bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P134: Peg-arginase 1 Limits Vascular Complications Of Type 2 Diabetes
Authors: Abdelrahman Ammar A , Bunch Katharine L , Rojas Modesto , Caldwell Ruth B , Caldwell Robert W
Published: May 2022

Background:
Distinct from its role in the urea cycle, the function of arginase 1 (A1) in regulating inflammatory responses has been demonstrated to be an intriguing target for controlling chronic, neuroinflammatory disease. Arginase competes with nitric oxide synthase (NOS) isoforms for their common substrate, L-arginine. Inflammatory cytokines increase expression of inducible NOS (iNOS) resulting in oxidant stress. Our group has recently shown that the polyethylene glycol-linked arginase 1 (PEG-A1) formulation, which provides enzyme stability, is a promising treatment that can counteract the destructive effects of neuro-inflammation and oxidative stress in ischemic retinal disease. This study assessed the efficacy of systemic PEG-A1 treatment in protecting the retinal neurovascular system from the effects of chronic hyperglycemia in a well-established murine model of type 2 diabetes.

Methods:
Studies were performed using 16-week-old obese, diabetic
db/db
mice to examine effects of chronic hyperglycemia and dyslipidemia on the retina. Lean
Db/db
littermates served as controls (n= 7/group). The
db/db
mice (n= 8/group) were treated with PEG-A1 (25 mg/kg IP) or PEG alone (control) 7 times over 2 weeks. Activation of the inflammasome pathway was examined by Western blots. Immuno-labeling of 4-HNE was used to quantify oxidative stress. Breakdown of the blood retinal barrier (BRB) was examined via albumin extravasation.

Results:
Expression of inflammasome pathway proteins, iNOS, caspase 1, IL-1β, and TNFα were upregulated in conjunction with increased cell death and breakdown of the BRB in
db/db
mice compared to controls. PEG-A1 treatment of the
db/db
mice significantly decreased the expression of iNOS, IL-1β, and TNFα, while reducing oxidative stress and preserving the BRB, as evidenced by decreased albumin leakage compared to
db/db
mice treated with PEG.

Conclusions:
Chronic diabetes increases retinal inflammation, oxidative stress and BRB disruption. We hypothesize that systemic PEG-A1 administration provides significant anti-inflammatory and anti-oxidant protection while inhibiting BRB breakdown in the
db/db
obese, diabetic mouse by decreasing L-arginine availability for iNOS and thereby inhibiting its expression/activity.
Abstract P139: Diet-induced Shifts In HDL Profiles Are Associated With Changes In Immune Parameters
Authors: Greco Julia , Palancia Esposito Christa , Mis Dominika , Andersen Catherine J
Published: May 2022

Introduction:
Preclinical and population-based studies have demonstrated immunomodulatory and anti-inflammatory properties of HDL; however, it is unclear whether diet-induced changes in HDL profiles can directly impact markers of immune inflammation.

Hypothesis:
We hypothesized that daily consumption of different egg-based diets, which have been shown to differentially impact serum lipids and lipoprotein profiles, would induce changes in HDL parameters that correspond to shifts in clinical and molecular immune markers.

Methods:
Healthy men and women (18-35y, BMI < 30kg/m
2
or < 30% body fat for men and < 40% body fat for women, n = 26) participated in a 16-week randomized, crossover intervention trial (NCT03577223), in which they consumed an egg-free diet for 4 weeks, followed by a 4-week diet containing either 3 whole eggs or 3 egg whites per day. Participants then followed a 4-week egg-free diet washout period, before switching to the alternative whole egg or egg white diet treatment. Fasting lipoprotein profiles, complete blood cell counts, and gene expression in peripheral blood mononuclear cells (PBMCs) was measured at the end of each diet period.

Results:
While no changes in total HDL particles, average HDL particle diameter, or the concentration of small (7.4-8.0 nm) or medium (8.1-9.5 nm) HDL particles was observed, the concentration of large HDL particles (10.8nm) was increased by whole egg intake as compared to intake of egg whites. A trend toward increased apolipoprotein A1 during the whole egg diet period as compared to the egg-free diet period was additionally observed. In line with our hypothesis, changes in large HDL concentrations between whole egg vs. egg white periods were inversely correlated with total white blood cell counts and absolute lymphocyte counts. CD8A mRNA expression in PBMCs was inversely correlated with concentrations of total and large HDL particles. Importantly, while serum choline and betaine were increased by whole egg intake compared to the other diet periods, no differences in pro-atherogenic and inflammatory trimethylamine-N-oxide (TMAO) between diet periods was observed.

Conclusion:
These findings suggest that diet-induced changes in HDL profiles are directly associated with changes in immune parameters.
Abstract P141: Downregulation Of Deletion Variants Of Telomerase Reverse Transcriptase (TERT) By Transforming Growth Factor-β1-silencing Decreases Mitochondrial ROS In Diabetic CD34
+
Cells
Authors: Jahan Jesmin , Montes de Oca Ildamaris , Maghrabi Ahmad , Lopez-Yang Christine , Beyer Andreas M , Garcia Charles , Jarajapu Yagna P
Published: May 2022

Telomerase reverse transcriptase (TERT) modulates mitochondrial levels of reactive oxygen species (mitoROS). Deletion variants, α-, β- and αβ, are negative regulators of TERT. Increased ROS levels in diabetic CD34
+
cells impair vasoreparative functions. Our recent studies showed that silencing of transforming growth factor-β1 (TGF-β1) decreased ROS levels and stimulated vasoreparative functions. This study tested the hypothesis that prevalence of TERT deletion variants is higher in diabetic CD34
+
cells and that TGF-β1-silencing decreases mitoROS by downregulation of the variants.

