bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P323: Direct Vascular Endothelial Actions Of Angiotensin II Via At
1
R And No Signaling Revealed By Intravital Multiphoton Microscopy.
Authors: Shroff Urvi Nikhil , Deepak Sachin , Izuhara Audrey , Peti-Peterdi Janos , Gyarmati Georgina
Published: September 2022

The renin-angiotensin system (RAS) controls blood pressure and body fluid balance. The classic vasoactive effects of RAS are mediated by the binding of angiotensin II (ANGII) to ANGII type 1 receptors (AT
1
R) in vascular smooth muscle cells leading to vasoconstriction, or to opposing ANGII type 2 receptors (AT
2
R). However, only few studies investigated the direct effects of ANGII on vascular endothelial cells (VEC) in vivo and the mechanisms how VECs may mitigate ANGII-mediated vasoconstriction. The present study aimed to explore the molecular mechanisms and pathophysiological relevance of the direct actions of ANGII on VEC in the kidney. VEC calcium dynamics and NO synthesis were visualized by using intravital multiphoton microscopy (MPM) of Cdh5-G6 mice that selectively express the ratiometric Ca
2+
reporter GCaMP6f/tdTomato in VECs, or the endothelial uptake of iv injected nitric oxide (NO) sensitive dye DAF-FM, respectively. Bolus injection of ANGII (400 ng/kg, ia.) triggered a >4-fold increase in VEC calcium in afferent (AA) arterioles and glomerular capillaries, but not in peritubular capillaries. These responses were blocked by pretreatment with the AT
1
R inhibitor Losartan (60mg/kg ip.), but not by the AT
2
R inhibitor PD123319 (25mg/kg ip.)(1.2+/-0.4 p<0.001 and 5.6+/-0.9-fold, p=0.3, respectively). VEC responded to acute ANGII by increased NO synthesis as indicated by >1.5-fold increase in DAF-FM fluorescence intensity as compared to baseline (p<0.0001). In mice with unilateral ureteral obstruction (UUO), a well-known high ANGII and vasoconstrictor state associated with endothelial dysfunction, the ANGII induced calcium increase in VECs was significantly reduced (2.8+/-0.3-fold) as compared to control (4.6+/-0.4-fold, p<0.01). These results correlated with the significantly reduced AA diameter in UUO compared to control (8.2+/-0.4 and 10.43+/-0.3 μm, respectively, p<0.001). In summary, ANGII has major direct effects on VECs NO production that counterbalances agonist-induced vasoconstriction. These effects are diminished in conditions with endothelial dysfunction leading to increased vascular contractility. Cell-specific targeting of ANGII actions may represent exciting future therapeutic opportunities.
Abstract P325: Visit-To-Visit Blood Pressure Variability Is A Major Risk Factor For Renal Outcomes In Hypertensive Patients: Evidence From The 20-Year Follow-Up Of The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
Authors: Rostamian Somayeh , Godec Thomas , Gupta Ajay K , Whiteley William , Mackay Judith , Whitehouse Andrew , Sever Peter
Published: September 2022

Introduction:
Observational studies showed that visit-to-visit blood pressure variability (BPV) is a significant independent risk factor for cardiovascular morbidity and all-cause mortality. However, the relation between BPV with renal outcomes remains controversial.

Methods:
In the ASCOT-Legacy Study, 7,092 hypertensive patients, aged 40-79 years, who had at least three other cardiovascular risk factors have been followed for up to 20 years to report the long-term determinants of renal outcomes. All available BP visit records (n=100,933) were included after excluding the first six months observations. The mean of systolic blood pressure (SBP) as a measure of BP control and the standard deviation (SD) of all SBPs as an estimate of visit-to-visit BPV were calculated for the five years of the trial. Participants were then followed for up to 15 years after the end of the trial using the UK National Health Service (NHS) electronic health records. Total renal outcomes (renal failure, chronic kidney disease, dialysis and transplantation) were measured using Cox proportional hazards model.

Results:
About one-third (n=2,354) of participants experienced at least one of the renal outcomes during the follow-up. Our findings showed that an increase per one SD (10.39 mmHg) in mean SBP was associated with a hazard ratio (HR) of 1.23 (95%CI 1.17-1.29; p<0.001) and an increase per one SD (4.72 mmHg) in BPV was associated with an HR of 1.20 (95%CI 1.14-1.26; p<0.001) for total renal outcomes. Likewise, BPV was associated with a higher risk of renal failure (1.19 [95%CI 1.13-1.26]; p<0.001), chronic kidney disease (1.25 [95%CI 1.08-1.44]; p=0.002), and dialysis and transplantation (1.43 [95%CI 1.19-1.71]; p<0.001) after adjusting for mean BP, number of visits and other confounding variables.

