bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P192: Is Auscultation Adequate To Estimate Blood Pressure Responses Related To Body Position Changes?
Authors: Alpert Bruce , Vybornova Anna , Wurzner-Ghajar Arlene , Polychronopoulou Erietta , Fallet Sibylle , Sola Josep , Wuerzner Grégoire
Published: September 2020

Double-blinded auscultation is the current reference to validate new devices in the sitting position. There are few data to tell whether it should be used for device validation in other body positions, as the Korotkoff sounds can be affected by changes in vascular tone. In this study, we recorded the BP response to orthostatic posture change (standing to supine) in 75 subjects, aged between 21 and 65 years old. Systolic (SBP) and diastolic (DBP) were measured on the left upper arm by auscultation by two independent blinded observers before and 150s after posture change. In case the observers did not agree, i.e. readings differed more than 4 mmHg, the measurement was repeated. Beat-to-beat BP values were measured on the ipsilateral middle finger with Nexfin (BMEYE, The Netherlands). Because Nexfin measurements were not available during upper-arm cuff inflation, the mean of the values in a 30s window prior to auscultation onset was used for the analysis. The distribution of the BP responses to posture change was characterized in terms of median, 10
th
and 90
th
percentiles (see Table). The response was considered consistent if these percentiles were on the same side of zero. Neither auscultation nor Nexfin detected any consistent posture-related changes in SBP when going from standing to supine. Nexfin detected a consistent decrease in DBP. Auscultation detected no consistent posture-related change. Compared to volume-clamp, auscultation was not able to detect any consistent changes in DBP during orthostatic challenge. Our study suggests that the use of Korotkoff sounds to estimate BP in body positions other than sitting may not be appropriate.
Abstract P198: Vitamin D Supplementation Improves Autonomic Response To Head Up Tilt In Adolescents Suffering From Orthostatic Intolerance
Authors: Shaltout Hossam A
Published: September 2020

Background:
We have previously shown in a group of adolescents who are suffering from orthostatic intolerance (OI) and syncope that they exhibited impairment in autonomic function in supine position and greater loss of baroreflex sensitivity (BRS) and heart rate variability (HRV) measures upon head up tilt (HUT). They also had low vitamin D level that correlated with the severity of symptoms on tilt. In this pilot study we hypothesized that vitamin D supplementation to normal levels will improve the autonomic response to change in position.

Methods:
In a pilot group of eight female adolescents (mean age= 16.0 years) who are vitamin D deficient, head up tilt was done at baseline and after two months of vitamin D supplementation (2000-5000 IU daily based on baseline level). Heart rate, blood pressure, BRS measured as Sequence Up (parasympathetic) and Sequence down (sympathetic), HRV measured as SDNN and rMSSD, and sympathovagal balance (LF/HF ratio) were assessed both in supine and HUT positions.

Results:
As shown in the table, compared to baseline, vitamin D supplementation improved vitamin D level, minutes standing on tilt, BRS, HRV and sympathovagal balance measures at baseline and reduced the loss in BRS and HRV measures upon standing. There were no changes in blood pressure measures between pre and post treatment.

Conclusions:
Vitamin D supplementation for two months restored vitamin D to normal levels and was associated with improvement in the hemodynamic response to standing. These data provide evidence of potential therapeutic benefit of vitamin D supplementation for patients suffering from orthostatic intolerance who are vitamin D deficient,
Abstract P199: Effectiveness Of Intensive Lipid-lowering Therapy With Statins In Type 2 Diabetes Mellitus Patients With Poorly Controlled Blood Pressure
Authors: Ikeda Shota , Shinohara Keisuke , Enzan Nobuyuki , Matsushima Shouji , Tohyama Takeshi , Funakoshi Kouta , Kishimoto Junji , Itoh Hiroshi , Komuro Issei , Tsutsui Hiroyuki
Published: September 2020

Introduction:
Control of blood pressure (BP) is associated with decreased risk of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Lowering the level of low-density lipoprotein cholesterol (LDL-C) by statins is also effective to reduce CV events in T2DM patients with hyperlipidemia. In this study, we examined whether the effectiveness of statin lipid-lowering therapy was affected by baseline BP level in T2DM patients in a primary prevention setting.

Methods:
The EMPATHY study was a randomized controlled trial investigating the effects of statin intensive therapy targeting LDL-C <70 mg/dL compared to standard therapy targeting LDL-C ≥100 to <120 mg/dL in T2DM patients with diabetic retinopathy and hyperlipidemia without known CV diseases. In this post-hoc subgroup analysis, a total of 4980 patients were divided into two groups based on baseline BP: high BP (systolic BP ≥130 mmHg and/or diastolic BP ≥80 mmHg) and non-high BP (systolic BP <130 mmHg and diastolic BP <80 mmHg) groups. CV events were defined as composite of cardiac, cerebral, renal, and vascular events.

