bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac output is improved in rats with myocardial infarction by enhancement of respiratory sinus arrhythmia
Authors: O'Callaghan Erin , Lataro Renata , Zhao Le , Ben‐Tal Alona , Nogaret Alain , Paton Julian 
Published: June 2021

Respiratory sinus arrhythmia (RSA) is the physiological modulation of heart rate during respiration. Whilst its physiological function is debated, recent mathematical modelling predicts that RSA saves cardiac energy. Heart failure is associated with a loss of RSA. We aimed to test whether RSA would improve cardiac function in rats 3 days after left ascending coronary artery ligation (post‐MI). Cardiac dysfunction was indicated by infarct size (43±7% of left ventricle) and prolonged systole duration accompanied by reduced peak aortic flow compared to SHAM rats. We built and used a novel central pattern generator (CPG) that, utilizing real‐time diaphragm electromyogram input, generated RSA via respiratory phase‐locked stimulus output to the right cervical vagus nerve. In post‐MI rats, RSA enhancement caused a 12±3% increase in stroke volume, irrespective of the RSA amplitude. Tonic VNS at matched average heart rate increased stroke volume to a similar degree (8±1%, P =0.25 compared to RSA) (n = 7). Despite the increase in stroke volume, myocardial lactate concentrations were unchanged after 45 min of RSA (29±7bpm) or tonic VNS treatment (P = 0.35, One‐way ANOVA). Using a novel CPG device we have demonstrated that, in an acute setting, RSA increases stroke volume in post‐MI rats.British Heart Foundation and Fundação de Amparo à Pesquisa do Estado de São Paulo
Hypertrophy Inducing Factor In Pediatric Idiopathic Dilated Cardiomyopathy Serum
Authors: Sucharov‐Costa Juliana , Sucharov Carmen , Miyamoto Shelley , Walker Lori , Stauffer Brian 
Published: June 2021

IntroductionHeart failure (HF) is a devastating and costly disease that results in about 50% mortality within 5 years of diagnosis. Despite improvements in adult HF outcomes, children with HF have had no substantial improvement in survival over the past 3 decades. Our work has shown that the myocardium of children with idiopathic dilated cardiomyopathy (IDC) demonstrates a gene expression pattern consistent with pathologic remodeling. The objective of this study was to investigate whether serum from pediatric IDC patients would recapitulate this pathologic gene expression pattern in neonatal rat ventricular myocytes (NRVMs).MethodsNRVMs were treated with: 1) whole serum from IDC and non‐failing (NF) control patients; 2) heat inactivated serum; or 3) exosomes isolated from serum. Serum protein identification was performed by mass spectrometry.ResultsTreatment of NRVMs with whole serum from pediatric IDC patients induced a pathologic hypertrophic response that was characterized by changes in gene expression and increase in cell size. These changes were prevented by heat inactivation, indicating a protein factor. Exosome treatment suggests that the observed effect is also mediated by RNAs/miRNAs.ConclusionWe show that circulating factors (RNA and protein) present in the serum of pediatric IDC patients but not in NF controls, induce a pathologic response in NRVMs. Identification of these circulating factors could represent a novel approach to age‐specific HF drug discovery.Source of Research Support: NIH‐NHLBI R01 HL107715 (BLS), APS Undergraduate Summer Research Fellowship (JSC)
Maternal obesity alters gut microbial ecology in offspring of NOD mice
Authors: Zhu Meijun , Kang Yifei , Du Min 
Published: June 2021