Conclusions:
Both mean SBP and BPV are strong predictors of long-term renal outcomes, but BPV, independent of mean BP, confers a significant additional risk and should be considered for future preventive and therapeutic strategies.
Abstract P326: Trimethylamine, A Gut Bacteria Metabolite And Air Pollutant, Increases Blood Pressure, Proteinuria And Markers Of Kidney Damage In Rats.
Authors: Ufnal Marcin , Maksymiuk Klaudia , Szudzik Mateusz , Chabowski Dawid
Published: September 2022

Trimethylamine oxide (TMAO) is a biomarker in cardiovascular and renal diseases. TMAO originates from the oxidation of trimethylamine (TMA), a product of gut microbiota and industry-derived pollutant, by flavin monooxygenases (FMOs). The effect of chronic exposure to TMA on cardiovascular and renal systems is undetermined. Metabolic, hemodynamic, echocardiographic, biochemical and histopathological evaluations were performed in male, 12-week-old rats receiving water (control group) or TMA (500 μM/day) in water for 18 weeks (each group: n=9). TMA and TMAO levels, the expression of FMOs and RAS genes were evaluated in various tissues. Data are expressed as the median (Q1; Q3) or mean ± SE. In comparison to controls, rats receiving TMA had significantly increased systolic blood pressure (mmHg; 151.2 ± 7.0 vs. 126.3 ± 3.8; P<0.05), urine protein to creatinine ratio [3.4 (3.3; 4.2) vs. 1.6 (1.5; 2.8); P<0.05], urine KIM-1 levels (pg/ml; 3 519.0 ± 301.6 vs. 2 338.3 ± 244.0; P<0.05), mild degeneration of renal bodies with glomerulosclerosis, and hypertrophy of the tunica media of arteries and arterioles. There was no significant difference between the groups in body weight, water-electrolyte balance and echocardiographic parameters and RAS expression. TMA group had marginally increased 24hr TMA urine excretion [μM; 5.0 (3.8; 5.5) vs. 0.3 (0.2; 0.4); P<0.01]. However, TMA serum level [μM/l; 0.32 (0.27; 0.64) vs. 0.04 (0.03; 0.04)], TMAO serum level [49.5 (45.8; 84.8) vs. 9.0 (6.5; 11.9)] and 24hr TMAO urine excretion [255.4 (237.2; 311.1) vs. 10.6 (10.3; 11.2); all P<0.001] were increased. TMA group had lower FMOs expression in the kidneys but significantly increased TMAO levels in the liver [μM/kg; 35.9 (29.3; 41.9) vs. 5.4 (4.2; 9.6)], renal cortex [189.7 (82.2; 204.5) vs. 14.5 (13.1; 21.9)], renal medulla [192.0 (74.0; 213.7) vs. 18.5 (14.4; 27.8)] and heart [96.3 (90.3; 112.4) vs. 3.2 (2.4; 5.8); all P<0.001]. In conclusion, chronic exposure to TMA increases blood pressure and increases markers of kidney damage including proteinuria and KIM-1. TMA is rapidly oxidized to TMAO in rats, which may limit toxic effects of TMA.
Abstract P335: Contribution Of The Gut To The Salt-sensitive Phenotype Of Dahl S Rats Is Reflected In Increased Sodium Absorption In The Distal Colon
Authors: Keith Caullin B , Bearss Nicole , Joe Bina , Zubcevic Jasenka A
Published: September 2022

Salt-sensitive hypertension in Dahl sensitive (Dahl S) rats is primarily attributed to sodium mishandling associated with kidney dysfunction, and very few studies interrogated sodium absorption in the gut of Dahl S rats and its potential contribution to the salt-sensitive phenotype. To assess this, we compared sodium channel (ENaC)-driven sodium (Na
+
) currents, as a measure of Na
+
transport across the distal colon, the primary sodium absorption site in the GI tract, between Dahl S and Dahl salt-resistant (Dahl R) rats
ex vivo
. In parallel, we evaluated fecal sodium levels to assess overall fecal sodium loss in Dahl S and R rats. Male adult (12-14wo) Dahl S and R were administered a low sodium diet (0.3% NaCl, Teklad)
ad libitum
from weaning. Prior to the experiment, food intake/rat was measured every day for three consecutive days. On the day of experiment, rats were euthanized by an overdose of isoflurane. Distal colons were dissected and transferred to the Ussing chamber with oxygenated warm Krebs solution containing d-glucose. Increasing concentrations of the ENaC blocker amiloride (0.01-1000uM) were applied to the Ussing chamber on the apical side of the distal colon in 10-minute intervals. Maximum decreases in total ionic current across the distal colon were measured in real time following addition of amiloride to quantify ENaC Na
+
current across the distal colon. Fecal samples were homogenized in distilled water, and sodium levels per gram of fecal mass were determined by flame photometry. Despite no differences in food intake, we observed a dose-dependent 2 to 4-fold higher responses to amiloride in the distal colon of Dahl S compared to Dahl R rats, suggesting elevated Na
+
current in the Dahl S. Conversely, a ~2-fold lower Na
+
concentration was detected in the feces of Dahl S compared to Dahl R rats. In conclusion, elevated ENaC-driven Na
+
current in the distal colon, coupled with reduced fecal Na
+
concentration, suggest higher absorption/transport of Na
+
across the distal colon of Dahl S compared to Dahl R rats, which was independent of salt intake. Considering that the circulating Na
+
levels are reportedly maintained in the Dahl S by the overworked kidney, elevated colonic sodium absorption may contribute to kidney disease and salt-sensitive phenotype in Dahl S.
Abstract P339: A Possible Role Of Neuronal Adam17 In The Development Of Hypertension And Related Cognitive Impairment By Altering The Microenvironment
Authors: Wang Jiawei , Yuan Shenglan , Wu Hanxue , Xu Jiaxi
Published: September 2022