Results:
At baseline, mean systolic and diastolic BP values were 141.7 and 78.3 mmHg in high BP group (n=3335) and 120.2 and 67.9 mmHg in non-high BP group (n=1645). Compared to non-high BP group, the proportion of patients with diabetic nephropathy (55.5 % vs 46.6 %), body mass index (26.1 kg/m
2
vs 24.8 kg/m
2
), HbA1c (7.82 % vs 7.67 %), and LDL-C (131.3 mg/dL vs 129.6 mg/dL) were significantly higher in high BP group. During a median follow-up of 36.8 months, 281 CV events were observed. In high BP group, statin intensive therapy was associated with low risk of CV events (HR 0.70, 95% CI 0.54-0.92, p=0.011) compared to standard therapy after adjustment. In non-high BP group, no such association was observed. Interaction between BP group and statin therapy was significant in CV events (p=0.036).

Conclusion:
Compared to statin standard therapy, statin intensive therapy targeting LDL-C <70 mg/dL significantly reduced CV events in the primary prevention setting among T2DM patients with BP ≥130/80 mmHg, but not among those with BP <130/80 mmHg.
Abstract P202: Providers' Perspectives On Adherence To Antihypertensive Treatment In Vietnamese Patients
Authors: Vo David , Do Mai
Published: September 2020

Background:
Medical adherence is one of the most effective ways of controlling hypertension among those under treatment. Vietnamese Americans have a high prevalence of hypertension and low rates of adherence to treatment. Yet there is a minimal body of literature that addresses this condition among Vietnamese Americans.

Objectives:
Our principle objectives are: 1) identify the level of adherence and 2) identify the attitudes, beliefs, and behaviors that influence adherence to antihypertensive treatment among Vietnamese in New Orleans.

Methods:
The first phase of the study examined 250 randomly selected medical records of Vietnamese hypertensive patients from a local community clinic to determine the adherence rate. Semi-structured interviews were conducted with four providers that work at the same clinic who treat these patients. Providers were asked about their perceptions of factors that influence antihypertensive treatment adherence in Vietnamese patients, and potential points of interventions. A thematic analysis of the semi-structured interviews was conducted.

Results:
The medical record review identified 20.4% (51 out of 250) of patients were non-adherent to antihypertensive treatment. The common theme that emerged from the interviews was health illiteracy, particularly limited access to knowledge in the native language was a major factor to non-adherence. Patients preferred to seek information from loved ones and to utilize therapies outside of Western medicine. Factors that increased adherence included having patients track blood pressure measurements and establishing trusting provider-patient relationships.

Discussion/Conclusions:
Patient education is a critical component to adherence to antihypertensive treatment in Vietnamese patients. Language barriers and limited knowledge about the disease are significant problems that need to be addressed to improve the rate of adherence. The interview data will guide the remainder of the study where we will interview patients to better understand what influences adherence, and what approaches to improving adherence might be appropriate for Vietnamese patients.
Abstract P203: Insights To Lesion Formation For Percutaneous Renal Denervation: Human And Porcine Histological Analyses
Authors: Kandzari David , Tunev Stefan , Schlaich Markus P , LEE David P , Finn Aloke , Mahfoud Felix , Melder Robert , TRUDEL Julie , Coates Paul , Sharp Andrew S
Published: September 2020

Background:
The safety and efficacy of radiofrequency (RF) renal denervation (RDN) have been demonstrated in multiple randomized trials. We performed histological analyses in a swine model and human cadavers to investigate RF lesion geometry, morphology and location in the context of local anatomic structures and describe their impact on procedural outcomes.

Methods:
The Symplicity Spyral catheter was used to perform RDN in 164 renal arteries from healthy swine terminated at 7 days post-treatment. Lesion characteristics were determined by semi-quantitative histology. Renal nerve functionality was measured by quantitative immunohistochemistry and correlated to renal norepinephrine. In addition, we investigated the retroperitoneal space in 10 human cadavers to determine the relative location of extravascular tissues.

Results:
In the swine model, RF lesions developed exclusively in the perivascular adipose tissue which contains the renal nerves. Lesions were irregularly shaped due to inherent sparing of surrounding perfused structures, such as veins and lymph nodes. Maximum depth of the irregularly shaped RF lesions was 6.8±2.5 mm, and mean depth was 3.9±2.4 mm. Renal norepinephrine levels were lowest when >80% of renal nerves were ablated (
Figure
). Reendothelialization of the lesion area was >99% within 7 days. In humans, only 0.3% of renal nerves were localized on the opposite side of the renal veins.

Conclusion:
Patterns of RF RDN are uniquely influenced by electrical and thermal conduction properties of tissues surrounding the renal arteries. Maximal reduction of renal norepinephrine content requires ablation of at least 80% of the renal nerves.
Abstract P210: Progesterone Induced Blocking Factor Blockade Increases Inflammation And Markers Of Endothelial Dysfunction In Pregnant Rats
Authors: Amaral Lorena M , Witcher Alexis , Comley Kyleigh , Ibrahim Tarek , Lamarca Babbette B
Published: September 2020

Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity in the U.S. While the pathogenesis remains unclear, PE is characterized by new onset hypertension associated with progesterone deficiency, elevated cytolytic natural killer cells (cNK), inflammation, and endothelial dysfunction. Progesterone is essential in the initiation and maintenance of pregnancy. We have shown that progesterone supplementation regulates endothelial function and suppresses endothelin-1 (ET-1) and stimulates nitric oxide (NO) in response to placental ischemia during pregnancy. In addition, progesterone signals the synthesis and release of progesterone induced blocking factor (PIBF) from lymphocytes in order to regulate the proinflammatory balance of early pregnancy. However the role of PIBF in PE pathology is not well examined. This study was designed to test the hypothesis that inhibition of PIBF causes inflammation and increases markers of endothelial dysfunction and hypertension during pregnancy. Rabbit anti-PIBF IgG (0.25, low dose-LD or 0.50 mg/mL, high dose-HD) was administered intraperitoneal on gestation day (GD) 15 to normal pregnant Sprague Dawley (NP) rats, on GD 18 carotid catheters were inserted and on GD 19 blood pressure (MAP) and samples were collected. MAP in NP rats (n=7) was 99
+
3 mmHg, which increased to 116
+
2 in NP+ anti-PIBF LD (n =10) and 113
+
4 mmHg in NP+ anti-PIBF HD (n=6), p<0.05. Plasma TNF-alpha levels were 35
+
8 pg/mL in NP rats and increased to 84
+
21 pg/mL in NP+ Anti-PIBF HD (n=4), p<0.05. Circulating total NK cells were 67
+
11 in NP rats (n=4), which decreased to 36
+
4 in NP+ Anti-PIBF HD however, cytolytic NK cells were 0.6
+
0.2 in NP which were increased to 3.0
+
1 in NP+ Anti-PIBF HD, p<0.05. Importantly, circulating NO levels were 44
+
11 μM in NP rats (n=5), which significantly decreased to 21
+
1 μM in NP+ Anti-PIBF (n=6) HD, p<0.05. Moreover, renal cortex PPET-1 levels increased 15 fold in NP+ Anti-PIBF (n=6) HD compared to NP rats (n=5). Our study demonstrates that PIBF blockade causes hypertension and inflammation and signs of endothelial dysfunction, all of which are associated with PE, thus indicating the importance of progesterone signaling pathways during healthy pregnancy.
Abstract P213: Placental Ischemia-Stimulated Natural Killer Cells Contribute To Hypertension, Vascular Dysfunction, And Intrauterine Growth Restriction In Pregnant Rats
Authors: Travis Olivia K , Baik Cedar , Tardo Geilda A , Amaral Lorena M , Jackson Carmilya , Greer Mallory , Giachelli Chelsea , Williams Jan M , Cornelius Denise C
Published: September 2020

The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia mimics many characteristics of preeclampsia (PE) such as hypertension (HTN), intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). We have previously shown that natural killer (NK) cell depletion in RUPP rats improves PE pathophysiology and that RUPP NKs have a 5-fold increase in cytotoxicity vs normal pregnant NKs. In this study, we tested the hypotheses that (1) RUPP stimulated NKs play a direct role in causing HTN and IUGR in pregnant rats and (2) normal pregnant control (Sham) NKs attenuate HTN and IUGR in RUPP rats. NKs were isolated from the placentas of Sham and RUPP rats on gestation day (GD) 19. On GD14, vehicle or 5x10
6
RUPP NKs were infused i.v. into a subset of Sham rats, and vehicle or 5x10
6
Sham NKs were infused i.v. into a subset of RUPP rats. On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler Ultrasound; GD19, cNKs were quantified via flow cytometry and MAP, fetal weight, and blood were acquired. Plasma VEGF and sFlt-1 were measured via ELISA. Placental cNKs (% gated) increased from 3±1% in Sham to 19±5% in RUPP and 21±4% in Sham+RUPP NK (p<0.05 vs Sham), and decreased to 3±1% in RUPP+Sham NK (p<0.05 vs RUPP). Circulating cNKs also followed this trend. MAP increased from 102±1 mmHg in Sham to 130±2 mmHg in RUPP and 121±2 mmHg in Sham+RUPP NK (p<0.05 vs Sham), and was blunted to 113±1 mmHg in RUPP+Sham NK (p<0.05 vs RUPP). Fetal weight decreased from 2.4±0.04 g in Sham to 2.1±0.07 g in RUPP and 2.1±0.03 g in Sham+RUPP NK (p<0.05 vs Sham), and this was normalized to 2.3±0.03 g in RUPP+Sham NK (p<0.05 vs RUPP). UARI increased from 0.56±0.05 in Sham to 0.75±0.06 in RUPP and 0.76±0.05 in Sham+RUPP NK (p<0.05 vs Sham), and decreased to 0.64±0.05 in RUPP+Sham NK (p<0.05 vs RUPP). Circulating sFlt-1 increased from 76±15 pg/mL in Sham to 1391±424 pg/mL in RUPP (p<0.05 vs Sham), 780±256 pg/mL in Sham+RUPP NK, and decreased to 67±8 pg/mL in RUPP+Sham NK (p<0.05 vs RUPP). Furthermore, circulating VEGF decreased in RUPP and Sham+RUPP NK compared to Sham (p<0.05), and increased in RUPP+Sham NK (p<0.05 vs RUPP). These data demonstrate a direct role for cNKs to mediate vascular dysfunction in PE and for normal NKs to promote positive maternal and fetal outcomes.
Abstract P225: Rupp Rat Model Cd4+ T Cells Activate Nk Cells And Cause Mitochondrial Oxidative Stress And Hypertension In Normal Pregnant Rats
Authors: Deer Evangeline M , Reeve Kristin , Amaral Lorena M , Vaka Venkata Ramana , Franks Michael , Fitzgerald Sarah , Herrock Owen , Ibrahim Tarek , Lamarca Babbette B
Published: September 2020