CD34
+
cells derived from either male or female nondiabetic (ND) (n=38) or diabetic (DB), both type 1 and type 2, (n=43) subjects were studied. Phosphorodiamidate morpholino oligomers (PMO) were used for TGF-β1-silencing. TERT variants were characterized by qPCR and agarose gel electrophoresis. MitoSOX-flow cytometry and ELISA were used for determining mitoROS levels and telomerase activity, respectively.

TGF-β1-silencing decreased mitoROS levels in DB-CD34+ cells (P<0.01 vs ND-cells, n=6). This effect was reversed by TERT inhibitor, BIBR1532 (1μM) (n=6) or mito-X-TERT, a decoy peptide that prevents mitochondrial translocation of TERT (n=5). TERT expression was higher in DB compared to ND cells (P<0.05, n=18) but telomerase activity was lower (P<0.05 vs ND, n=10). Prevalence of TERT deletion variants was higher among DB cells compared to ND (DB - 8/10 vs ND - 2/10 subjects have one or more of α, β, or αβ variants). TGF-β1-silencing downregulated the expression of TERT variants and increased full-length TERT that was accompanied by increased telomerase activity in DB-CD34+ cells (P<0.05 vs untreated, n=5).

This study suggests that diabetes is associated with higher prevalence of TERT variants that would impede mitochondrial functions of TERT. TGF-β1-silencing decreases mitoROS levels at least in part by downregulation of TERT variants.
Abstract P143: Arterial Stiffness And Body Mass In Young Adults: Another Aspect Of The Obesity Paradox?
Authors: Evsevyeva Maria , Eremin Michail , sergeeva oxana , ROSTOVTSEVA MARIA , Shchetinin Evgeny , Kudrjavtseva Victoria
Published: May 2022

Background:
The phenomenon of the" paradox " of obesity has been studied mainly in the elderly and even senile population in the presence of one or another obvious cardiovascular pathology, usually in combination with various complications. The study in this aspect of young people (YP), taking into account the surrogate endpoint in the form of vascular stiffness (VS), which is the basis for assessing vascular age, has not yet been conducted.

Aim:
to study VS in relation to metabolic status in YP with increase in body mass (BM), taking into account gender.

Methods:
93 boys and 171 girls aged 18 to 25 years were screened for risk factors (RF), including determination of total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG) and glucose. Angiological screening was performed using VaSera VS-1500 (Japan). VS type CAVI was evaluated on left (L) and right (R). Three groups were formed in accordance with criteria of reduced, normal and excessive BM.

Results:
With BM increase in these groups in YM, the TC was 3,5±0,2 3,5±0,1 4±0,2 (P2-3=0.038); LDL - 1,9±0,3 2,1±0,1 2,32±0,14; TG 1,1±0,3 1,04±0,1 1,6±0,2 (P2-3=0.020); HDL 1,02±0,08; 0,99±0,04; 0,95±0,06. The girls have TC 4,02±0,2, 3,94±0,08, 4,6±0,16( P2-3=0.003; P1-3=0.033); LDL 2,1±0,2, 2,21±0,08, 2,8±0,2 (P2-3=0.006; P1-3=0.011); TG 0,7±0,04, 0,82±0,04, 1,35±0,2 (P2-3=0.000; P1-3=0.006); HDL 1,5±0,08, 1,35±0,03, 1,13±0,13 (P1-2=0.028, P2-3=0.014, P1-3=0.013). Glucose increased slightly. Against background of BM growth with such negative shifts in metabolic parameters, the CAVI, on contrary, decreased. Its gender specificity was revealed - the difference between extreme weight categories for boys was 1.4 ( P1-3=0.000) for both CAVI sides, while for girls it was only 0.3 for CAVI-R (P1-3=0.091) and 0.4 for CAVI-L (P1-3=0.053).

Conclusion:
We revealed another obesity "paradox" in form of improvement in elastic vascular status with BM increase in YP. It is also paradoxical that VS improvement takes place despite obvious deterioration of metabolic RF. Obtained results should be used when conducting preventive interventions among YP in order to control not only traditional RF, but also VS state, as another important RF.
Abstract P160: Deficiency Of Angiotensin-converting Enzyme In Renal Proximal Convoluted Tubules Does Not Attenuate Atherosclerosis In Mice
Authors: Chen Hui , Masayoshi Kukida , Ye Dien , Howatt Deborah A , Moorleghen Jessica J , Sawada Hisashi , Daugherty Alan , Lu Hong S
Published: May 2022

Objective:
Angiotensin-converting enzyme (ACE) is the enzyme to generate Angiotensin II (AngII), an important contributor to atherosclerosis. ACE is present in all 3 segments (S1, S2, and S3) of proximal tubular cells (PTCs), and AngII concentrations are higher in kidney than in plasma. The purpose of this study was to determine whether ACE in PTCs contributes to atherosclerosis in mice.