Hypertension is one of the most prevalent cardiovascular diseases worldwide and is known to be dominated by the sympathetic nervous system (SNS). Previously, we found that targeting A Disintegrin and Metalloproteinase 17 (ADAM17) in glutamatergic neurons was able to blunt Ang-II-induced excitation of pre-autonomic neurons, and blocked DOCA-salt treatment-induced sympatho-excitation in mice, thereby alleviating their development of hypertension. However, how ADAM17 support the activation of pre-autonomic neurons remains unknown. Beyond the glutamatergic neurons, we found in the current study that microglial activation and increase of pro-inflammatory cytokine levels in the hypothalamus, induced by DOCA-salt treatment, were blunted in those mice with ADAM17 knockout in glutamatergic neurons (A17G; number of CD11b+cells per line: NT+DOCA
vs.
A17G+DOCA= 11±2
vs.
6±1,
P=
0.0017; normalized TNFα level: NT+DOCA
vs.
A17G+DOCA= 1.00±0.37
vs.
0.67±0.11,
P<
0.05; normalized IL-6 level: 1.00±0.32
vs.
0.59±0.20,
P<
0.05). Especially, it also reversed DOCA-salt-induced downregulation of Gad67 mRNA expression (NT= 1.00±0.11, NT+DOCA= 0.66±0.12, A17G= 1.02±0.15, A17G+DOCA= 1.67±0.24 fold of change, NT
vs.
NT+DOCA and A17G
vs.
A17G+DOCA:
P<
0.05), and normalized the decreased level of GABA in hypothalamus (normalized GABA levels: NT= 1.00±0.15, NT+DOCA= 0.84±0.09, A17G+DOCA= 1.09±0.17, NT
vs.
NT+DOCA:
P<
0.05), suggesting that in addition to the effect of ADAM17 on the neuron itself, it might also regulate the SNS through altering the neuronal microenvironment. In L-NAME hypertensive model, though A17G mice showed no improvement in NOS-blockade-induced dysfunction of neuro-vascular coupling (increase of CBF induced by whisker-stimulation: NT
vs.
A17G= 24.34±11.20
vs.
24.87±15.78 PU%), it did exhibit improved performance in Barnes maze test (latency time: NT
vs.
A17G= 32.77±19.36
vs.
95.54±59.03 s,
P=
0.002), suggesting that ADAM17 in glutamatergic is critical for the process of neuronal damage induced by hypoxia and ischemia, possibly through modulating the homeostasis of neuronal microenvironment.
Abstract P351: Prognosis Of Different Forms Of Resistant Hypertension
Authors: De La Sierra Alejandro , Ruilope Luis M , Vinyoles Ernest , Gorostidi Manuel , Segura Julian , Williams Bryan
Published: September 2022

Resistant hypertension (RH) is related to increased risk for cardiovascular events. We aimed to evaluate the risk of total and cardiovascular mortality associated with RH in comparison to controlled hypertension, as well as in true versus “white-coat” RH. From the mortality data of the Spanish ABPM Registry, including 35119 treated patients, we identified 9408 RH, defined as office BP ≥ 140/90 mmHg while treated with ≥ 3 drugs (8577 patients), or treated and controlled (office BP < 140/90 mmHg) with ≥ 4 drugs (831 patients). They were compared against 8144 patients treated with ≤ 3 drugs and having normal office BP. In addition, among 8577 patients with uncontrolled RH, 5288 (61.7%) had true RH (24-h BP ≥ 130/80 mmHg) and 3289 (38.3%) had “white coat” RH (24-h BP < 130/80 mmHg). Median follow-up was 5 years. Total and cardiovascular mortality were assessed through death certificates. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated through Cox-proportional models, adjusted for age and sex. Table shows the number of patients in each group, number of total and cardiovascular deaths and HR of the 2 comparisons performed. Compared to treated and controlled patients, those with RH had and increased risk of total (19%) and cardiovascular (32%) mortality. Likewise, true RH had an increased risk of total (42%) and cardiovascular (81%) mortality, in comparison with “white-coat” RH. We conclude that RH is associated with and increased total and cardiovascular mortality. In RH patients with elevated office BP, the concomitant elevation of 24-hBP (true RH) is also associated with an increased risk of mortality when compared with those with normal 24-h BP (“white-coat” RH).
Abstract P352: Rates Of Diagnostic Work-up By Magnetic Resonance Imaging Of The Abdomen For Patients With Resistant Hypertension
Authors: Luo Xiao Ran , Funes Hernandez Mario , Isom Robert , Bhalla Vivek
Published: September 2022

Resistant hypertension affects 8.9% to 33% of all persons with hypertension, and is associated with higher risks of death, major cardiovascular events, left ventricular hypertrophy, progressive kidney disease, and cognitive impairment. Guidelines recommend diagnostic work-up for resistant hypertension including assessment of the renal vasculature but rates of diagnostic studies in real-world practice are not well known. From a cohort of patients with resistant hypertension (n = 4660) from 2008-2016 prior to the founding of the Stanford Hypertension Center, we quantified assessment of renovascular disease. We observed that 2.5% (n = 118) of the patients had an abdominal magnetic resonance imaging (MR abdomen) performed, and were of ages 45-92, 61% male and 39% female. Although all 118 of these patients had an MR abdomen after their index date of resistant hypertension (their most recent MR abdomen was taken an average of 7.4 years after their index date), only 36% (n = 43) of these 118 patients had imaging reports that described the renal arteries in the body or the conclusion of the report. Of these 43 patients, 7% (n=3) had MR records describing renal artery stenosis. In comparison, 100% (n = 263) of kidney donors who had had an MR abdomen performed during the same interval (2017-2021) had imaging reports that described their renal arteries. Full clinical descriptions of cohorts will be provided. Since abnormalities in renal vasculature can cause hypertension, this lack of renal artery description in imaging reports of patients with resistant hypertension may reveal missed opportunities in multidisciplinary communication and/or in the use of imaging to assess for causes of resistant hypertension. This missed opportunity for diagnosis of renovascular disease is similar to the low screening rates for primary aldosteronism as a cause of resistant hypertension, previously found at Stanford and across the US.
Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension
Authors: Li Guohua , Xu Ke , Xing Wenjuan , Yang Hongyan , Li Youyou , Wang Xinpei , Zhou Jiaheng , An Jiong , Dong Ling , Zhang Xing , Wang Li , Li Jia , Gao Feng
Published: September 2022

