bluuebunny/crossref_metadata_2025_split huggingface dataset:
INCRETIN AMELIORATES DIABETIC MICROANGIOPATHY IN HEART BY ACTIVATION OF AUTOPHAGY VIA PKA/AMPK AXIS.
Authors: Bando Yasuko , Monji Akio 
Published: June 2021

IntroductionThe incretin hormone glucagon‐like peptide‐1 (GLP‐1) restores diabetic myocardial remodeling observed in type 2 diabetic mice (T2DM); however, it remains unclear whether GLP‐1 may modulates angiogenic activity in diabetic heart.HypothesisWe evaluated the impact of GLP‐1 receptor activation on angiogenesis and its link to endothelial autophagy under diabetic condition.MethodsT2DM mice were treated with Ex4 (24 nmole/kg/day for 4 weeks). Cardiac capiary density was measured by CD31 immunohistological staining. Cultured ECs were used for in vitro experiments. Analyses for the changes in autophagy (LC3‐turnover assay and protein levels of p62 and Beclin1), and angiogenesis (tube formation assay and Akt/AMPK/eNOS activity), were evaluated with or without molecular‐targetted knockdown by RNA interference (siRNA).ResultsT2DM exhibited reduced cardiac capillary density in diabetic heart, which was restored by Ex‐4 with increase in myocardial cyclic AMP concentration. GLP‐1 receptor expression in ECs was confirmed by immunoblot and QPCR. Ex‐4 and PKA enhancers (10 μM forskolin and 1 mM 8‐bromo‐cyclic AMP) facilitated angiogenesis and autophagy in ECs. PKA/AMPK/eNOS phosphorylation levels in ECs were enhanced by Ex4, but each Akt activity remains unchanged. PKA inhibitors (H89, RP‐cAMP, and siRNA for PKA) abrogated the increase in AMPK/eNOS phosphorylation induced by Ex‐4. Tube formation assay revealed that Ex4 enhanced in vitro angiogenesis which were abrogated by inhibition of autophagy and AMPK activity.ConclusionsGLP‐1 receptor activation by Ex‐4 restores impaired angioogenic activity in diabetic heart via the PKA/AMPK‐dependent endothelial autophagic activation.
EVALUATION OF LEFT VENTRICULAR FUNCTION IN RATS TREATED WITH NANDROLONE DECANOATE SUBMITTED TO EXERCISE OF WEATHERED
Authors: NASCIMENTO Andrews , LIMA EWELYNE , BRASIL GIRLANDIA , CALIMAN IZABELA , BISSOLI NAZARÉ , ANDRADE TADEU 
Published: June 2021

There are several evidences of cardiovascular damage by use anabolic steroids androgenic (AAS). However, little is known about the cardiac effects of abusive use of AAS by women. Aim of this study was to evaluate the influence of Nandrolone Decanoate (ND) treatment over cardiac function in female rats submitted to a resistance exercise training. Female Wistar rats was divided in four groups (n=8): Sedentary vehicle (S), sedentary treated (SD), exercise vehicle (E) and exercise treated (ED). The animals were treated with ND (20 mg/kg/week) or vehicle (peanut oil) for 28 days, approved by the Ethics Committee in Animal Experimentation of the UFES (031/2012).The results showed that ND promoted cardiac hypertrophy (area of myocytes, S:11421±312, SD:13304±233, E:12262±198 and ED:13418±153, p<0.01), (number of myocytes, S:7.8±0.2, SD:4.0±0.1, E:5.7±0.2 and ED:3.8±0.1, p<0.01) without modifying, HR, MAP and DAP, but increase intraventricular pressure (PVE; S:99.23±6.36, SD:137.06±5.56, E: 101.22±10.45 and ED:117.29±7.54 mmHg, p<0.01). The evaluation of left ventricular contractile indices shows that the values +dP/dt (S:5240.00±525.56, SD:8654.55±415.73, E:5239.14±160.56 and ED:6443.97±214.50 mmHg/s, p<0.01) and ‐dP/dt (S:‐2590.43±330.09, SD:‐5263.04±319.45, E:‐2502.83±225.32 and ED:‐3492.38±282.12 mmHg/s, p<0.01) were higher in the treated groups. Treatment with ND in female rats promoted cardiac hypertrophy and was able to change the cardiac function particularly with respect to contraction and diastolic function.