Preeclampsia (PE) is new onset hypertension during pregnancy and is associated with elevated inflammatory response such as CD4+ T cells, NK cells, and cytokines. We have previously shown women with PE exhibit increases in circulating and placental CD4+T cells and placental mitochondrial (mt) dysfunction/ROS compared to normal pregnant (NP) women. The Reduced Uterine Perfusion Pressure (RUPP) rat model produces many characteristics of PE such as hypertension, increases in CD4+ cells, increases in renal and placental NK cells, and mt dysfunction/ROS. We have previously demonstrated that RUPP CD4+T cells cause hypertension in NP rats, however the role of RUPP CD4+ T cells in stimulating NK cells to cause mt dysfunction/ROS are not elucidated. Therefore, we examined the effect of adoptive transfer of RUPP CD4+ T cells to activate NK cells in NP rats. Splenic CD4+ T cells were isolated from RUPP rats, cultured, and injected into NP rats on GD 13. On GD19, MAP values and blood/tissue samples were collected from both RUPP CD4+ T cell recipients and NP controls. Mitochondrial respiration and mtROS were measured in isolated mitochondria using the Oxygraph 2K and fluorescent microplate reader, respectively. A student’s t-test was used for statistical analysis. On GD19, MAP increased to 110±2 mmHg (n=13) in RUPP CD4+ T cell recipients compared to control NP rats 102±2 mmHg (n=7, p<0.05). Circulating cytolytic NK cells increased to 3±0.6% in RUPP CD4+ T cell recipients (n=8) compared to NP controls 0.3±0.2% (n=7, p<0.05). Placental state 3 (209.3±31.3 vs 422.7 ±83.3 pmol/sec/mg, p<0.05) and maximal (152.1±46.2 vs 229.7±58.9 pmol/sec/mg) and renal state 3 (133.4 ±21.4 vs 289.8±43.4 pmol/sec/mg, p<0.05) and maximal (61.8±18 vs 242.4±27.7 pmol/sec/mg, p<0.05) respiration rates, indicative of ATP production and electron transport chain efficacy respectively, were reduced with RUPP CD4+ T cells (n=6; n=9) compared to NP (n=5; n=5). Collectively, the data indicate that the adoptive transfer of RUPP CD4+ T cells stimulates cytolytic NK cells and placental and renal mitochondrial dysfunction/ROS during pregnancy as important mechanisms of hypertension in the pathophysiology of preeclampsia.

Keywords:
Preeclamspia, Hypertension, Oxidative stress
Abstract P226: The Analysis Of Regional Placental Hemodynamics Using Combined Photoacoustic Imaging And Contrast-enhanced Ultrasound
Authors: Elsangeedy Ebrahim , Rideout Danner Stephanie , Yamaleyeva Liliya M
Published: September 2020

Placental insufficiency is often associated with pregnancies at risk for fetal growth restriction or preeclampsia. We have previously demonstrated that three-dimensional ultrasound-guided photoacoustic imaging (PAI) is a sensitive tool for assessing regional variations in placental oxygenation in mice. However, whether changes in placental oxygenation determined by the PAI correlate with changes in placental perfusion is unknown and was tested in this study. PAI combines optical contrast of photoacoustic laser technology with a high spatial resolution of ultrasound. Placental vascular oxygen saturation (sO2) was quantified in C57Bl/6 mice by the PAI using Vevo 2100 LAZR instrument (Fujifilm, VisualSonics). 50 microliters of Vevo MicroMarker contrast agent was delivered via a bolus tail-vein injection. Placental perfusion parameters were determined at day 15 of gestation in C57Bl/6 mice. Our data demonstrated significantly greater oxygenation in the placental labyrinth versus maternal triangle area (53.01±1.7 vs. 42.7±4.2 % sO2; n=6, p<0.05). No regional differences were detected in relative blood flow in these mice (dB or a.u.). However “time-to-peak” (perfusion kinetics parameter) was greater in the labyrinth compared with maternal triangle area (2.3 times, p<0.05, n=5). Our data show that the overall blood flow is similar throughout the placenta at mid-late gestation, while the perfusion is greater in the labyrinth (fetal) side of the placenta consistent with greater vascularization of this area. Our data suggest that placental sO2 measured by the PAI is associated with coordinated changes in placental perfusion during late stages of mouse pregnancy. This approach provides a novel tool for non-invasively investigating placental environment and pregnancy outcomes particularly in pregnancies complicated by IUGR or preeclampsia.
Abstract P228: Mineralocorticoid Receptor Antagonist And Lipophilic Statin Reduce Urinary Kidney Injury Marker 1 (Kim-1) In Female Rats Receiving L-NAME And Angiotensin II
Authors: Caliskan Guzelce Ezgi , Huang Jiayan , Gholami Shadi K , Gawelek Kara Lynn , Mitchell Richard Neal , Pojoga Luminita , Romero Jose R. , Williams Gordon H. , K. Adler Gail
Published: September 2020