BACKGROUND:

Regular exercise has been recommended clinically for all individuals to protect against hypertension but the underlying mechanisms are not fully elucidated. We recently found a significant mitochondrial fragmentation in the vascular endothelium of hypertensive human subjects. In this study, we investigated whether exercise could restore endothelial mitochondrial dynamics and thus improve vascular function in hypertension.

METHODS:

Vascular endothelial mitochondrial morphological alterations were examined in patients with hypertension and hypertensive animal models. Furthermore, swimming exercise-induced endothelial mitochondrial dynamics and vascular function changes were investigated in spontaneously hypertensive rats (SHRs).

RESULTS:

Mitochondrial fragmentation with an elevated mitochondrial fission mediator Drp1 (dynamin-related protein-1) was observed in the mesenteric artery endothelium from hypertensive patients. A similar mitochondrial fragmentation with increased Drp1 expression were exhibited in the aortic endothelium of angiotensin II-induced hypertensive mice and SHRs. Interestingly, swimming exercise significantly reduced vascular Drp1 expression and alleviated endothelial mitochondrial fragmentation, thus improving blood pressure in SHRs. In cultured endothelial cells, angiotensin II exposure induced Drp1 upregulation, mitochondrial fragmentation and dysfunction, and reduced nitric oxide production, which was blunted by Drp1 genetic reduction or its inhibitor Mdivi-1. Mdivi-1 administration also ameliorated endothelial mitochondrial fragmentation, vascular dysfunction and blood pressure elevation in SHRs while swimming exercise plus Mdivi-1 treatment provided no additional benefits, suggesting that Drp1 inhibition may partially contribute to swimming exercise-conferred anti-hypertensive effects.

CONCLUSIONS:

These findings suggest that swimming exercise alleviates endothelial mitochondrial fragmentation via inhibiting Drp1, which may contribute to exercise-induced improvement of vascular function and blood pressure in hypertension.
Mineralocorticoid Receptor Antagonism by Finerenone Attenuates Established Pulmonary Hypertension in Rats
Authors: Tu Ly , Thuillet Raphaël , Perrot Julie , Ottaviani Mina , Ponsardin Emy , Kolkhof Peter , Humbert Marc , Viengchareun Say , Lombès Marc , Guignabert Christophe
Published: September 2022

Background:

We studied the ability of the nonsteroidal MR (mineralocorticoid receptor) antagonist finerenone to attenuate vascular remodeling and pulmonary hypertension using two complementary preclinical models (the monocrotaline and sugen/hypoxia rat models) of severe pulmonary hypertension.

Methods:

We first examined the distribution pattern of MR in the lungs of patients with pulmonary arterial hypertension (PAH) and in monocrotaline and sugen/hypoxia rat lungs. Subsequent studies were performed to explore the effect of MR inhibition on proliferation of pulmonary artery smooth muscle cells derived from patients with idiopathic PAH. To validate the functional importance of MR activation in the pulmonary vascular remodeling characteristic of pulmonary hypertension, mice overexpressing human MR (hMR+) were studied, and curative treatments with finerenone (1 mg/kg per day by gavage), started 2 weeks after monocrotaline injection or 5 weeks after Sugen injection were realized.

Results:

We demonstrated that MR is overexpressed in experimental and human PAH and that its inhibition following small interfering RNA-mediated MR silencing or finerenone treatment attenuates proliferation of pulmonary artery smooth muscle cells derived from patients with idiopathic PAH. In addition, we obtained evidence that hMR+ mice display increased right ventricular systolic pressure, right ventricular hypertrophy, and remodeling of pulmonary arterioles. Consistent with these observations, curative treatments with finerenone partially reversed established pulmonary hypertension, reducing total pulmonary vascular resistance and vascular remodeling. Finally, we found that continued finerenone treatment decreases inflammatory cell infiltration and vascular cell proliferation in monocrotaline and sugen/hypoxia rat lungs.

Conclusions:

Finerenone treatment appears to be a potential therapy for PAH worthy of investigation and evaluation for clinical use in conjunction with current PAH treatments.
Blood Pressure Fluctuation During Hospitalization and Clinical Outcomes Within 3 Months After Ischemic Stroke
Authors: Wang Ruirui , Liu Yang , Yang Pinni , Zhu Zhengbao , Shi Mengyao , Peng Yanbo , Zhong Chongke , Wang Aili , Xu Tan , Peng Hao , Xu Tian , Chen Jing , Zhang Yonghong , He Jiang
Published: September 2022

BACKGROUND:

Increased blood pressure (BP) variability is positively associated with the risks of cerebral small-vessel disease, cardiovascular events and death. However, no large clinical trials have been published to demonstrate the effect of BP fluctuations during hospitalization on clinical outcomes after ischemic stroke.