Groups
S
SD
E
ED

MAP
106±3
100±4
108±4
110±3

HR
355±12
361±7
353±7
353±1

DAP
86±3
88±5
86±4
87±3

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Neuregulin‐1β Alters the Context‐dependent Production of Immunomodulatory Factors in Human Ventricular Fibroblasts
Authors: Galindo Cristi , Sengsayadeth Seng , Tikhomirov Oleg , Ryzhov Sergey , Sawyer Douglas 
Published: June 2021

Neuregulin‐1β (NRG‐1β) is a growth and survival factor critical for cardiac development and repair. We recently showed that NRG‐1β reduces cardiac fibrosis in infarcted swine and reduces basal and tumor necrosis factor β (TGFβ)‐induced α‐smooth muscle actin (α‐SMA) expression. In normal human ventricular fibroblasts, we also found that NRG‐1β caused a reduction in TGFβ‐induced α‐SMA, but we did not observe significantly lower α‐SMA levels in response to NRG‐1β under basal conditions. We thus hypothesized that the anti‐fibrotic effects of NRG‐1β might be context dependent. Indeed, when primary rat cardiac fibroblasts were cultured on softer substrates NRG‐1β had little effect on α‐SMA expression. NRG‐1β did not alter fibroblast collagen gel contraction in the presence or absence of TGFβ, nor did NRG‐1β treatment alter proliferation or viability of rodent or human fibroblasts. Nonetheless, these cells expressed all three NRG‐1β receptors (ErbB2, 3, and 4), and NRG‐1β alone reduced transcript levels of tumor necrosis factor‐α (TNF‐α) and prominin 1 (CD133) after 2 hours of treatment in the absence of serum. NRG‐1β inhibition of CXCL10, HLA‐DQB1, and adiponectin (ADIPOQ) on the other hand required the presence of TGFβ, as did NRG‐1β‐mediated increase of the TGFβ‐signaling inhibitor SMAD7. Most interesting was the induction of IL10 transcription in response to the combination of NRG‐1β and TGFβ, neither of which had any effect on IL10 transcript levels in the absence of the other. These results suggest that NRG‐1β modulates inflammation via cardiac fibroblast signaling and moreover that these signaling events are context‐dependent.Work was supported by the NIH (K01 HL121045; U01 HL100398).
Investigating the Effect of Inhibiting 'Reactive Oxygen Species' on Intracellular Signaling Pathways in Endothelial Cells
Authors: Ashworth Isa , Obeidat Yasin , Puentes Laura , Torina Anali , Shafique Ehtesham , Abid Ruhul 
Published: June 2021

ObjectiveElevated Reactive Oxygen Species (ROS) in Endothelial Cells (EC's) have been implicated in the pathogenesis of cardiovascular diseases, and much research has gone into elucidating the mechanisms through which oxidative stress leads to these diseases. Research in the last decade, however, has uncovered the central role lower levels of ROS play in physiological intracellular signaling pathways, such as those stimulated by Vascular Endothelial Growth Factor (VEGF) and Tumour Necrosis Factor‐α (TNF‐α) in EC's. Our objective in this study was to determine the effect of a lack of ROS in EC's on the intracellular signaling pathways stimulated by VEGF and TNF‐α.MethodsThe activity of these pathways can be measured by the expression of key downstream proteins that are common to these two pathways such as Akt, ERK‐1/2, IKKα/B, AMPK, eNOS, mTOR and FOXO1. To investigate these pathways in vitro, Bovine Endothelial Aortic Cells (BAEC's) were treated with ROS inhibitors (NAC, DPI) and then exposed to VEGF or TNF‐α to stimulate their respective pathways. Protein was then extracted and transferred to a membrane by Western Blotting then visualized by immunoflourescence.ResultsWestern blots demonstrated that reduction of ROS levels by NAC inhibited VEGF‐induced Akt phosphorylation but not phosphorylation of ERK1/2 in BAEC. The findings of TNF‐induced signaling activation were not conclusive.ConclusionWhereas VEGF‐mediated activation of PI3K‐Akt activation requires ROS, ERK1/2 activation is independent of ROS in ECs.This research was funded by National Institutes of Health (NIH) and American Heart Association (AHA) grants.
Assessment of Cardiac Function Using Pressure Volume Loops in Rbm20‐/‐ Rats
Authors: Sanchez Walk Andrea , De Loera Denise , Bosch Luiza , Guo Wei , Ren Jun , Chew Herbert 
Published: June 2021