Statins have beneficial cardiovascular effects some of which appear to be cholesterol-independent and the mechanisms for these latter effects are still unclear. Urinary kidney injury molecule-1 (Kim-1) is a sensitive biomarker of acute renal injury and in clinical studies predicts cardiovascular disease. Aldosterone causes both cardiac and renal injury and a few studies suggest that aldosterone is associated with increased Kim-1. Therefore, in this study we used the N omega-nitro-L-arginine methyl ester (L-NAME)/Angiotensin II (AngII) model of cardiorenal injury to determine whether urinary Kim-1 correlates with the degree of cardiac injury/stroke and whether blockade of the mineralocorticoid receptor prevents increases in urinary Kim-1. Further, since our group reported previously that lipophilic statins, but not hydrophilic statins reduce aldosterone levels, we also asked whether administration of either a lipophilic or a hydrophilic statin affects Kim-1 levels.

To test the hypothesis, 8-10 week-old, female Wistar rats consuming liberal salt diet (1.6% Na
+
) were randomized to the following conditions for 14 days: control; L-NAME (0.2 mg/ml in drinking water)/AngII (225ug/kg/day for days 12-14 only); L-NAME/AngII + eplerenone (100 mg/kg/day p.o.); L-NAME/Ang II + pravastatin (hydrophilic statin-20 mg/kg/day p.o.); L-NAME/Ang II + simvastatin (lipophilic statin-20 mg/kg/day p.o.) groups.

Groups treated with L-NAME/AngII had significantly higher blood pressure, urine aldosterone and plasma aldosterone levels compared to control. L-NAME/AngII treatment increased cardiac injury/stroke composite score, including cardiac histopathology evaluation and stroke status, and

24 hour-urinary Kim-1 compared to control. Eplerenone reduced cardiac injury/stroke composite score (p=0.04) and both eplerenone and simvastatin reduced urinary Kim-1 (p=0.0046, p=0.031, respectively). Pravastatin had no effect on these damage markers. Urinary Kim-1 correlated with cardiac injury/stroke composite score (p<0.0001, spearman ranked correlation=0.67).

In conclusion, in a rat model of L-NAME/AngII induced cardiovascular injury, urinary Kim-1 predicts cardiac/stroke injury; eplerenone and simvastatin reduced urinary Kim-1.
Abstract P231: Macrophage Neutrophil Gelatinase-associated Lipocalin Has A Critical Role In Aldosterone-induced Renal Fibrosis Via The Ccl5-il4 Pathway.
Authors: Bonnard Benjamin , Genty Marie , Ibarrola Jaime F , Fernandez de Celis Amaya , Lopez-Andres Natalia , Jaisser Frederic
Published: September 2020

Introduction:
Neutrophil Gelatinase-Associated Lipocalin (NGAL) (or lipocalin 2) is a novel mineralocorticoid biotarget in the cardiovascular system. NGAL is also described as an acute renal lesion biomarker and NGAL serum concentration is associated with the severity of renal damages patients with a chronic kidney disease (CKD). Lipocalin2 (Lcn2) gene invalidation in a CKD mouse model protects from proteinuria and renal lesions.

Objective:
We hypothesized that the NGAL from macrophages promotes expression of chemoattractant molecules involved in renal lesions induced by mineralocorticoid excess.

Methods:
The role of Lcn2 was analyzed using full Lcn2 knock out mice (NGAL KO) challenged with uni-Nephrectomy, Aldosterone 200μg/kg/day, Salt 1% (NAS model) during 6 weeks. Assessment of CCL5/IL4 in kidney fibrosis were studied using maraviroc administration (50mg/kg/d in chow diet) or by injections of anti-IL4 antibody (600μg/week).

Results:
NAS induced a significant increase in the expression (relative values, mean±SEM, compared to 1 in the control samples, p<0.05) of extracellular matrix proteins such as collagen I (2.35±0.33), α-SMA (2.04±0.44) and fibronectin (3.38±0.42) in the kidney of WT mice associated with interstitial kidney fibrosis (6.49±0.70). These modifications were fully prevented by NGAL deletion. Expression of macrophages markers
F4/80
,
CD80
and
CD86
was increased (5.11±0.46, 4.84±0.19 and 5.22±0.45 respectively) in WT NAS mice and partly prevented in NGAL KO mice. Macrophages isolated from NGAL KO or WT mice were co-treated with aldosterone (10
-8
M) and NaCl (40mM). In WT macrophages, expression of
Lcn2
(2.81±0.30) and the
CCL5
chemokine (2.48±0.32) was increased. The increase of
CCL5
was prevented in NGAL KO macrophages. Such as total deletion of NGAL, CCL5 receptor blockade improved renal fibrosis and high level of Th2 CD4
+
cell markers induced by NAS. Neutralization of IL4 Th2 cytokine in NAS mice injected with anti-IL4 antibody blunted kidney fibrosis and overexpression of profibrotic proteins such as collagen I, α-SMA and fibronectin.