Approach and Results:
Female ACE floxed mice and male Ndrg1-Cre ERT2
+/-
transgenic mice were bred to generate ACE f/f x Ndrg1-Cre ERT2
-/-
(PTC-ACE
+/+
) and ACE f/f x Ndrg1-Cre ERT2
+/-
(PTC-ACE
-/-
) littermates. Male PTC-ACE
+/+
(n=7) and PTC-ACE
-/-
(n=10) littermates in an LDL receptor -/- background were used for atherosclerosis study. After Cre genotyping using tail DNA, mice (both Cre ERT2
-/-
and Cre ERT2
+/-
) were injected with 150 mg/kg/day of tamoxifen for 5 consecutive days at the age of 4-6 weeks. Two weeks after the last injection of tamoxifen, mice were fed a Western diet (Envigo, Diet #TD.88137) for 12 weeks to induce hypercholesterolemia. Blood pressure was measured using a tail-cuff system. No difference of blood pressure was detected between the two genotypes (PTC-ACE
+/+
vs. PTC-ACE
-/-
: 126 ± 4 vs. 125 ± 3 mmHg; P = 0.763). All study mice were hypercholesterolemic, but plasma cholesterol concentrations were not different between the two genotypes (PTC-ACE
+/+
vs. PTC-ACE
-/-
: 1376 ± 119 vs. 1543 ± 93 mg/dl; P = 0.28). PTC-specific deletion of ACE was confirmed after termination using immunostaining of ACE. In mice with Ndrg1-Cre ERT2 transgene, immunostaining of ACE in kidney section showed an absence of ACE in S1 and S2 of PTCs, but ACE protein in S3 remained. Deletion of ACE in S1 and S2 of PTCs did not change hypercholesterolemia-induced atherosclerosis in the ascending and aortic arch regions (PTC-ACE
+/+
vs. PTC-ACE
-/-
: 9.6 ± 0.9% vs. 7.0 ± 1.9%; P = 0.13 by Mann-Whitney Rank Sum Test), as measured using an
en face
method.

Conclusion:
ACE deficiency in S1 and S2 of renal proximal tubular cells had no effect on atherosclerosis in hypercholesterolemic mice. Since ACE is more abundant in S3 than in S1 and S2 of PTCs, it would be important to determine the role of ACE in the S3 segment.
Abstract P163: Acute Treatment With Amyloid Beta Impaired Cerebral Artery Reactivity And Endothelial Sk Channel Activity
Authors: Xing Hang , Zhang Zhiqi , Feng Jun
Published: May 2022

Introduction:
The accumulation/aggregation of amyloid-beta(Aβ) has been recognized to play a key role in the progression of Alzheimer’s disease (AD) and the neurovascular dysfunction induced by Aβ may contribute to cognitive impairment and dementia during AD. Aβ deposition in cerebrovasculature exerts direct toxicity to smooth muscle cells and impairs nitric oxide signaling in the endothelium. Endothelium-dependent hyperpolarization and vascular relaxation are partially mediated by small-conductance calcium-activated potassium (SK) channels, and the inhibition of SK channels plays an important role in endothelial dysfunction. However, there has been limited investigation into the acute effect of Aβ on the endothelial SK channel function and related cerebrovascular reactivity.

Hypothesis:
We hypothesized that acute treatment with Aβ downregulates SK channel activity and impaired cerebrovascular reactivity.

Methods:
Aβ and SK channel activator NS309 were used in measuring
in-vitro
relaxation response of pre-contracted mouse cerebral arteries, and the SK channel currents of human cerebral artery endothelial cells by the whole-cell patch-clamp.

Results:
Mouse cerebral artery diameter was no significantly changed in incubation with Aβ (0.5-5μM) for 5 minutes (Fig. A, n=6, respectively). However, cerebral artery dilation with NS309 (10μM) was significantly decreased after incubation with Aβ (1μM) for 2 hours (Fig. B, n=6, respectively). The patch clamp recording showed that total potassium currents were no significantly changed in the incubation with Aβ (0.5-5μM) for 5 minutes (Fig. C&D, n=6, respectively). In contrast, the currents of SK channels in cerebral artery endothelial cells were significantly impaired after incubation with Aβ (1μM) for 2 hours (Fig. E&F, n=5-7, respectively).

Conclusions:
Acute treatment with Aβ dysregulated of cerebrovascular endothelial SK channels and impaired the cerebrovascular reactivity.
Abstract P165: Cardiac Capillary Pericytes Constriction Mediates Sleep Deprivation Induced Coronary Microcirculation Dysfunction
Authors: Wu Chao , Guo Ziyu , Tu Yimin , Wu Yaxin , Li Qing , Yu Xiaozhai , Li Yike , Yu Changan , Fu Yi , Gao Yanxiang , Kong Wei , Zheng jingang
Published: May 2022

Background:
Lack of sleep can lead to a variety of adverse cardiovascular events and even sudden death. In most cases, there is no obstructive coronary artery. Coronary microcirculation dysfunction (CMD) is thereby thought to play an important role in cardiovascular events caused by sleep loss. Pericytes regulate blood flow and mediate neurovascular signaling in brain. Here, we hypothesized that cardiac capillary pericytes mediate sleep loss related CMD.

Methods and Results:
Eight-week-old male C57BL/6J mice were deprived sleep for 6 hours or 72 hours. Cardiac function was detected by transthoracic echocardiography before and after sleep deprivation (SD). Vascular endothelial dyes were perfusion before tissue harvest to evaluate cardiac perfusion. By whole heart clearing, 3D immunolabeling and imaging, the effect of pericytes on cardiac capillary was accessed. Acute 6-hours total sleep deprivation or 72-hours severe sleep deprivation led to decreased cardiac systolic and diastolic dysfunction. Left ventricular end diastolic diameter and left ventricular end systolic diameter increased by 10.12% (0.32 mm of 3.14 mm) and 19.00% (0.31 mm of 1.63 mm). Although coronary flow velocity reserve showed no differences between sleep deprivation and control groups, the basal and maximum coronary blood velocity were increased in acute and severe total sleep deprivation mice, which illustrated CMD. Compared with mice in the control group, the area of cardiac perfusion in the sleep deprivation group was significantly reduced (33.42 ± 4.30% vs. 53.81 ± 7.42%,
P
< 0.05; SD group, n=7; control group, n=6). Whole mount heart imaging showed pericytes were widely distributed around the microvascular, without difference in regional distribution in the heart. In the area of cardiac perfusion defect, capillary blockages colocalized with pericytes, and the capillary diameter at the pericyte body was significantly reduced in sleep deprived mice (2.01 ± 0.12 μm vs. 2.92 ± 0.07 μm,
P
< 0.05; SD group, n=10; control group, n=10).