BackgroundGut microbiota (GM) are increasingly recognized as a significant factor in the pathogenesis of T1D. High Bacteroidetes/Firmicutes (B/F) is associated with the development of T1D. Previously we reported that maternal obesity (MO) increases the incidence of T1D in the offspring of nonobese diabetic (NOD) mice, and the current study investigated the possible link of GM to the exaggerated insulitis in offspring due to MO.Methods4‐wk‐old female NOD mice were fed either a control or a high fat diet for 8 weeks before mating. Mice were maintained in their respective diets during pregnancy and lactation. All offspring were fed the control diet to 16‐wk‐old.ResultsPyrosequencing examination revealed that GM of offspring born to obese mothers was distinct from those of control mothers. At phylum level, MO increased Bacteroidetes, Defferibacteres and Proteobacteria, while decreased Firmicutes in offspring GM, resulting in increased B/F ratio in GM of obese offspring. Family level analysis indicated that GM of offspring from obese mothers had increased levels of Deferribacteraceae, Bacteroidaceae, Desulfovibrionaceae, Helicobacteraceaev, and Porphyromonadaceae. Reciprocally, the abundance of Rikenellaceae and Lachnospiraceae‐Ruminococcaceae were decreased in offspring from obese mothers. The analysis at the genus level revealed that Bacteriodes, Barnesiella, Desulfovibrio and Mucispirillum were more abundance, while Alistipes, Clostridium XIVa, Dorea and Osillibacter were less abundance in offspring of obese mothers.ConclusionMO resulted in a dysbiosis in offspring, suggesting a GM‐mediated mechanism on diabetogenesis by MO (NIH R15HD073864).
Regulation of VEGFR2 Activation in Skeletal Muscle by VEGF Isoforms with Differential ECM‐ and NRP1‐Binding: a Computational Study
Authors: Clegg Lindsay , Mac Gabhann Feilim 
Published: June 2021

Tissues expressing only single isoforms of vascular endothelial growth factor (VEGF) form vascular networks that are structurally and functionally different. While the extracellular matrix (ECM)‐ and Neuropilin‐1 (NRP1)‐binding properties of the VEGF isoforms are known, the mechanism by which different isoforms lead to differential signaling downstream of VEGF receptor 2 (VEGFR2) is not well understood. Our objective is to extend a previously developed cell‐level model of VEGFR2 ligation, intracellular trafficking, and site‐specific phosphorylation to a whole‐body framework to study the implications of the ECM‐ and NRP1‐binding properties of VEGF isoforms in vivo. We include two VEGF receptors (VEGFR1 & VEGFR2), one coreceptor (NRP1), one soluble receptor (sVEGFR1), four isoforms of VEGF, and two isoforms of placental growth factor. We find that that distribution of VEGF isoforms in the body is controlled by the ECM‐binding properties of the ligands. We predict that the balance of NRP1‐binding and non‐NRP1‐binding isoforms alters the intracellular distribution of VEGFR2, and thus the relative activation on tyrosines 1175 and 1214, which control the cell behaviors of proliferation and migration/branching, respectively. We investigate changes in the predicted VEGFR2 activation pattern after application of pro‐angiogenic therapies including a VEGF isoform with very strong ECM‐binding. We show that the ECM‐ and NRP1‐ binding properties of VEGF and PlGF isoforms dictate their distribution in skeletal muscle, as well as their receptor‐binding and activating effects.Funding: DoD NDSEG Fellowship (LEC), NIH R01HL101200 (FMG), NIH R00HL093219 (FMG), Sloan Research Fellowship (FMG)
Aortic Pulse Wave Characteristics In Postmenopausal Women With And Without A History Of Hypertensive Pregnancy
Authors: Shepherd John , Harvey Ronee , Ranadive Sushant , Miller Virginia , Joyner Michael , Barnes Jill 
Published: June 2021