RNA binding motif 20 (Rbm20) is a muscle‐specific splicing factor that mainly regulates isoform transition of titin, a giant sarcomeric protein responsible for diastolic properties of the heart. Rbm20‐/‐ (KO) rats fail to splice titin from fetal to adult isoforms, resulting in less stiff ventricular walls and thus systolic dysfunction and heart failure. Although previous data have shown that ejection fraction in KO rats is significantly lower than that of Rbm20+/+ (WT) rats in 10 m old rats, little is known of cardiac function in KO rats versus age‐matched WT rats with development using pressure volume loop analysis. We hypothesized that KO rats would develop dysfunction early in life. Preliminary results of 6 m old rats (n=8 per group) show significant (p<0.05) decreases in cardiac output (KO 18.6±2.1; WT, 43.0±2.9 mL•min‐1), heart rate (KO, 215.0±12.9; WT, 274.4±18.5 b•min‐1), stroke volume (KO, 85.2±4.9; WT, 156.9±3.3 µL), ejection fraction (KO, 30.2±5.0; WT, 53.5±6.6 %), stroke work (KO, 6.17±0.60; WT, 13.0±0.80 mmHg•mL), and cardiac efficiency (KO, 0.464±0.031; WT, 0.655±0.073). End‐systolic elastance was significantly lower in KO (KO, 0.405±0.094; WT, 0.825±0.063 mmHg•µL‐1), indicating an increase in systolic compliance, while neither end‐diastolic elastance (KO, 0.095±0.030; WT, 0.040±0.003 mmHg•µL‐1) nor Tau (KO, 13.5±1.48; WT, 12.8±0.85 ms), both indexes of diastolic compliance, were different. We conclude that KO rats show significant evidence of heart failure as early as 6 m of age.Supported by NIH P20 GM103432, the University of WY Agricultural Experimental Station, and USDA‐NIFA.
Microvascular Dysfunction is Evident in the Cutaneous Circulation of Psoriatic Patients
Authors: Alba Billie , Greaney Jody , Ferguson Sara , Alexander Lacy 
Published: June 2021

Vascular dysfunction in conduit and resistance vessels is evident in adults with plaque psoriasis, a chronic systemic inflammatory disease. However, potential impairments of cutaneous microvascular function in psoriatic patients remain incompletely understood. We hypothesized that microvascular function would be impaired in the cutaneous circulation (non‐lesional) of psoriatic patients. One intradermal microdialysis fiber was placed in the forearm skin of 5 healthy adults (NP: 1M, 4F; 49 ± 1 yr) and 5 adults with moderate (>5% body surface area affected) plaque psoriasis (P: 1M, 4F; 48 ± 1 yr). The site was perfused with lactated Ringer's while red blood cell flux was measured using laser‐Doppler flowmetry during standardized local heating (42°C) to elicit eNOS‐dependent vasodilation. NO‐dependent vasodilation was further quantified after the perfusion of 20 mM L‐NAME (nonspecific NO‐synthase inhibitor). Data were expressed as a percentage of maximum cutaneous vascular conductance (%CVCmax; 28 mM SNP). The local heating‐induced plateau was attenuated in psoriatic patients (NP: 99 ± 1 %CVCmax vs. P: 75 ± 9 %CVCmax; p<0.05). Quantified eNOS‐dependent vasodilation appears to be reduced in the psoriatic group (NP: 57 ± 8 %CVCmax vs. P: 41 ± 8 %CVCmax; p=0.15). These preliminary results suggest that microvascular dysfunction is evident in psoriatic patients and may be mediated by reduced NO bioavailability. Further, the assessment of cutaneous vascular function has particular relevance for this clinical population because the skin‐related symptomology represents the outward manifestation of this systemic inflammatory disease process.FUNDING: Penn State College of HHD Grant
Predictors of Walking impairment in Patients With Claudication Using Linear & Non‐Linear Models
Authors: Abraham Pierre , Feuilloy Mathieu , Mezdad Tininhan , Chauvet Pierre , Schang Daniel 
Published: June 2021