Conclusion:
Sleep restriction led to cardiac dysfunction and CMD, that pericytes mediated contraction of capillaries might contribute to the process. Cardiac pericytes would be a novel therapeutic target in sleep loss associated heart disease.
Abstract P167: Utilization Of A Novel Artery-on-a-chip For Target Discovery And Drug Testing In Experimental Vascular Medicine
Authors: Hummel Nora M , Paloschi Valentina , Glukha Nadiya , Maegdefessel Lars
Published: May 2022

The aorta-on-a-chip (AoOC) is a micro-engineered 3D in vitro model which aims to mimic the
in vivo
complexity of a human aorta in terms of cell-cell interaction, tissue architecture and hemodynamic conditions, i.e., the wall shear stress (WSS) force that the blood exerts on the vessel luminal surface in the direction of blood flow.The device used to generate the AoOC consists of a resealable glass chip with an intermediate semi-permeable membrane dividing the chip into two distinct chambers. This enables the flow of different fluids under varying dynamic conditions through the respective chambers. Primary aortic endothelial cells are cultivated on a thin layer of collagen on the flat-side of the membrane, whereas primary aortic smooth muscle cells are cultured on a fibronectin layer on the well-side of the same membrane. Once cells are confluent, the glass chip is assembled and sealed due to the slight pressure applied by the chip holder which is ultimately connected to a microfluidic pressure controller. The chamber containing the endothelial cells is subjected to a high flow rate of 1.2 ml/min, equivalent to 10 dynes/cm
2
, mimicking the shear stress of the aortic wall. In contrast, the smooth muscle cells are exposed to a slow flow rate of 20 μl/min, corresponding to 0.0042 dynes/cm
2
, that simulates the physiological diffusion rate between the intima and the media layer (of the aorta), ensuring an adequate supply of nutrients to the cells.The quality of the co-culture system is assessed by immunofluorescence staining using CD31 and SM22 antibody which specifically mark ECs and SMCs attached at opposite sides of the membrane. To evaluate transcriptomic changes under different flow conditions (static vs 10dyne/cm2) cells were carefully collected at opposite site of the membrane and subjected to RNA sequencing analysis.
Abstract P173: Collagen-iii, An Index Of Vascular Maintenance
Authors: Hoque Maruf M , Chappell John
Published: May 2022

Brain capillary integrity is compromised during stroke (Hu 2017). Re-establishing the blood-brain barrier (BBB) post-stroke requires integration of cues from endothelial cells (EC), pericytes (PC), and the extracellular matrix (ECM) to promote vessel remodeling. Two ECM components, Types III and IV Collagen (Col-III and Col-IV, respectively), support vascular growth and maintenance. Here, we utilized a murine embryonic stem cell (ESC) model to investigate how ECM mis-regulation impacts PC and EC collagen synthesis. ECM stability was targeted by administering α,α-dipyridyl (iron chelator) (Ikeda 1992) or Type IV Collagenase to ESC-derived vessels. Our aim was to establish potential mechanistic roles of both Col-III and Col-IV in promoting vascular maintenance. We observed by qRT-PCR that α,α-dipyridyl administration decreased Col3a1 expression, but not Col4a1, in a dose-dependent manner. Analysis by immunostaining and confocal microscopy revealed increases in vascular-associated and interstitial Col-IV with the lower doses of α,α-dipyridyl, but decreases in both Col-IV regions at higher doses. Preliminary imaging data for Col-III, however, suggested decreases in both vascular-associated and interstitial Col-III with lower doses, but increases in these Col-III regions with the highest α,α-dipyridyl dose. In separate experiments, Type IV Collagenase exposure reduced both vascular and interstitial Col-IV despite apparent increases in Col3a1 and Col4a1 gene expression. Taken together, these data suggest that perturbations to the ECM microenvironment surrounding developing blood vessels can elicit various compensatory responses depending on the severity and specificity of the ECM component targeted. These observations, support the idea that dynamic remodeling of the microvessel wall, and specifically the surrounding ECM, may contribute to microvascular instability, as seen in the BBB following acute ischemic stroke.
Abstract P175:
In Vitro
Cholesterol Treatment Does Not Reproduce Smooth Muscle Cell Phenotypic Plasticity Observed
In Vivo
Authors: Conklin Austin , Schlamp Florencia , Ord Tiit , Kaikkonen Minna U , Fisher Edward , Romanoski Casey E
Published: May 2022

Vascular Smooth Muscle Cells (SMCs) exhibit a significant degree of phenotypic plasticity in atherosclerotic lesions. Previously, this phenotypic plasticity, and specifically the re-differentiation of SMCs into macrophages, has been modeled in vitro using cholesterol treatment. We performed a meta-analysis of five different murine SMC lineage tracing single-cell RNA sequencing (scRNA-seq) experiments performed by four different research groups; we identified 24 different cell types and find considerable differences in the proportion of recovered normal ‘contractile’ SMCs and SMC-derived macrophages between experiments.

In addition, we performed bulk RNA-seq on cultured murine SMCs with and without cholesterol treatment for 0, 24, or 48 hours. We find that cholesterol treatment regulates transcripts associated with the induction of the unfolded protein response, reduction of cholesterol biosynthesis, and reduction in cell proliferation. Additionally, chromatin immunoprecipitation followed by high-throughput sequencing for H3K27ac performed on in vitro SMCs treated and untreated for 0, 24, or 48 hours reveals that AP-1 and ATF4 binding motifs are found more frequently at cholesterol treatment specific H3K27ac chromatin sites.