Conclusion:
NGAL produced by macrophages plays a critical role in renal interstitial fibrosis through CCL5/IL4 pathways in mice exposed to mineralocorticoid excess.
Abstract P245: Therapeutic Effects Of Mir-29b-Chitosan On Hypertension And Diabetic Complications
Authors: Jensen David M , Mangala Selanere , Sood Anil , Liu Jing , Kriegel Alison J , Usa Kristie , Widlansky Michael E , Liang Mingyu
Published: September 2020

MicroRNA miR-29 promotes endothelial function in human arterioles in part by targeting LYPLA1 and increasing nitric oxide production. Endothelial dysfunction is common in cardiovascular diseases such as hypertension and diabetic microvascular complications. In addition, miR-29 is a master inhibitor of extracellular matrix gene expression, which may attenuate fibrosis but could also weaken tissue structure. The goal of this study was to develop an effective miR-29 therapeutic for multiple cardiovascular diseases using mouse models. Substantial accumulation of miR-29b and effective knockdown of
Lypla1
in mouse tissues were achieved using a chitosan-packaged, chemically modified miR-29b mimic (miR-29b-CH) injected systemically at 200 μg/kg body weight. miR-29b-CH, injected once every three days, significantly attenuated angiotensin II-induced hypertension over two weeks (mean arterial pressure of 128 ± 5 vs 149 ± 5 mmHg, N = 7 Scr-CH, 8 miR-29b-CH p<0.05). In db/db mice, miR-29b-CH treatment for 12 weeks decreased cardiac (0.98 ± 0.13 vs 1.55 ± 0.17 % fibrosis) and renal (2.85 ± 0.28 vs 4.85 ± 0.47 % fibrosis) fibrosis and urinary albuminuria 0.0051 ± 0.0004 vs 0.0069 ± 0.0005 albumin/creatinine, N = 12 Scr-CH, 9 miR-29b-CH, p<0.05). In uninephrectomized db/db mice, the miR-29b-CH treatment for 20 weeks significantly improved myocardial performance index (0.36 ± 0.02 vs 0.57 ± 0.05) in addition to attenuating proteinuria (0.015 ± 0.004 vs 0.033 ± 0.005 protein/creatinine) (N = 8 Scr-CH, 8 miR-29b-CH, p<0.05). miR-29b-CH did not worsen abdominal aortic aneurysm in ApoE knockout mice treated with angiotensin II (33.7 ± 8.2 vs 29.8 ± 6.7% increase in suprarenal abdominal aorta diameter from baseline, N = 8 Scr-CH and 7 miR-29b-CH). miR-29b-CH caused aortic root fibrotic cap thinning (13.8 ± 2.5 vs 20.8 ± 1.8 % of total plaque area) in ApoE knockout mice fed a high cholesterol and high fat diet but did not worsen the necrotic zone (15.2 ± 1.4 vs 12.5 ± 1.0 % of total plaque area) or the mortality (11/12 control mice survived until end of study vs 10/12 miR-29b-CH treated, N = 8 Scr-CH, 7 miR-29b-CH). In conclusion, systemic delivery of low dose miR-29b-CH is an effective therapeutic for several forms of hypertension and diabetic complications in mice.
Abstract P246: Sex Differences In The Association Between Soluble Prorenin Receptor And Physiological And Cardiometabolic Risk Factors In Healthy Humans Varying In Age And Obesity
Authors: Arthur Gertrude , Pierce Gary L , DuBose Lyndsey E , Lane-cordova Abbi D , Jensen Nick , Wehrle Andrea , Stroud Amy , Yiannikouris Frederique B
Published: September 2020

The prorenin receptor (PRR), which regulates renin-angiotensin system in multiple tissues, can be cleaved to generate soluble PRR (sPRR) in plasma. sPRR concentrations vary with clinical conditions such as metabolic syndrome, pregnancy, chronic kidney disease and heart failure in humans. However, whether sPRR is associated with aging and healthy obesity in men and women is unknown. We aimed to evaluate if there are sex-specific associations of sPRR with cardiometabolic risk factors among healthy women and men varying in age and obesity. Circulating cardiometabolic, vascular and inflammatory risk factors and sPRR (via ELISA) were measured in unmedicated healthy men (n=55; age 39 ± 16 yrs; BMI 29 ± 4 kg/m2) and women (n=34; age 44 ± 16 yrs; BMI 30 ± 7 kg/m2) at the University of Iowa. Women were classified by menopausal status [pre-menopausal, pre-M (n=18) and post-menopausal, post-M (n=16)]. Independent
t
-test was used to compare means and pearson correlation was examined. In men, sPRR was not related to age, systolic blood pressure (SBP), BMI, cholesterol or endothelial function (brachial artery flow mediated dilation, FMD), but was correlated with plasma TNFα (r=0.50, P<0.05). sPRR was higher in overweight/obese (BMI ≥ 25 kg/m2) compared with non-obese men (n=48; 10.8 ± 0.4 vs. n=7; 8.3 ± 0.4 ng/ml, P<0.05). In women, sPRR did not correlate with BMI or SBP, but correlated with total cholesterol (r=0.49, P<0.05) and TNFα (r=0.49, P<0.05). sPRR correlated with age in women with a BMI<30 (r=0.54, P<0.05) but not a BMI ≥30 kg/m2. sPRR was significantly higher in post-M compared with Pre-M women independent of obesity or hypertension status (12.1 ± 0.5 vs. 10.1 ± 0.4 ng/ml, P<0.05). sPRR correlated with FMD only in obese women (%FMD: r=-0.50, P<0.05), indicating a relation of sPRR with endothelial dysfunction in obese women. Interestingly, sPRR was significantly higher in Pre-M compared with non-obese men and menopause further exacerbated the difference. In conclusion, sPRR is associated with TNFα in both men and women, but there are sex differences in the relation with BMI, age, cholesterol and endothelial function in humans. sPRR concentrations were higher in post-M compared with pre-M women, suggesting that PRR could contribute to cardiovascular risk in post-M women.
Abstract P250: Sphingosine-1-phosphate Receptor Agonist And Very Low-density Lipoprotein Regulate Aldosterone Production Via Lipin-1 In Human Adrenocortical Cells
Authors: Chowdhury Shinjini , Choudhary Vivek , Choudhary Mrunal , Chen Xunsheng , Bollag Wendy B
Published: September 2020