ObjectiveTo identify new variables associated to maximal walking time on treadmill (MWT) in patients with claudication.MaterialWe retrospectively analysed data of 1120 patients referred for transcutaneous exercise oxymetry (TcpO2).MethodsThe outcome measurement was the absolute walking time (MWT) on treadmill (3.2 km/h, 10% slope). We used linear regression analyses (LRA) and a non‐linear analysis (NLA) combining Support Vector Machines and Genetic Explanatory in 800 patients with the following resting variables: Age, gender, body mass index (BMI), the presence of diabetes (Db), minimal ankle to brachial index at rest (ABI), usual walking speed over 10 m (WS10), Number of comorbid conditions (CMC), smoking behaviour (Smo), resting heart rate (HR), pre‐test glycemia (Gly) and haemoglobin (Hg), beta‐blocker use (BB), and exercise‐derived variables: minimal value of pulse oxymetry (Sat), resting chest tcpO2 (TcpO2‐rest), decrease in chest tcpO2 during exercise (DCT), presence of buttock ischemia defined as a DROP index < ‐15 mmHg (Butt‐I).ResultsIndependent variables associated to MWT, by decreasing importance in the models, were : ABI, Age, BMI, WS10m, DC‐TcpO2, Smo, Butt‐I, Gly, HR for the NLA, and Age, ABI, WS10; TcpO2‐rest, BMI, Smo, Butt‐I, HR and BB for the LRA (r=0.518; p<0.01). Gender, Db, CMC, Hb, Gly and Sat were not detected as significantly associated to MWT on treadmill with the LNA and LRA models. Testing of models against MWT over 320 new patients gave r=0.509 for LRA and 0.575 for NLA (both p<0.05).ConclusionsIn addition to ABI, Age, BMI and Smo were found new variables associated to MWT : Butt‐I, HR and WS10.
Carotid Body Ablation Reverses the Hypertension and Autonomic Changes Induced by Intermittent Hypoxia
Authors: Del Rio Rodrigo , Andrade David , Iturriaga Rodrigo 
Published: June 2021

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea syndrome, enhances carotid body (CB) chemosensory discharges in normoxia, eliciting sympathetic overactivation and hypertension. We propose that the enhanced CB chemosensory drive plays a crucial role in the generation of the hypertension during CIH. To study the origin of higher blood pressures during CIH, we performed selective ablation of the CB once animals became hypertensive following CIH exposure. Male Sprague‐Dawley rats (200 g) were exposed to CIH (5% O2, 12 times/h, 8 h/day) and arterial blood pressure (BP) was measured with radiotelemetry. After 3 weeks of CIH, under anesthesia both CBs were cryogenically destroyed with an ice cold needle, and rats were kept one more week in CIH. The effectiveness of this maneuver was confirmed by the disappearance of the ventilatory response to NaCN. After 3 weeks of CIH exposure, rats displayed hypertension (BP~10 mmHg), enhanced hypoxic ventilatory response and reduced baroreflex sensitivity (BRS) from 2.28±0.05 to 1.76±0.10 ms/mmHg. The ablation of the CBs markedly decreases the elevated BP, reduced the enhanced ventilatory response to hypoxia and normalized BRS to 2.52±0.12 ms/mmHg. We found that the cardiorespiratory alterations induced by CIH are critically dependent on functional CB chemoreceptors. Also, our results showed that the CIH‐induced hypertension was abolished by ablation of the CB despite the continuous exposure to CIH stimulation. Thus, our results indicate that the CB plays a pivotal role in the progression and maintenance of the CIH‐induced hypertension.Supported by Puente 28/2014 PUC
Adherence to the DASH Diet and Risk of Incident Chronic Kidney Disease: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Rebholz Casey , Crews Deidra , Grams Morgan , Levey Andrew , Miller Edgar , Appel Lawrence , Coresh Josef 
Published: June 2021