Finally, we compared transcriptomic data between in vivo vascular cell types identified in our meta-analysis and in vitro SMCs. We additionally included scRNA-seq data and microarray data collected for in vitro SMCs and bulk RNA-seq data collected for M1, M2, and oxLDL treated macrophages. We find that compared to the phenotypic plasticity observed in vivo, cholesterol exhibits modest effects on the transcriptomes of in vitro SMCs and does not reproduce the changes observed in vivo, while in vitro macrophages, especially oxLDL treated macrophages, more closely approximate their in vivo counterparts.

We conclude that differences between SMC lineage-tracing scRNA-seq experiments obscures the degree to which SMC-derived macrophages are present in murine atherosclerotic plaques, that cholesterol has modest effects on in vitro SMC transcriptomes, and that the effects of cholesterol do not reproduce the phenotypic plasticity observed in vivo.
Abstract P179: A Text Processing Tool To Identify And Characterize Carotid Artery Stenosis In Radiology Reports
Authors: Saadatagah Seyedmohammad , Elsekaily Omar , Alhalabi Lubna , Kullo Iftikhar J
Published: May 2022

Introduction:
We aimed to identify and characterize carotid artery stenosis (CAS), defined as ≥40% stenosis in the internal carotid artery (ICA) or the common carotid artery (CCA), among participants of the Mayo Vascular Disease Biorepository (VDB, n = 11,814).

Hypothesis:
A string-based text processing (TP) tool coded in R can analyze radiology text reports to ascertain and characterize CAS.

Methods:
After importing a radiology report into R, it was segmented for analysis and each segment was tested for 22 unique features. The TP tool was able to i) identify stenosis in the ICA or the CCA while excluding stenosis of vertebral arteries, subclavian arteries, or external carotid arteries, ii) recognize both quantitative and qualitative descriptions of CAS, iii) interpret numerical expressions by considering the surrounding text, iv) detect negations, and v) ascertain previous revascularization procedures if mentioned in the text. We manually ascertained CAS and characterized it in 800 randomly selected radiology reports to assess the performance of the TP tool in terms of precision, recall, and F-score.

Results:
We retrieved 21,651 imaging reports for 6,342 unique patients including 20,461 ultrasonography reports, 812 magnetic resonance imaging reports, 357 computed tomography scan reports, and 21interventional radiology reports. The performance of TP is outlined in
Table 1
.

Conclusion:
We demonstrate that a string-based TP tool coded in R is efficient and accurate in identifying and characterizing CAS from carotid radiology reports. The tool does not require natural language processing and could be used in a wide range of settings for genetic and biomarker studies.
Abstract P183: FFAR4: A Novel Target In Preventing Atherosclerosis?
Authors: Stuttgen Gage , Sahoo Daisy
Published: May 2022

Free fatty acid receptor 4 (FFAR4), also known as G-protein coupled receptor 120 (GPR120), is a long-chain unsaturated fatty acid receptor expressed in adipocytes, endothelial cells, and macrophages. Activation of FFAR4 helps maintain metabolic homeostasis by regulating adipogenesis, insulin sensitivity, and inflammation. While FFAR4 is best known for its role its role in preventing obesity and diabetes, recent studies have demonstrated that FFAR4 may also play an important role in the development of atherosclerosis and cardiovascular disease (CVD). Given FFAR4’s importance in anti-inflammatory signaling and high expression levels in macrophages, we designed experiments to test the hypothesis that FFAR4 prevents the development of atherosclerosis by reversing macrophage foam cell formation, a hallmark of early atherogenesis. In these studies, we isolated peritoneal macrophages from wild-type C57/Bl6 mice and incubated them with 20 μg/ml oxidized low-density lipoprotein (oxLDL) to generate foam cells. We then investigated the effects of FFAR4 activation on lipid accumulation, cytokine secretion, and cholesterol efflux. We found that activation of FFAR4 with synthetic agonist GW9508 reduced lipid accumulation as observed by decreased Oil Red O staining and reduced cellular cholesterol content. Activation of FFAR4 by GW9508 also decreased macrophage secretion of pro-inflammatory cytokines interleukin 1 beta (IL-1β) by 5.3-fold, interleukin 6 (IL-6) by 2.4-fold, monocyte chemoattractant protein-1 (MCP-1) by 44.1-fold, and tumor necrosis factor alpha (TNFα) by 2.4-fold. Additionally, activation of FFAR4 by GW9508 significantly increased [
3
H] cholesterol efflux to high-density lipoprotein (HDL) from peritoneal macrophages. Taken together, our results support an exciting and novel protective role for FFAR4 in the reversal of foam cell formation and could emerge this receptor as a new target for treating CVD by preventing accumulation of atherosclerotic plaque.
Implementation of an Appointment‐Based Cardiac Rehabilitation Approach: A Single‐Center Experience
Authors: Wright Catherine X. , Fournier Sean , Deng Yanhong , Meng Can , Hiller Susan , Oen‐Hsiao Joyce M. , Dreyer Rachel P.
Published: May 2022

Background

There has been a focus on alternative cardiac rehabilitation (CR) delivery models aimed at improving CR adherence and completion. We examined pre‐ and post‐CR health outcomes, reasons for discharge, and predictors of completion using a patient‐driven appointment‐based CR approach that uses center‐scheduled class start times.

Methods and Results

Data were used from an urban single‐center CR program at Yale New Haven Health (2012–2017) that enrolled 2135 patients. We evaluated pre‐ and post‐CR outcomes (12 weeks) using paired
t
tests and used a multivariable logistic regression model to examine predictors of CR completion (≥36 sessions) for the overall cardiovascular disease population. The mean age of participants was 65±12 years, 27.9% were women, and 5.1% were Black patients, and patients completed a median of 30 of 36 sessions. Patients achieved significant improvements in health outcomes, including across age and sex subgroups. The primary reason for discharge was completion of all 36 sessions of CR (46.4%). The final logistic regression model contained 12 predictors: age, sex, Black race, marital status, employment, number of physician‐reported risk factors, dietary fat intake >30%, obesity, lack of exercise, benign prostatic hyperplasia, and self‐reported stress and physical activity.