METHODS:

A total of 3972 patients with acute ischemic stroke from 26 participating hospitals were included in this study, and BP fluctuations were calculated using BP data collected during the hospitalization. The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months and secondary outcomes included death, vascular events, and composite outcomes (death or vascular events).

RESULTS:

Compared with the lowest quartile of systolic BP fluctuations, the adjusted odds ratio associated with the highest quartile was 1.33 ([95% CI, 1.05–1.68];
P
trend
=0.011) for primary outcome; the adjusted hazard ratios were 2.89 ([95% CI, 1.58–5.32];
P
trend
<0.001) for death, 1.48 ([95% CI, 0.83–2.65];
P
trend
=0.071) for vascular events, and 2.06 ([95% CI, 1.32–3.23];
P
trend
<0.001) for composite outcome. Similar results were found for diastolic BP. Multivariable adjusted restricted cubic spline analysis showed a linear relationship between systolic BP fluctuations and the primary outcome (
P
for linearity=0.0009).

CONCLUSIONS:

Larger BP fluctuations during hospitalization were associated with an increased risk of adverse outcomes at 3 months after ischemic stroke onset, independent of mean BP. These findings suggested that BP fluctuation should be a risk factor of adverse outcomes after ischemic stroke, which provided a new insight for BP management strategy.
Smartphone Application-Assisted Home Blood Pressure Monitoring Compared With Office and Ambulatory Blood Pressure Monitoring in Patients With Hypertension: the AMUSE-BP Study
Authors: Groenland Eline H. , Vendeville Jean-Paul A.C. , Bemelmans Remy H.H. , Monajemi Houshang , Bots Michiel L. , Visseren Frank L.J. , Spiering Wilko
Published: September 2022

Background:

The development of automated, smartphone application (app)-assisted home blood pressure monitoring (HBPM) allows for standardized measurement of blood pressure (BP) at home. The aim of this study was to evaluate the (diagnostic) agreement between app-assisted HBPM, automated office BP (OBP), and the reference standard 24-hour ambulatory BP monitoring (ABPM).

Methods:

In this open randomized 5-way cross-over study, patients diagnosed with hypertension were randomized to one of 10 clusters, each containing 5 BP measurement methods (ABPM, HBPM, attended OBP, unattended OBP, and unattended 30-minute BP) in different order.

Results:

In total, 113 patients were included. The average 24-hour ABPM was 126±11/73±8 mm Hg compared with 141±14/82±10 mm Hg with app-assisted HBPM, 134±13/80±9 mm Hg with unattended 30-minute BP, 137±16/81±11 mm Hg with attended OBP, and 135±15/81±10 mm Hg with unattended OBP monitoring. Diagnostic agreement between app-assisted HBPM and 24-hour ABPM for diagnosing sustained (OBP >140/90 mm Hg and ABPM ≥130/80 mm Hg or HBPM ≥135/85 mm Hg), white-coat (OBP ≥140/90 mm Hg and ABPM <130/80 mm Hg or HBPM <135/85 mm Hg), and masked hypertension (OBP <140/90 mm Hg and ABPM ≥130/80 mm Hg or HBPM ≥135/85 mm Hg) was fair-to-moderate (κ statistics ranging from 0.34 to 0.40). App-assisted HBPM had high sensitivities (78%–91%) and negative predictive values (90%–97%) for diagnosing sustained and masked hypertension.

Conclusions:

This study showed a considerable (diagnostic) disagreement between app-assisted HBPM and ABPM. App-assisted HBPM had high sensitivity in the diagnosis of sustained and masked hypertension and may therefore be used as complementary to, but not a replacement of, ABPM.
High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients
Authors: Trimarco Valentina , Izzo Raffaele , Morisco Carmine , Mone Pasquale , Virginia Manzi Maria , Falco Angela , Pacella Daniela , Gallo Paola , Lembo Maria , Santulli Gaetano , Trimarco Bruno
Published: September 2022

Background:

Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension.

Methods:

To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy.

Results:

We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients.

Conclusions:

Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.
Walk the Talk: Current Evidence for Walking Recovery After Stroke, Future Pathways and a Mission for Research and Clinical Practice
Authors: Moore Sarah A. , Boyne Pierce , Fulk George , Verheyden Geert , Fini Natalie A.
Published: September 2022

Achieving safe, independent, and efficient walking is a top priority for stroke survivors to enable quality of life and future health. This narrative review explores the state of the science in walking recovery after stroke and potential for development. The importance of targeting walking capacity and performance is explored in relation to individual stroke survivor gait recovery, applying a common language, measurement, classification, prediction, current and future intervention development, and health care delivery. Findings are summarized in a model of current and future stroke walking recovery research and a mission statement is set for researchers and clinicians to drive the field forward to improve the lives of stroke survivors and their carers.
Neural Basis of the Implicit Learning of Complex Artificial Grammar with Nonadjacent Dependencies
Authors: Ling Xiaoli , Sun Peng , Zhao Lu , Jiang Shan , Lu Yang , Cheng Xuemei , Guo Xiuyan , Zhu Xia , Zheng Li
Published: September 2022