<a name=“OLE_LINK2”></a><a name=“OLE_LINK1”>Hypertensive pregnancy (HP) disorders have been linked to a four‐fold increased risk for development of future cardiovascular diseases. We examined whether history of HP in postmenopausal women (N=20, 59±5 yr) influenced the risk factors for cardiovascular disease as assessed by aortic pulse wave characteristics, compared to age and parity matched controls (N=18, 60±4 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity pressure waveforms obtained from SphygmoCor applanation tonometry using the radial artery. Aortic systolic and diastolic blood pressure (ASBP, ADBP), aortic augmentation index (AIx), augmented pressure (AP), aortic pulse pressure (APP), and left ventricular wasted energy (Ew) were calculated from the generated aortic pressure waveform. There were no differences in ASBP (125±4 vs. 129±4 mmHg), ADBP (79±2 vs. 81±2 mmHg), AP (17±2 vs. 17±2 mmHg), AIx (35±2 vs. 29±1%), AIx @75BPM (31±2 vs. 29±1%), Ew (3313±338 vs. 3364±432 dynes/cm2/s), between women with a history of HP vs. matched controls, respectively (P>0.05 for all). Body mass index was significantly higher in women with a history of HP (30.6±1 vs. 26.7±1 kg/m2, P<0.05), however it did not statistically influence any of the indices (P>0.05 for all). Our results suggest that postmenopausal women with a history of HP do not demonstrate elevated aortic blood pressure or altered aortic pulse wave characteristics in comparison to matched controls. </a>Supported by: National Institute of Aging 1P50AG044170‐01 and CTSA UL1 TR000135 and HL 118154
Graded Venous Occlusion of the Lower Limbs Contributes to the Exercise Pressor Response in Healthy Humans
Authors: Cowl Andrielle , Keller‐Ross Manda , Cross Troy , Rebollo Naomi , Maria Rios Jose , Johnson Bruce , Olson Thomas 
Published: June 2021

BackgroundLocomotor muscle group III/IV afferent feedback contributes to sympathoexcitation. Sub‐systolic lower limb occlusion may stimulate this reflex.
PurposeTo examine the cardiovascular response to lower limb venous occlusion in healthy humans during rest and exercise.MethodsNineteen adults (9 men, 25±5 yr; mean±SD) participated in two visits. V1: 3 min seated rest followed by randomized bilateral thigh tourniquet inflation to 20, 40, 60, 80, 100 mmHg for 2 min with 2 min deflation between occlusions. V2: Recumbent cycle ergometer exercise at 30% peak work with occlusion described in V1. We measured mean, systolic and diastolic pressure, cardiac output, heart rate, and stroke volume (MAP, SBP, DBP, CO, HR, and SV, respectively).
ResultsAt rest, MAP (85±18 mmHg) increased at 100 mmHg (Δ4±5, p<0.05) mediated by increased DBP (71±15 mmHg) at 100 mmHg (Δ5±4, p<0.05) with no change in SBP. During exercise, MAP (89±11 mmHg) increased at 60 (Δ7±7), 80 (Δ14±8), and 100 (Δ16±8) mmHg occlusions via increased SBP (133±22 mmHg) at 60 (Δ12±14), 80 (Δ20±13), and 100 (Δ26±13) mmHg and DBP (68±9 mmHg) at 60 (Δ5±5), 80 (Δ10±7), and 100 (Δ12±7) (p<0.05, all). Although, CO and SV did not change, HR (108±11 bpm) increased at 40 (Δ5±4), 60 (Δ8±5), 80 (Δ13±7), and 100 mmHg (Δ15±7) (p<0.05, all).ConclusionStimulation of locomotor muscle group III/IV afferents via sub‐systolic occlusion contributes to cardiovascular control.
Skeletal Muscle Afferent Inhibition Improves Exercise Tolerance in Heart Failure
Authors: Keller‐Ross Manda , Carlson Alex , O'Malley Kathy , Bruhn Eric , Wolhart Sarah , Johnson Christopher , Eisenach John , Curry Timothy , Joyner Michael , Johnson Bruce , Olson Thomas 
Published: June 2021