Conclusions

We demonstrated that patients participating in an appointment‐based CR program achieved significant improvements in health outcomes and across sex/age subgroups. In addition, older individuals were more likely to complete CR. An appointment‐based approach could be a viable alternative CR method to aid in optimizing the dose‐response benefit of CR for patients with cardiovascular disease.
Left Atrial Remodeling and Stroke in Patients With Sinus Rhythm and Normal Ejection Fraction: ARIC‐NCS
Authors: Bianco Francesco , De Caterina Raffaele , Chandra Alvin , Aquila Iolanda , Claggett Brian , Johansen Michelle C. , Gonçalves Alexandra , Norby Faye L. , Cogswell Rebecca , Soliman Elsayed Z. , Gottesman Rebecca , Mosley Thomas , Alonso Alvaro , Shah Amil , Solomon Scott D. , Chen Lin Yee
Published: May 2022

Background

Age‐related left atrial (LA) structural and functional abnormalities may be related to subclinical cerebral infarcts (SCIs) and stroke. We evaluated the association of 3‐dimensional echocardiographic LA contractility parameters with SCIs and stroke across the spectrum of tertiles of age increment in elderly patients with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation.

Methods and Results

We enrolled 407 participants (mean age, 76±8 years; 40% men) from ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study) undergoing a brain magnetic resonance imaging and 3‐dimensional echocardiographic examinations in 2011 to 2013. The sample was analyzed among age tertiles and subgroups: no cerebral magnetic resonance imaging–detectable infarcts (n=315), magnetic resonance imaging–diagnosed SCIs (n=58), and clinically diagnosed stroke (n=34). The frequency of SCIs significantly increased over age tertiles (
P
trend 0.023). LA global longitudinal strain—a 3‐dimensional echocardiographic index of LA reservoir function—and E/e’ divided by LA global longitudinal strain—an index of LA stiffness—worsened across age tertiles (
P
trend 0.014 and 0.001, respectively), and only in the categories of SCIs (
P
trend <0.001 and 0.045, respectively) and stroke (
P
trend 0.001 and 0.011, respectively). LA global longitudinal strain was negatively associated with increased odds of SCIs (
P
=0.036,
P
=0.008, and
P
=0.001, respectively) and strokes (
P
=0.043,
P
=0.015, and
P
=0.001, respectively) over age tertiles, with a significant interaction between age tertiles (interaction
P
=0.043 and
P
=0.010, respectively). E/e’ divided by LA global longitudinal strain was positively associated with the presence of SCIs (
P
=0.037,
P
=0.007, and
P
=0.001, respectively) and strokes (
P
=0.045,
P
=0.007, and
P
=0.003, respectively) over age tertiles, with a significant interaction only for SCIs (interaction
P
=0.040) and not for clinical stroke.

Conclusions

In a large cohort study of elderly patients, among participants with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation, measures of worse age‐related LA reservoir function and stiffness are associated with higher odds of SCIs and stroke.
A new, narrowly endemic species of swamp-dwelling dusky salamander (Plethodontidae: Desmognathus) from the Gulf Coastal Plain of Mississippi and Alabama
Authors: PYRON R. ALEXANDER , O’CONNELL KYLE A. , LAMB JENNIFER Y. , BEAMER DAVID A.
Published: May 2022

We describe a new, narrowly endemic species of swamp-dwelling dusky salamander (Plethodontidae: Desmognathus pascagoula sp. nov.) from the Gulf Coastal Plain of southeastern Mississippi and southwestern Alabama based on linear morphometrics, mitochondrial DNA, and single nucleotide polymorphisms from 881 loci produced using genotype-by-sequencing. Some populations of the new species were historically referred to as D. auriculatus, a polyphyletic assemblage of at least three species in the Atlantic and Gulf Coastal Plain from Texas to North Carolina. Populations of D. auriculatus from the Gulf Coastal Plain in Louisiana and Mississippi were recently described as D. valentinei. The new species includes populations that were tentatively referred to D. valentinei, but we find it is morphologically, genetically, and geographically distinct. It is smaller, has a more defined dorsal color pattern, more irregular whitish “portholes” in up to three rows on the lateral surfaces of the body and tail, and a brighter orange or yellowish orange postocular stripe. At present, the new species is known from only six extant populations in the lower Pascagoula, Escatawpa, and Mobile drainages. The latter represents a distinct phylogeographic lineage. We also refer a historical collection from the northeastern side of the Mobile-Tensaw River Delta to this species, suggesting a much broader range in the past. We suspect that more populations remain to be discovered in the area, and their potential species-level distinctiveness should be tested further. This discovery increases knowledge of the biodiversity in the southeastern United States Coastal Plain, a candidate region meeting the global criteria for a “biodiversity hotspot,” and underscores the amount of cryptic diversity likely remaining to be discovered and described in Nearctic salamanders.
Expanding the taxonomic knowledge of Adelosgryllus Mesa & Zefa, 2004 (Orthoptera: Grylloidea: Phalangopsidae): description of four new species for Brazilian subterranean habitats
Authors: MERLO RAYANNE LAYS SANT’ANA , CASTRO-SOUZA RODRIGO ANTÔNIO , JUNTA VITOR GABRIEL PEREIRA , FERREIRA RODRIGO LOPES
Published: May 2022