The capacity for the implicit learning/processing of complex grammar with nonadjacent dependencies is an important feature of human language learning. In this fMRI study, using an implicit AGL paradigm, we explored the neural basis of the implicit learning of the nonadjacent dependency rule, disentangling from sequence-based chunk knowledge (i.e., local sequential regularities or substring) by focusing on the low chunk strength items (which were naturally less similar to training strings), based on tracking neural responses during training and test phases. After listening to and memorizing a series of strings of 10 syllables generated from nonadjacent artificial grammar in the training phase, participants implicitly acquired the knowledge of grammar and chunks. Regarding grammaticality, Broca's area was specifically related to low chunk strength grammatical strings relative to nongrammatical strings in the test phase. This region showed decreased activity with time in the training phase, and a lesser decrease in activity was associated with higher performance in grammar learning. Furthermore, Broca's area showed significantly higher strength of functional connectivity with the left superior temporal gyrus in the low chunk strength grammatical string compared with nongrammatical strings, and this functional connectivity increased with the training time. For the chunks, the performance of accurate discrimination of high chunk strength from low chunk strength nongrammatical strings was predicted by hippocampal activity in the training phase. Converging evidence from the training and test phases showed that Broca's area and its functional connectivity with the left superior temporal gyrus were engaged in the implicit learning/processing of the nonadjacent dependency rule, separating the effects of chunks.
Dissociation of Writing Processes: A Functional Magnetic Resonance Imaging Study on the Neural Substrates for the Handwritten Production of Chinese Characters
Authors: He Jieying , Brehm Laurel , Zhang Qingfang
Published: September 2022

Writing is an important way to communicate in everyday life because it can convey information over time and space, but its neural substrates remain poorly known. Although the neural basis of written language production has been investigated in alphabetic scripts, it has rarely been examined in nonalphabetic languages such as Chinese. The present functional magnetic resonance imaging study explored the neural substrates of handwritten word production in Chinese and identified the brain regions sensitive to the psycholinguistic factors of word frequency and syllable frequency. To capture this, we contrasted neural activation in “writing” with “speaking plus drawing” and “watching plus drawing.” Word frequency (high, low) and syllable frequency (high, low) of the picture names were manipulated. Contrasts between the tasks showed that writing Chinese characters was mainly associated with brain activation in the left frontal and parietal cortex, whereas orthographic processing and the motor procedures necessary for handwritten production were also related to activation in the right frontal and parietal cortex as well as right putamen/thalamus. These results demonstrate that writing Chinese characters requires activation in bilateral cortical regions and the right putamen/thalamus. Our results also revealed no brain activation associated with the main effects of word frequency and syllable frequency as well as their interaction, which implies that word frequency and syllable frequency may not affect the writing of Chinese characters on a neural level.
Assessing the importance of artificial canopy bridge design for Costa Rican monkeys in an experimental setting
Authors: Narváez-Rivera Giselle M. , Lindshield Stacy M.
Published: September 2022

Although artificial crossing structures are increasingly implemented by conservationists and wildlife managers to connect fragmented wildlife habitat, the study of artificial crossing structure design, particularly of canopy bridges, is an emerging field of study in primatology. We address this issue by evaluating five competing bridge models with varying width, material stiffness, and substrate spacing. We assessed bridge preference and performance by sampling the behavior of three species of Costa Rican monkeys (Alouatta palliata: n = 4, Ateles geoffroyi: n = 3, Cebus imitator: n = 3). In a semi-wild setting, we used focal individual sampling with instantaneous recording once every minute for ten-minute intervals and all occurrences sampling whenever study subjects used the bridge. We hypothesized that monkeys prefer bridges that are more stable, and that are made of materials that resemble tree branches. During nearly 37 sampling hours we observed 119 crossing events. We found that study subjects prefer bridge models that are built using more rigid materials, such as the bamboo pole bridge, or wider bridges that offer more stability than narrower bridges. The bridge type and the materials used to build the bridges are both significant predictors of bridge use. While preference for bridges and their performance varies by species, the bamboo pole bridge model and the horizontal mesh bridge were preferred and performed best in our study. The simple liana bridge model was the least preferred by all species and performed poorly in comparison to the other models. Our findings will help us better understand how design and materials impact the use of canopy bridges by monkeys, which can help improve biological corridors and offer new information for the management and conservation of primates living near infrastructure corridors and other kinds of dangerous matrix.
Aristotle’s Account of the Immobility of Place: A Cold Case
Authors: Quarantotto Diana
Published: September 2022

At least since the Neoplatonic commentators, Aristotle’s thesis that place is immobile has been considered a serious problem for his theory of place and locomotion. This diagnosis, however, is essentially based on a single passage (212a14–21)—the famous passage on the boat moving in a river—which interpreters find both central and obscure or imprecise, and which has so far resisted a literal reading. I tackle this issue by considering texts hitherto neglected by scholars and propose a new and charitable interpretation, showing the consistency of Aristotle’s thesis of the immobility of place with his general theory of change, as well as a fresh reading of ll. 212a14–21 that stays close to the text. Further, I argue that there are good reasons to believe that the interpretation I put forward is the most ancient one.
Ideological Uniformity and Political Integralism in Europe and Indonesia: A Kuyperian Critique
Authors: Un Antonius Steven
Published: September 2022