Aldosterone is considered to be a link between hypertension and obesity; obese individuals have high serum levels of both sphingosine-1-phosphate (S1P) and very low-density lipoprotein (VLDL). S1P has been reported to be a novel stimulator of aldosterone secretion and phospholipase D (PLD) activity. VLDL has also been shown to stimulate aldosterone production in multiple zona glomerulosa cell models via PLD. PLD is an enzyme that hydrolyzes phosphatidylcholine to phosphatidic acid (PA) which can then be converted to diacylglycerol (DAG) by lipin-1. However, it is unclear which of the two lipid signals, PA or DAG, underlies PLD’s mediation of aldosterone production. We hypothesized that the S1P1 receptor (S1PR1) agonist, SEW2871, (and VLDL) induces steroidogenesis and therefore aldosterone production via lipin-1-mediated metabolism of PA to DAG, with our hypothesis focusing on DAG as the key lipid signal produced by PLD (indirectly). In HAC15 cells, lipin-1 was overexpressed using an adenovirus or inhibited using propranolol followed by treatment with or without SEW2871 (or VLDL) for 24 h. Steroidogenic gene expression and aldosterone levels were monitored by qRT-PCR and radioimmunoassay, respectively. We demonstrated that lipin-1 overexpression (OE) enhanced the SEW2871-stimulated 109-fold increase in CYP11B2 expression by 26% while lipin-1 inhibition decreased the SEW2871-stimulated 56-fold increase in CYP11B2 expression by 74%. While lipin-1 OE had no further effect, propranolol reduced SEW2871-stimulated increases in NR4A1 (2-fold) and NR4A2 (9-fold) mRNA levels by 22% and 52% respectively. The SEW2871-stimulated increase in aldosterone production was inhibited by propranolol (53%), although it was not enhanced by lipin-1 OE. Similar results were obtained with VLDL. Our results are, therefore, suggestive of DAG being the key lipid signal since regulating lipin-1 affects S1PR1 agonist- and VLDL-stimulated steroidogenic gene expression and ultimately, aldosterone production. Our study warrants further investigation into these steroidogenic signaling pathways which can lead to the identification of novel therapeutic targets such as lipin-1, or its downstream pathways, to potentially treat obesity-associated hypertension.
First record of Rilipertus Haeselbarth (Hymenoptera: Braconidae: Euphorinae) from China with description of a new species
Authors: LI JUN , ZHENG MIN-LIN , CHEN JIA-HUA
Published: September 2020

Euphorinae (Hymenoptera, Braconidae) is a large subfamily of endoparasitoid wasps with 1,270+ described species worldwide (Yu et al. 2016). In the phylogenetic analysis of Stigenberg et al. (2015) Rilipertus Haeselbarth, 1996 was recovered within the tribe Perilitini Forster,1862 together with several other genera. Rilipertus is morphologically similar to Microctonus Wesmael, 1836 and Perilitus Nees, 1819 by the type of wing venation, structure of propodeum, and shape and structure of first metasomal tergite. However, Rilipertus differs distinctly from them by having shorter and conspicuously broadened ovipositor sheaths and the sculpture of the first tergite is reduced. Six species of Rilipertus are currently known (Yu et al. 2016).
Description and ontogeny of Pattersoncypris minima sp. nov. (Crustacea: Ostracoda), Araripe Basin, Northeast Brazil
Authors: DE ALMEIDA-LIMA DÉBORA SOARES , PIOVESAN ENELISE KATIA , SAYÃO JULIANA MANSO , DE LIMA FLAVIANA JORGE
Published: September 2020

Representatives of the Class Ostracoda are widely used as tools in applied paleoecological and biostratigraphical studies in all continents. In the Araripe Basin, located in the northeastern of Brazil, the Romualdo Formation is one of the most studied, not only for the preservation but also for the abundance of its fossils. The ostracod genus Pattersoncypris Bate, 1972 is well-represented in this formation and it is the most abundant, which reinforces the importance of its taxonomic study. In this work, Pattersoncypris minima sp. nov. is described for the Romualdo Formation as a contribution to the knowledge on Brazilian Cretaceous non-marine ostracods. Taphonomic aspects are also presented, considering the complete ontogenetic stages of the material.
Studying Scale Dependency of Aerosol–Cloud Interactions Using Multiscale Cloud Formulations
Authors: Glotfelty Timothy , Alapaty Kiran , He Jian , Hawbecker Patrick , Song Xiaoliang , Zhang Guang
Published: September 2020