BACKGROUNDIncreased activation of Group III/IV skeletal muscle afferents is suggested to play a role in exercise intolerance in heart failure (HF).PURPOSEThe purpose of this study was to examine if skeletal muscle afferent feedback inhibition improves exercise tolerance in HF.METHODS8 HF patients [59±8 yr, mean±SD] participated in two randomized incremental recumbent cycling exercise sessions to peak capacity (peak oxygen consumption, VO2). Session 1: The synthetic opioid fentanyl (50 mcg), known to block afferent feedback, was injected intrathecally (INJ) in the lumbar spine (L3‐L4 intervertebral space) prior to exercise. Session 2: Participants were prepared similarly with a sham injection (placebo, PLA). Gas exchange, dyspnea and RPE were measured.RESULTSHF patients exercised for a longer duration (Δ3±3 min, p=0.02) and reached a higher power output (PLA:109±30 vs. INJ:128±34 W, p=0.02) with locomotor afferent inhibition. Additionally, peak VO2 was non‐significantly greater (PLA:18.7±3.3 vs. INJ:21.8±4.4 ml/kg/min, p=0.10). With INJ workload matched to peak PLA workload, RPE was reduced (PLA:18±2 vs. INJ:15±2, respectively, p=0.005) and dyspnea was lower (PLA:7.5±2 vs. INJ:4.2±1, p=0.003) with no difference in VO2 (p>0.05).CONCLUSIONInhibition of group III/IV locomotor muscle afferent feedback contributes to improved exercise tolerance and exertional symptoms in HF patients.
A Pilot Exercise Intervention to Enhance Fitness and Quality of Life among African American and White Colorectal Cancer Survivors
Authors: Williams Brian , Maxwell Nicholas , Cook Jennifer , Mahoney Martin , Ray Andrew 
Published: June 2021

As the third most common occurring malignancy and 3rd leading cause of cancer‐related mortality, colorectal cancer (CRC) represents an important public health concern. Substantial disparities exist for CRC with elevated incidence and relative survival rate among African Americans (AA) compared to Caucasians (C).PurposeTo determine the feasibility of recruiting AA and C subjects into a training intervention study to improve physiologic and quality of life measures.MethodsSubjects interested in participation were sent letters describing the study, they were then called and if interested, pre‐screened over the phone prior to consenting to assess eligibility. If deemed potentially eligible based on the pre‐screening, subjects then completed two screening visits followed by twelve weeks of progressive exercise training on a cycle ergometer.ResultsOut of the 241 letters sent, AA and C subjects had a 86% (n=112) and 96.7% (n=118) attrition rate for phone screening. Of those screened, AA and C had 66.7% (n=12) and 75% (n=3) that were eligible to begin the training. After ten months of recruitment, there have been two (1.5 % of those sent letters) AA subjects that have completed the training and one C (0.8% of those sent letters) subject.ConclusionSubject recruitment for a twelve week intervention training study has a very high attrition rate for both AA and C. Completion of a twelve week training after recruitment may be more difficult for African Americans compared to Caucasians.
The Carotid Baroreflex Modulates the Inflammatory Response to Escherichia Coli Lipopolysaccharide (LPS) ‐ Induced Endotoxemia
Authors: Favaro Laura , Domingos Gean , Santos‐Almeida Fernanda , Castania Jaci , Fazan Rubens , Salgado Helio 
Published: June 2021