This article presents a Kuyperian critique of ideological uniformity and political integralism in Europe and Indonesia. The background of Kuyper’s articulation of the principle of sphere sovereignty was his struggle with the liberals, the French Revolution, and the German idea and application of state sovereignty. Kuyper struggled with the liberals because he rejected ideological uniformity. He struggled with the ideals of the French Revolution because he rejected popular sovereignty and, later on, political integralism. Kuyper’s rejection of ideological uniformity and political integralism resulted in the articulation of the principle of sphere sovereignty. Such uniformity and integralism also characterized Suharto’s leadership in twentieth-century Indonesia, especially his doctrine of Pancasila as the only basis for the state and civil society and his ideology of the integralist state of Indonesia. I criticize those doctrines from the perspective of Kuyper’s principle of sphere sovereignty.
Republican Universalism at the Test of French Multicultural Society
Authors: Cicchelli Vincenzo , Octobre Sylvie
Published: September 2022

While the trial of modernity and its legacies, the rise of anti-universalistic discourses, and the temptations of identitarian closures are common Western trends, this paper will specifically focus on the French case, as its republican assimilationist model has been very much infused with universalism and endures many tensions facing multicultural society. By focusing on the arguments mobilized by young French adults to solve the tensions between republican universalism and national particularism, as well as envisioning social cohesion, we analyze their narratives and shed light on four “spirits”: Homo Nationalis, embodying a nationalistic passion for the homeland; Homo Civicus, expressing deep commitment to the res publica and the common good; Homo Culturalis, demanding recognition of minority cultures; and Homo Pontifex (the “bridge builder”), encouraging cosmopolitanism and a love of humanity.
Psychological Experiences of Elderly Patients With Covid-19 Diagnosis in Intensive Care: A Qualitative Study
Authors: DEMIR Gökçe , SEKI ÖZ Hilal
Published: September 2022

In the study, it was aimed to determine the experiences of elderly COVID-19 patients hospitalized in intensive care units. The study was conducted based on the phenomenological design, one of the qualitative research methods. In-depth interviews were conducted using a semi-structured interview form with 15 participants, who were determined by the homogeneous and criterion sampling methods, two of the purposive sampling methods. Data were analyzed using Colaizzi’s seven-step method. After the interviews, four themes were determined: intensive care experiences, importance of nursing care, intensive care environment and coping mechanisms related to COVID-19 disease, and post-intensive care realizations. In addition, 13 sub-themes were determined. This study provided a better understanding of the psychological experiences of elderly individuals during the disease, who have been hospitalized in intensive care unit and survived COVID-19.
The Handmaid Still in the Classroom? Using The Handmaid’s Tale in Sociology of Gender
Authors: Prince Barbara F.
Published: September 2022

Sociologists are uniquely positioned to use science fiction literature in the classroom. Despite students reading less, the science fiction novel The Handmaid’s Tale is more popular than ever. I obtained the data for this study through content analysis of 108 student journal entries in a sociology of gender course at a small liberal arts college. Journal entries were analyzed for identification and application of class concepts in addition to an overall rating of The Handmaid’s Tale. Students successfully identified and connected 58 distinct class concepts to the novel. The most common concepts that students identified were gender stereotype, doing gender, and patriarchy. In addition, students enjoyed the novel and rated it highly. The average rating was 4.2 stars out of 5. Results from this study suggest that science fiction remains relevant and useful in the contemporary sociology classroom.
Outlier Detection Using t-test in Rasch IRT Equating under NEAT Design
Authors: Liu Chunyan , Jurich Daniel
Published: September 2022

In equating practice, the existence of outliers in the anchor items may deteriorate the equating accuracy and threaten the validity of test scores. Therefore, stability of the anchor item performance should be evaluated before conducting equating. This study used simulation to investigate the performance of the t-test method in detecting outliers and compared its performance with other outlier detection methods, including the logit difference method with 0.5 and 0.3 as the cutoff values and the robust z statistic with 2.7 as the cutoff value. The investigated factors included sample size, proportion of outliers, item difficulty drift direction, and group difference. Across all simulated conditions, the t-test method outperformed the other methods in terms of sensitivity of flagging true outliers, bias of the estimated translation constant, and the root mean square error of examinee ability estimates.
Tax-Related Restatements and Tax Avoidance Behavior
Authors: Adams Mollie T. , Inger Kerry K. , Meckfessel Michele D. , Maher John J.
Published: September 2022

Our research empirically examines the relationship between tax avoidance and the likelihood of incurring a tax-related restatement, as well as the effects tax restatements have on future tax avoidance behavior. We predict and find that the association between tax avoidance and the likelihood of a tax-related restatement is nonlinear. Specifically, both relatively high levels and relatively low levels of tax avoidance compared to peer firms increase the likelihood of incurring a tax-related restatement. We consider whether the increased likelihood for high avoiders is attributable to obfuscation necessary to escape detection of tax avoidance or weak corporate governance. For high avoiders, we find evidence that both obfuscation and weak corporate governance may contribute to the likelihood of a tax-related restatement. As low avoiders should not need to obfuscate, we focus on corporate governance and find an increased likelihood when governance is weak. In response to a tax-related restatement announcement, we document a decline in tax avoidance for firms that have relatively high tax avoidance prior to the restatement announcement. We attribute this to the increased level of Internal Revenue Service (IRS) monitoring and strengthening of corporate governance that we observe post-restatement announcement. In contrast, we do not find evidence that low avoidance firms alter their tax avoidance after a tax-related restatement announcement, consistent with our finding that corporate governance does not improve post-restatement for low avoiders.
Mitral valve repair and tricuspid annuloplasty for Coffin–Lowry syndrome
Authors: Wakami Tatsuto , Yoshizawa Kosuke , Maeda Toshi , Mori Otohime , Tamura Nobushige
Published: September 2022