In this study, four new Brazilian species are described for the genus Adelosgryllus Mesa & Zefa, 2004, occurring in Minas Gerais, Tocantins and Pará states. Three of these species were found in caves and one was found in endogenous habitats, representing the first record of species form this genus for such habitats. The morphology of the phallic complex was used as the main criterion for distinguishing the new species, the copulatory papilla was also described for one of the new species. Finally, we bring a brief discussion about the ecology, distribution, and conservation of these species.
Testing the Feature Alignment Technique (FAT) in an Ensemble-Based Data Assimilation and Forecast System with Multiple-Storm Scenarios
Authors: Stratman Derek R. , Potvin Corey K.
Published: May 2022

Storm displacement errors can arise from a number of potential sources of error within a data assimilation (DA) and forecast system. Conversely, storm displacement errors can cause issues for storm-scale, ensemble-based systems using an ensemble Kalman filter (EnKF), such as NSSL’s Warn-on-Forecast System (WoFS). A previous study developed a fully grid-based feature alignment technique (FAT) to mitigate these phase errors and their impacts. However, that study developed and tested the FAT for single-storm cases. This study advances that work by implementing an object-based merging and matching technique into the FAT and tests the updated FAT in more complex scenarios of multiple storms. Ensemble-based experiments are conducted with and without the FAT for each of the scenarios. The experiments’ analyses and forecasts of storm-related fields are then evaluated using subjective and objective methods. Results from these idealized multiple-storm experiments continue to reveal the potential benefits of correcting storm displacement errors. For example, running the FAT even once can mitigate the “spinup” period experienced by the no-FAT experiments. The new results also show that running the FAT prior to every DA cycling step generally leads to more skillful forecasts at the smaller scales, especially in earlier-initialized forecasts. However, repeatedly running the FAT prior to every DA step can eventually lead to deterioration in analyses and forecasts. Potential solutions to this problem include using longer cycling intervals and running the FAT prior to DA less often. Additional ways to improve the FAT along with other results are presented and discussed.

Significance Statement

The purpose of this work is to explore the impact of correcting storm displacements on analyses and forecasts of storms using an ensemble-based data assimilation and forecast system in an idealized framework. Storm displacement errors are a common problem in current operational and experimental storm-scale forecast systems, so understanding their impact on these systems and providing a method to help mitigate them is important. Results from this study indicate that correcting storm displacement errors with the feature alignment technique can greatly improve analyses and forecasts in multiple-storm scenarios. Future work will focus on exploring the impact of correcting storm displacement errors in a real-data, storm-scale data assimilation and forecast system.
CRP Albumin Ratio May Predict No Reflow in Patients Undergoing Percutaneous Coronary Intervention for Saphenous Vein Graft Stenosis
Authors: KANAL Yücel , Şeyda KANAL Hatice Eftal , YAKUT İdris , ÖZEN Yasin , ÖZBAY Mustafa Bilal , Gülcihan BALCI Kevser , YAYLA Cagri
Published: May 2022

Many hypotheses have been proposed to explain no-reflow (NR). Some of these hypotheses, state that NR may be caused by damage to the vascular endothelium and an inflammatory process. In a recent study that did not include patients with coronary artery bypass graft (CABG), the ratio of C-reactive protein (CRP) to albumin (CAR) was found to be associated with NR. Our study aims to evaluate the relationship between CAR and NR in patients who underwent percutaneous coronary intervention (PCI) for saphenous vein graft (SVG). In this retrospective study, among the patients with CABG who underwent primary or elective coronary angiography, 242 patients who underwent PCI to the SVG were selected. The incidence of NR was 19.8% (n = 48). Diabetes mellitus, left ventricular ejection fraction (LVEF), stent length, and CAR were found as independent predictors of NR in multivariate logistic regression analysis (P < .05). Using a cut-off level of .930, the CAR predicted NR with a sensitivity of 75% and a specificity of 73% (AUC: .814, 95% CI: .749–.879, P < .001). The CAR was a better predictor than both stent length and LVEF. CAR was found to be the strongest predictor of NR in our study.
Rapid diagnostic strategies using high sensitivity troponin assays: what is the evidence and how should they be implemented?
Authors: Collinson Paul , Dakshi Ahmed , Khand Aleem
Published: May 2022

The introduction of high sensitivity measurement of cardiac troponin T (hs cTnT) and cardiac troponin I (hs cTnI) has given the laboratory the ability to measure very low levels of cardiac troponin. The limit of detection of these assays is well below the 99th percentile. These low levels can also be measured with small values of imprecision. A range of algorithms combining presentation measurement with repeat sample intervals of as little as one to 2 hours have been developed. These are able to predict with acceptable accuracy the diagnosis that would be achieved with continued repeat sampling out to six to 12 hours from presentation. In this article, we review the evidence for the diagnostic accuracy of these approaches and the practical aspects of implementation into routine clinical practice.
Understanding German Consumers’ Intention to Adopt COVID-19 Infection Prevention Measures: A Moral Decoupling Perspective
Authors: Böhm Rebekka A. , Orth Ulrich R.
Published: May 2022

Getting consumers to adopt infection prevention measures is important for society to overcome the coronavirus pandemic. This research adopts a moral decoupling perspective to examine how consumers in Germany respond to perceived transgressions of COVID-19 infection prevention regulations. Focusing on two nonpharmaceutical measures (mask wearing, social distancing) as well as a pharmaceutical one (vaccination), two empirical studies indicate that transgression relevance influences intention to adopt the measure (in parallel) through judgment of performance and judgment of morality. Type of transgression moderates the effect of transgression relevance on morality, but not on performance. In addition, effects weaken as a person’s fear of infection increases. Effects are robust, though, when controlling for moral decoupling and moral delegation (Study 1), and additionally for psychological reactance and political orientation (Study 2). Implications for research and practice evolve around new insights into how to get consumers to adopt infection prevention measures more effectively.
Supervisees’ Nondisclosure in South Korea and the United States: A Cross-Cultural Comparison
Authors: Son Eunjung , Ellis Michael V. , Hutman Heidi
Published: May 2022