Our aim was to examine the modulatory effect of electrical activation (EA) of the carotid baroreflex upon the inflammatory responses elicited by LPS. Wistar rats were divided into 3 groups: 1) Control (Saline); 2) LPS; 3) LPS + EA. The subjects were implanted with electrodes around the carotid sinus and catheters into the femoral artery and jugular vein. The surgical procedures were performed under ketamine/xylazine anesthesia. On the next day, the arterial pressure (AP) and heart rate (HR) were recorded, in conscious rats, followed by saline or LPS (1.5 mg/kg iv) administration combined with EA (1mA; 1ms; 30Hz) of the carotid sinus for 1h. Plasma was collected 1, 2 and 3 hs after saline or LPS administration, while the spleen and the heart were collected after 3 hours, to quantify interleukin 6 (IL‐6), 10 (IL‐10), 1β (IL‐1β) and tumor necrosis factor (TNFα). EA did not change the AP or HR, but reduced (LPS vs LPS+EA) inflammatory cytokine TNF‐α (283±139 vs 115±72 pg/µL at the1st h), IL‐6 (11310±1521 vs 3397±709 pg/µL at the 3rd hour) and IL‐1β (296±24 vs 107±29 pg/µL at the1st h), while increased anti‐inflammatory cytokine IL‐10 (25±9 vs 83±25 pg/µL at the 3rd hour). EA reduced IL‐1β (1.66±0.44 vs 1.24±0.14 pg/µg of protein) and increased IL‐10 (0.89±0.08 vs 1.12±0.05 pg/µg of protein) in the spleen, while reduced the IL‐6 (6.43±1 vs 2.88±0.42 pg/µg of protein) and increased IL‐10 (0.8±0.1 vs 1.05±0.14 pg/µg of protein) in the heart. We concluded that electrical activation of the carotid baroreflex, in conscious rats, reduced pro‐inflammatory and increased anti‐inflammatory cytokines, modulating the inflammatory response elicited by LPS.Financial Support: FAPESP, CAPES and CNPq.
Mechanisms of Folding upon Binding
Authors: Clarke Jane 
Published: June 2021

Investigating families of intrinsically disordered proteins that fold upon binding. One particularly useful approach for investigating protein folding is 'to investigate the folding of several topologically, structurally and/or evolutionarily related proteins in order to discern patterns and trends in folding (stability, pathways and mechanisms). We are now applying this approach to the folding of intrinsically disordered proteins. The systems we are studying all involve formation of helical structure when a disordered protein binds its target. The properties of these systems are vastly different, binding affinity ranges from µM – nM and association and disassociation rate constants vary by many orders of magnitude. This brings different challenges for determining the kinetics of assembly and disassembly. We are investigating some fundamental questions in the IDP field: How important is residual structure in the IDP‾ How do regions outside the binding site influence binding‾ What are the mechanisms of binding‾ What role does the partner protein play in determining the binding mechanism and the strength of binding‾ Can we relate biophysical properties to specific IDP functions‾ I will discuss our latest findings.
Ripened Cheddar Cheese Peptides Protect Human Vein Endothelial Cells (HUVEC) Against Expression Of Risk Markers For CVD: Role Of Paroaxonase‐2 (PON‐2) As Peptide Molecular Target
Authors: Ravisankar Shreeya , Noratto Giuliana 
Published: June 2021

Cardiovascular diseases (CVD) are a major cause of death around the world and dietary bioactive compounds can protect against the risk of CVD. Our objective was to investigate the effects of ripening length on activity of peptides in protecting HUVEC against inflammatory conditions related to CVD.Peptides extracted from 0,6 and 12 months (mo) ripened cheese were assessed for antioxidant activity by scavenging 2,2′‐azinobis (3 ethyl benzothiazoline)‐6‐sulphonic acid assay. Molecular markers relevant to CVD were investigated in HUVEC treated with peptides (100 μg/mL) using standard molecular biology techniques.Results show that 6 and 12 mo peptides increased antioxidant activity to 4.1‐ and 3.6‐fold of 0 mo. This might have contributed to decrease in production of reactive oxygen species and H2O2 levels in HUVEC challenged with Escherichia coli lipopolysaccharides (LPS) down to levels of controls not challenged with LPS. The 6 and 12 mo peptides upregulated PON‐2 mRNA (1.2‐ and 1.6‐fold of LPS control) and protein levels. This was accompanied by upregulation of glutathione‐S‐transferase (GST) mRNA (to 2.4‐ and 4.4‐fold of LPS control) and activity (to 1.5‐ and 1.2‐fold of LPS control). The role of PON‐2 as molecular target of cheese peptides was confirmed by siRNA interference. The 6 and 12 mo peptides upregulated PON‐2 protein expression and GST activity in PON‐2 knock down cells at similar extent, while downregulating NF‐κB pro‐inflammatory transcription factor. Overall, these results strongly suggests that cheese peptides modulate PON‐2, an important antiatherogenic and antioxidant molecular target relevant to CVD, though increasing ripening period beyond 6 mo does not alter this effect.
Factors Associated with Misreporting of Energy Intake in Food Records: A Validation Study with DLW in Brazilian Low Income Adults
Authors: Lopes Tais , Hoffman Daniel , Ferrioli Eduardo , Luiz Ronir , Sichieri Rosely , Pereira Rosangela 
Published: June 2021

