading cause of death among end-stage renal disease (ESRD) patients. Paricalcitrol (PC), an activated vitamin D analog, is associated with improved survival in patients with ESRD. The mechanism of improved mortality, however, is unclear. We hypothesized that administration of PC would

attenuate the development of cardiac dysfunction in Dahl salt sensitive (DSS) rats following a high salt (HS) diet, and

improve cardiac structure and function in ESRD patients.

Methods:
Male DSS rats were fed a HS diet (6% NaCl) for 6 weeks beginning at 6 wk of age. PC was administered IP at 200 ng 3x/wk. Animals were evaluated for cardiac function, hemodynamics, mRNA expression of ANF, and plasma BNP levels. Also, a cohort of 77 ESRD patients treated with PC and followed for one year was examined for cardiac function by echocardiogram.

Results:
Rats on HS + PC compared with HS + vehicle developed significant decrease in heart weight/body weight (HW/BW) ratio (29%, p<0.05) and lung weight/body weight (LW/BW) ratio (27 %, p<0.05). Echocardiogram analysis revealed that PC treatment lead to significant improvement of fractional shortening compared with HS + vehicle treated animals (52.9±1.0 % vs. 45.7±1.6 %, p<0.05). Furthermore, LV pressure measurement showed that PC treatment resulted in significant improvement of LV end diastolic pressure (46%, p<0.05). In addition, significant increase in plasma BNP level was attenuated by PC treatment (67% reduction, p<0.05). PC treatment also significantly attenuated HS diet induced ANF mRNA increase. PC, however, did not have significant change in mean arterial pressure suggesting that beneficial effect seen by PC is not due to lowering of hypertension. In humans, twelve month echo changes in ESRD patients demonstrated that an improvement in E/A ratio and ejection fraction was associated with increasing dose of PC (p<0.05).

Conclusion:
Administration of PC 3x/week attenuated the development of LVH and LV dysfunction in high salt-induced cardiac hypertrophy and cardiac dysfunction in DSS rats. This finding may also be present in ESRD patients, but these findings remain observational and require confirmation.
Abstract 589: Activation of Toll-like Receptor Induces Cardiac Remodeling
Authors: Yu Qianli , Larson Douglas F
Published: April 2024

Introduction:
Diastolic heart failure, due to increased ventricular stiffness, is brought about by extracellular matrix (ECM) remodeling. We have previously shown that T-lymphocyte function directly affects cardiac fibroblast function and thereby the ECM composition and diastolic function. Oligodeoxynucleotides (ODN) that selectively stimulate the Toll-like receptor-9 (TLR9) receptor on dendritic cells (DC), induce TH1 immune response.

Hypothesis:
Selective stimulation of the DC TLR 9 receptor with ODN CPG1668 activates TH1 lymphocytes resulting in ECM remodeling and diastolic dysfunction.

Methods:
Weight matched C57BL/6J female mice were treated either with PBS (n=8) or with CPG1668 (n=8) at a dose of 50 μg/mouse/week (i.p.) for 4 weeks. After 6 weeks, left ventricular mechanics were determined with pressure-volume loop analysis, ECHO, and ventricular tissue harvested for gene expression, collagen content and crosslinking, and the collagen crosslinking enzymatic activity of lysyl oxidase (LOX). Splenic lymphocytes were harvested for the cytokine determination.

Results:
CPG1668 administration increased the TH1 cytokine, IFN-γ, from 429±21 to 954±21 (ng/10
6
T-cells), while TH2 cytokine, IL-4, decreased from 614±79 to 51±19 (pg/10
6
T-cells). CPG1668 significantly decreased the end-diastolic volume from 18±1 to 14±1μL (P=0.02), and cardiac output from 6.7±0.6 to 4.9±0.6 mL/min (P=0.05) with no change of ejection fraction 71±3 to 73±4 compared with controls. An increase of ventricular stiffness (β), from 0.16±0.01 to 0.23±0.01 mmHg/μL (P=0.0007), was supported by a decreased E deceleration slope of −8.8±0.6 to −4.1±0.4 (P<0.0001). CPG increased total cardiac collagen two-fold (P=0.0004) and collagen crosslinking by 3-fold (P=0.0007) compared with controls. Correspondingly, CPG administration increased cardiac LOX enzymatic activity by 61% (P=0.02). Real time PCR showed that LOXL3 gene expression increased 9.1-fold (P<0.0001) as well as LOX 1.7-fold (P=0.05) when comparing CPG with controls.

Conclusions:
This study demonstrates that stimulation of the TH1 lymphocytes via DC TLR 9 receptor induces cardiac ECM remodeling and diastolic dysfunction associated with LOX induced collagen crosslinking.