This study investigated the effects of supervisee characteristics (rejection attachment), the supervisory relationship (supervisory working alliance, role conflict), and Asian cultural values on supervisee nondisclosure (clinically related and supervision related nondisclosures) for South Korean and U.S. American supervisees. Participants were 474 predominantly female supervisees in counseling and clinical psychology programs (227 South Korean, 247 U.S. American). Three major findings emerged: (a) the four predictors collectively predicted both types of supervisee nondisclosure jointly in both countries, (b) the supervisory working alliance predicted the two types of supervisee nondisclosure jointly in both countries, and (c) post hoc tests suggested that the supervisory working alliance mediated the relations of role conflict and rejection attachment with supervisee nondisclosure in both countries, and the relation of Asian cultural values with supervisee nondisclosure for South Korean supervisees. Implications for theory, research, and practice are discussed.
Sexual identity and Fascist space in Milena Milani's Storia di Anna Drei
Authors: Salsini Laura A
Published: May 2022

Milena Milani's 1947 novel Storia di Anna Drei serves as an analysis of Fascist ideology regarding women. In the text, the protagonist pushes back against the regime's oppressive attitudes, allowing for an exploration of female sexuality and authenticity. Milani sets this critique against the backdrop of both pastoral and urban landscapes, demonstrating how the physical world can become a gendered space. In doing so, she significantly expands the cultural debate during the ventennio on the comparative merits of the countryside versus the modern city. The regime promulgated competing narratives about these sites, narratives that Milani challenges as she demonstrates how both spaces can prove harmful to women.
Local government’s response to dissatisfaction with centralized policies: the “do-it-yourself” approach
Authors: Uster Anna , Cohen Nissim
Published: May 2022

The literature on intergovernmental relationships discusses the tension between centralization and local autonomy. However, few studies question local authorities’ response when dissatisfied with central government policies. Using Hirschman's model of exit, voice and loyalty, we explore local government's response to such dissatisfaction. Specifically, we suggest that local authorities may adopt a “do-it-yourself” approach, unilaterally engaging in semi-legal strategies to improve outcomes. This solves immediate local organizational problems, without waiting for approval. Using the Israeli case, we show how a pervasive culture of “do-it-yourself” affects local governments’ responses. We also discuss implications for the relationship between the two bodies.

Points for practitioners

Our findings shed light on local–central government relations, emphasizing the do-it-yourself approach. While this approach could strengthen political participation, increasing local government's involvement in public policy, it also enables local players to use semi-legal behaviors. Central government decision-makers might prevent these behaviors, strengthening administrative institutions’ enforce, regulatory enforcement and enhancing local autonomous political culture, transparency and integrity. By contrast, continuing to maintain weak formal institutions encourages the appearance of strong informal institutions.
Compassion fatigue among social workers in juvenile offender systems in Chile
Authors: Reyes-Quilodran Claudia , Ruffolo Mary C , Chang Shih-Ya
Published: May 2022

In the past few decades, both the local and international press have addressed flaws within the juvenile justice systems in Chile. However, very few studies have examined the support provided to social workers working in this field. This article, using exploratory survey research methods, explores the perspective of social workers about how these systems support their well-being and overall work functioning. The survey uses a snowball sampling technique to reach social workers who work in nonprofit organizations serving juvenile offenders in the metropolitan region in Chile. The results show that social workers are experiencing moderate levels of compassion fatigue. Different issues emerged centered on a lack of organizational support related to teamwork, training, and pay.
Reducing the Use of Segregation for People with Serious Mental Illness
Authors: Maszak-Prato Serena , Graham Leigh
Published: May 2022

This study, using data from a state correctional agency, examines the use of segregation for people with serious mental illness in prisons. Our investigation shows deviations from departmental policy regarding the housing of individuals with serious mental illness (SMI); frequent use of segregation as a response to self-harm episodes and suicide attempts; and that people determined to be most impaired by a serious mental illness were typically placed in segregation. These findings suggest that correctional staff need to decouple disciplinary actions and responses from mental health symptoms, and avoid a punitive approach to incidents of self-harm or suicidality.
Entropy and stability analysis on blood flow with nanoparticles through a stenosed artery having permeable walls
Authors: Shahzad Muhammad Hasnain , Awan Aziz Ullah , Akhtar Salman , Nadeem Sohail
Published: May 2022

In this research, the electro-osmotic effects are highlighted for a blood-based hybrid nanofluid flow across an artery infected with multiple stenosis. The artery has permeable walls together with slip boundary effects. The slip and permeable boundary conditions model the more realistic blood flow problems. The governing equations of the problem are converted into non-dimensional form by introducing adequate dimensionless variables and acquired the exact solutions. The detailed study of heat transfer is given by Joule heating and viscous dissipation effects. The disorder of fluid flow is investigated by the mathematical study of entropy generation. Analytically attained solutions are examined graphically for both symmetric and non-symmetric shapes of stenosis. Streamlines are analyzed for varying values of flow rate Q and electro-osmotic parameter m. The flow velocity has smallest values on the axis of channel and gets higher value near the boundary walls. The temperature profile delineates opposite behavior to the velocity, and it is parabolic in nature. The velocity reduces towards the non-uniform stenosis except for electroosmotic parameter m. The temperature has larger magnitude in the case of anti-symmetric stenosis. Moreover, the stability of velocity solution is also analyzed.