ObjectiveTo assess the magnitude of underreport of energy intake (EI) obtained with food records (FR) in low–income adults, and characteristics associated.MethodsThe studied group included 84 adults (20 ‐ 60 years old). Energy expenditure (EE) was estimated using the Doubly labelled water (DLW) method. To define misreporting, the 95% limits of agreement were used. Student T‐test was applied to evaluate differences in the magnitude of misreporting according to exploratory variables (p<0.05).
ResultsThe limits indicating under and over report were 0.62 and 1.32 for the ratio EI/EE. Underreport of EI was observed in 29% of the participants. In average, UR energy was about 30%. Men presented smaller magnitude of underreported (UR) EI than women. The proportion of UR was higher among less educated participants compared to those who had at least 8 years of education (‐37% vs. ‐25%; p=0.02). Individuals with irregular meals profile showed greater magnitude of UR when compared to those that reported having regularly the main meals (‐46% vs. ‐28%; p=0.03). There was a greater chance of EI underreporting among individuals that regularly replaced lunch or dinner by a snack (OR: 4.5; CI95%: 1.3; 16.1).
Sleep and ultra‐processed intake in early childhood: a longitudinal analyses
Authors: Rauber Fernanda , Vitolo Marcia , Taveras Elsie 
Published: June 2021

ObjectiveTo assess whether shorter sleep at preschool age predicted the higher intake of energy and ultra‐processed food in childhood.MethodsCohort study conducted with 345 Brazilian children of low socioeconomic status aged 3‐4 years and 7‐8 years. Dietary data were collected through two 24‐hour recalls and children's ultra‐processed foods intake was assessed. Mothers reported the number of hours that the children had slept the past 24h.ResultsTotal energy intake at preschool and school‐age was significantly higher in shorter‐sleeping children, with children who slept <10h/d consuming an average of 117 kcal/d (95% CI: 50–184) more than those sleeping for >10 h/d at 3‐4 years; and an average difference of 62 kcal/d (7–117) at 7‐8 year. Regarding changes in diet from pre‐school to school‐age, total energy increased by 54 kcal/d (19–91) and 19 kcal/d (‐66–104) in children who slept 蠅10 and <10 h/d at preschool age, respectively. Intake of energy from ultra‐processed foods increased only in those children who slept <10 h/d. Energy provided by ultra‐processed foods remained constant in children who slept 蠅10 h/d.

Dietary variables
Sleep duration at 3‐4 years

≥10 hours/day
&lt;10 hours/day

mean±SD

At 3‐4 years

Total energy intake (kcal)
1492±253
1610±372*

% energy from ultra‐processed foodsa
45.1±6.1
31.4±4.9*

At 7‐8 years

Total energy intake (kcal)
1548±195
1611±513

% energy from ultra‐processed foodsa
47.7±9.2
48.5±8.8

mean difference (95% CI)

Difference between 7‐8 years and 3‐4 years

% energy from ultra‐processed foodsa
2.4 (0.9—3.9)
17.0 (14.6—19.4)**

* p&lt;0.05, Paired t test. ** p&lt;0.01, Wilcoxon test. a Sweets, savory and biscuits, soft drink, processed meat, and bread.

ConclusionEarly shorter sleep duration was associated with higher energy intake and increased consumption of ultra‐processed foods in children. These findings add new evidence to the limited literature available with children on the role that shorter sleep duration may play in relation to intake.CNPq, CAPES/Brazil.