IntroductionThere are established guidelines for optimal dietary intake for the prevention of hypertension and cardiovascular disease. Evidence is lacking for effective dietary patterns for the prevention of chronic kidney disease (CKD).MethodsWe conducted prospective analyses of ARIC study participants without CKD at baseline (1987‐89, N=15,100). A score was created to assess adherence to the Dietary Approaches to Stop Hypertension (DASH) diet. Incident CKD was defined as an ICD‐9/10 code for a CKD‐related hospitalization or death, end‐stage renal disease, or decreased kidney function [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or 蠅25% eGFR decline from baseline] from baseline through 2011.ResultsThere were a total of 2,351 incident CKD cases during a median follow‐up of 21 years. Participants with a DASH diet adherence score in the lowest tertile were at an increased risk of CKD (Table). Of the individual components of the DASH diet adherence score, low intake of magnesium and calcium and high intake of sodium were strongly associated with increased risk of CKD.

Table. Risk of Incident Chronic Kidney Disease According to Tertile of DASH Diet Score

Low AdherenceTertile 1
Moderate AdherenceTertile 3
High AdherenceTertile 3
P‐value for trend

% (n)
‐‐
39% (6,017)
36% (5,500)
25% (3,911)
‐‐

IR (95% CI)
‐‐
9.29 (8.72, 9.90)
8.51 (7.95, 9.11)
8.48 (7.82, 9.19)
0.01

HR (95% CI)
Model 1
1.14 (1.02, 1.27)
1.02 (0.91, 1.13)
1 [Reference]
0.002

HR (95% CI)
Model 2
1.13 (1.01, 1.26)
1.01 (0.91, 1.13)
1 [Reference]
0.003

ConclusionsHigher adherence to the DASH diet may be associated with lower risk for developing CKD, independent of demographic characteristics, caloric intake, hypertension, diabetes, and kidney function. Further study is required to determine whether following a diet that is high in fruits, vegetables, and low‐fat dairy, and low in sodium, which has been shown to prevent hypertension and cardiovascular disease, might also prevent the development of CKD.
Additive Effects of Interpersonal Counseling and Mass Media on Psychosocial Determinants of Exclusive Breastfeeding among Vietnamese Mothers
Authors: Nguyen P , Kim S , Nguyen T , Hajeebhoy N , Tran L , Ruel M , Rawat R , Frongillo E , Menon P 
Published: June 2021