Coffin–Lowry syndrome is a rare X-linked disorder that shows a varied clinical presentation. We report cardiac involvement, particularly abnormalities of mitral valve morphology, in a 14-year-old male adolescent with a known diagnosis of Coffin–Lowry syndrome, who presented with easy fatigability. Echocardiography revealed severe mitral and moderate tricuspid regurgitation, and the papillary muscles were attached to the base of the left ventricle. We performed tricuspid annuloplasty and mitral valve repair using two artificial chordae and a semi-rigid full ring. The patient's postoperative course was uneventful. Postoperative echocardiography revealed reduced mitral regurgitation, and his cardiac failure improved.
Cognition-enhancing effect of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in the 5 × FAD transgenic mouse model of Alzheimer’s pathology
Authors: Dai Wei , Yao Ru-Meng , Mi Tian-Yue , Zhang Li-Ming , Wu Hong-liang , Cheng Jin-Bo , Li Yun-Feng
Published: September 2022

Background:

Intracerebral translocator protein 18 kDa (TSPO) mediates the transport of cholesterol from cytoplasm to mitochondria and activation of microglia. The change of TSPO and the dysfunction of microglia are closely related to the pathogenesis of Alzheimer’s disease (AD).

Aims:

This study aimed to investigate the effects of microglial TSPO and its selective ligand YL-IPA08 on the cognitive function of transgenic mice in 5 × familial Alzheimer’s disease (FAD) mouse model of AD.

Methods:

The TSPO knockout 5 × FAD transgenic mice were bred, and tested by Morris water maze. The effects of YL-IPA08 on cognitive abilities and expression of Aβ in 5 × FAD mice were also explored into.

Results:

The latency of escape by TSPO knockout 5 × FAD mice was significantly prolonged compared with the 5 × FAD group, indicating that the cognitive impairment of mice aggravated. With the attenuated phagocytic ability of microglia, the deposition of Aβ in prefrontal cortex of TSPO knockout 5 × FAD mice increased, and the expression of proinflammatory factors (IL-1β, TNF-α, IL-6) were upregulated. In addition, YL-IPA08 significantly reduced the latency of escape by 5 × FAD mice, increased the number of times of crossing over the platform by mice, and inhibited the deposition of Aβ in the prefrontal cortex of 5 × FAD mice without affecting the cleavage of APP.

Conclusion:

Our findings suggested that TSPO knockout in 5 × FAD mice inhibited microglial phagocytosis, promoted Aβ deposition and neuroinflammation, and aggravated cognitive dysfunction in AD mice. YL-IPA08 had a significant cognition-enhancing effect in 5 × FAD transgenic mice, which might provide a new basis for potential drug candidates in AD treatment.
Longitudinal Associations Between Depressive Symptoms and Preference for Solitude Among Chinese Early Adolescents: Separating Between-Person from Within-Person Effects
Authors: Zheng Kejun , Coplan Robert J. , Chen Xinyin , Bian Yufang
Published: September 2022

The goal of this study was to explore longitudinal associations between preference for solitude (PFS) and depressive symptoms among early adolescents in mainland China, with a focus on separating between-person and within-person effects using a random intercept cross-lagged panel model (RI-CLPM). Participants were N = 1039 Chinese early adolescents ( Mage= 12.37, 46.1% girls, at Time 1), who completed annual self-reports of depressive symptoms and peer-nominations of PFS over a 3-years period. Results revealed that fluctuations in depressive symptoms consistently predicted fluctuations in PFS 1 year later, but not vice versa, supporting a symptoms-driven model. Findings are discussed in terms of the role of depressive symptoms in promoting subsequent PFS among early adolescents.
Going Vertical with Love Thy Neighbor: Exegetical Use of Scripture in Leviticus 19.18b
Authors: Schnittjer Gary Edward
Published: September 2022

When focusing on the scriptures themselves, the horizontal context of a given text refers to the surrounding verses, paragraphs, chapters, and book. Vertical context refers to an exegetical allusion to an earlier scriptural tradition within the text itself. In spite of intense, ongoing study of Lev. 19.18b within its horizontal contexts, the vertical context within this verse has been ignored. The present study defines vertical context and how it functions as a basis to interpret Lev. 19.18b. After investigating how vertical context bears on Lev. 19.18b, the passage is explained in relation to the intersection of its vertical and horizontal contexts.
Weapon Confusion: TASER CEWs, Firearms, and Human Error Theories
Authors: Williams Howard E.
Published: September 2022

Norman's human action theory and Reason's human error theory provide frameworks to analyze and to understand weapon confusion wherein a police officer mistakenly draws and discharges a firearm rather than a stated intent of deploying a TASER CEW. Review of publicly available information culminated in qualitative analysis of 20 TASER CEW/firearm confusion shootings that revealed evidence of capture error and action execution slips. Although changes in policy and training have not eliminated such errors, there is evidence they might have had some success in reducing the frequency. Systematic and simultaneous changes in weapon design, policies, training, and procedures might be necessary to reduce or eliminate weapon confusion but must be carefully assessed to avoid negative unintended consequences.