The pathways through which behavior change interventions impact breastfeeding (BF) practices have not been well studied. This study aimed to 1) examine separate and interactive effects of mass media (MM) and interpersonal counseling (IPC) on BF‐related psychosocial factors; and 2) assess the pathways through which intervention exposure affects exclusive breastfeeding (EBF). Survey data from mothers with children < 2 y (n=2045) from the process evaluation of Alive & Thrive's programs in Viet Nam were used. Exposure to MM only, IPC only, both, or neither was 51%, 5%, 19%, and 25%, respectively. Multiple linear regression showed consistent additive effects of MM+IPC on BF knowledge (b= 2.8, 11.5, and 14.4 for MM, IPC, and both, respectively), intention (b= 6.2, 14.9, and 18.0 for MM, IPC, and both), beliefs (b= 5.3, 12.7, and 16.8 for MM, IPC, and both), social norms (b= 5.0, 13.6, and 16.5 for MM, IPC, and both) and self‐efficacy (4.3, 14.6, and 17.4 for MM, IPC, and both). Women who viewed TV spots more frequently, recalled more messages, and those who received the recommended number of IPC visits had a higher score on psychosocial factors. Compared to no exposure, IPC and MM+IPC exposure were associated with 23.5% and 31.2% higher EBF, respectively. Structural equation modeling revealed that 90% of the total effect of IPC only or MM+IPC on EBF practice was explained by the psychosocial factors. The findings suggest that combining different behavior change modalities can lead to greater changes in psychosocial factors, which in turn positively affects breastfeeding behaviors.Funding: Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI360
Estimating the Sugars Content of Simulated Diets that Follow Eating Well with Canada's Food Guide
Authors: St‐Pierre Sylvie , Gilbert Jo‐Anne , Elvidge Lisa‐Anne 
Published: June 2021

Canada's Food Guide (CFG) recommends choosing foods lower in fat, sugar and salt and provides guidance to choose foods lower in added sugars. Added sugar levels in CFG's dietary patterns have never been estimated.ObjectivesEstimate the proportion of calories coming from added and free sugars in CFG's dietary patterns; and assess these results against the World Health Organisation (WHO) guidance on sugars.MethodsSugar‐containing foods were assigned to 3 categories: a) naturally occurring sugars source b) added sugars source or, c) free sugars source. Secondly, we simulated 8000 diets (500 for each age/sex group) consistent with CFG's dietary patterns and estimated their sugars content. Specifically, the grams of total sugars of a food having only naturally‐occurring sugars were all counted as naturally occurring sugars; the grams of total sugars of foods containing a mix of naturally occurring sugars and added or free sugars were all counted as added sugars and/or as free sugars. [This conservative methodology tends to overestimate added/ free sugar content.]ResultsMean percentage of energy (E) from total sugars was 21% (17‐24%). Added and free sugars estimates were respectively 3%E (1.7‐5.2%) and 7%E (4.5‐10%). Top contributors of sugars were from naturally occurring sources such as milk products, vegetables and fruits. An assessment of the nutrient distributions of the simulated diets against the Dietary Reference Intakes showed a low prevalence of nutrient inadequacy and an adequate energy level.ConclusionThese results showed that the sugar content of CFG dietary patterns is in line with the WHO sugar's recommendations. Adopting CFG's guidance leads to low levels of added/free sugars in the diets while meeting nutrient and energy requirements.
Development and Validation of a Novel Household Grocery Food Purchase Quality Score
Authors: Brewster Philip , Guenther Patricia , Jordan Kristine , Hurdle John 
Published: June 2021

Burdensome surveys and convenience sampling limit the ability to assess the quality of grocery food purchases. Our goal was to develop a metric for assessing such purchase data unobtrusively and at scale. We obtained de‐identified 2012 sales transaction data for 92,314 households in 4 geographic locations and re‐classified 1,888 higher‐order food descriptors into the 29 categories of USDA's Food Plan market baskets, which comply with the Dietary Guidelines. The standardized expenditure share for each category was the weighted average of all sex‐age groups used in the Food Plans. Quality of food purchases was evaluated by comparing the observed to the standardized expenditure share for each category. The 29 categories were then grouped into 10 food groups related to the Healthy Eating Index‐2010‐‐Total Vegetables, Greens and Beans, Total Fruit, Whole Fruit, Whole Grains, Dairy, Total Protein Foods, Seafood and Plant Proteins, Refined Grains, and Sweets‐‐and scored. Households who never purchased tobacco (n=71,475) had higher mean total scores (39.6 out of a possible 70) than those who did (36.3) (p<0.01) as well as higher scores for 8 of the 10 food groups (p<0.01). Thus, construct validity was established. This approach can be applied using longitudinal data to describe population‐level food purchase quality patterns and trends.Support: NIH grant T15‐LM007124; University of Utah Funding Incentive Seed Grant