The Weather Research and Forecasting Model with Aerosol–Cloud Interactions (WRF-ACI) configuration is used to investigate the scale dependency of aerosol–cloud interactions (ACI) across the “gray zone” scales for grid-scale and subgrid-scale clouds. The impacts of ACI on weather are examined across regions in the eastern and western United States at 36, 12, 4, and 1 km grid spacing for short-term periods during the summer of 2006. ACI impacts are determined by comparing simulations with current climatological aerosol levels to simulations with aerosol levels reduced by 90%. The aerosol–cloud lifetime effect is found to be the dominant process leading to suppressed precipitation in regions of the eastern United States, while regions in the western United States experience offsetting impacts on precipitation from the cloud lifetime effect and other effects that enhance precipitation. Generally, the cloud lifetime effect weakens with decreasing grid spacing due to a decrease in relative importance of autoconversion compared to accretion. Subgrid-scale ACI are dominant at 36 km, while grid-scale ACI are dominant at 4 and 1 km. At 12 km grid spacing, grid-scale and subgrid-scale ACI processes are comparable in magnitude and spatial coverage, but random perturbations in grid-scale ACI impacts make the overall grid-scale ACI impact appear muted. This competing behavior of grid- and subgrid-scale clouds complicate the understanding of ACI at 12 km within the current WRF modeling framework. The work implies including subgrid-scale cloud microphysics and ice/mixed-phase-cloud ACI processes may be necessary in weather and climate models to study ACI effectively.
Le numérisme : un objet religieux ? Problématisation et notes théoriques
Authors: Perreault Jean-Philippe , Vaillancourt Martin
Published: September 2020

For the most part, studies on the relationship between religion and digital can be grouped under the theme Digital Religion. Without being totally foreign to it, the phenomenon we are interested in here seems to be of a different order. Rather than ‘digitized religion’, we are confronted with what we might understand as a quest for digital meaning. Some authors who have described this technological religiosity argue that it serves to legitimize the belief in a new society. The study of what we have called ‘digitization’ would therefore be based on the sacralization of a set of techno-values, of which the internet would be both the tool of broadcast and the main symbolic object. If we recognize that religion has something to do with society’s idea of itself, we can ask ourselves whether the digital revolution, by generating a new type of society, does not contain a religious dimension.
Chronic pulmonary thromboembolism due to intracardiac and pulmonary hydatidosis
Authors: Kaskar Ameya , Shetty Varun , Shetty Devi
Published: September 2020

Hydatid disease remains a problem in endemic areas. The combination of both intracardiac and pulmonary hydatid disease in association with chronic pulmonary thromboembolism is a rare presentation. We report a case of a 14-year-old girl with hydatid disease of the lungs, right ventricle, and pulmonary arteries, presenting as chronic pulmonary thromboembolism. She underwent surgery for wedge resection of the pulmonary hydatid in the right lower lobe, removal of the right ventricular hydatid (under cardiopulmonary bypass), and pulmonary endarterectomy (under total circulatory arrest). Her postoperative recovery was uneventful.
Concentration polarization phenomenon in new and re-used RP610 hemofilters during post-dilutional hemofiltration
Authors: Andreucci V.E. , Calderaro V. , Memoli B. , Terracciano V. , Caputo A. , Bazzicalupo L. , Salvatore M.
Published: September 2020

RP610 hemofilters have been used up to five times in Post-dilutional hemofiltration. Clearance studies were Performed «in vivo» (creatinine and phosphate) and «in vitro» (Cr51 EDTA, I131 Hypaque, Co57 vitamin B12, H3 Inulin, C14 Dextran, l125 Albumin,) in new hemofilters and in those re-used once and five times. Hydraulic permeability and rejection coefficients, for the six markers different molecular weight, were also measured. Our preliminary results show that repeated cleansing with Amuchina® does not alter the characteristics of RP610 hemofilters. A scintigraphic method is suggested for visualizing possible changes in polarized areas between new and re-used hemofilters.
WE43 and WE43-T5 Mg alloys screws tested in-vitro cellular adhesion and differentiation assay and in-vivo histomorphologic analysis in an ovine model
Authors: Torroni Andrea , Witek Lukasz , Fahliogullari Hayat Pelin , Bortoli Joao Paulo , Ibrahim Amel , Hacquebord Jacques , Gupta Nikhil , Coelho Paulo
Published: September 2020

WE43 Mg alloy proved to be an ideal candidate for production of resorbable implants in both clinical and trial settings. In previous studies we tested biocompatibility and degradation properties of WE43 (as-cast) and artificially aged (WE43-T5) Mg alloys in a sheep model. Both alloys showed excellent biocompatibility with the as-cast, WE43, form showing increased degradability compared to the artificially aged, WE43-T5. In the present study, our group assessed the biological behavior and degradation pattern of the same alloys when implanted as endosteal implants in a sheep model. Twelve screws (3x15 mm) were evaluated, one screw per each composition was placed bi-cortically in the mandible of each animal with a titanium (2x12 mm) screw serving as an internal positive control. At 6 and 24 weeks histomorphological analysis was performed, at 6 weeks as cast, WE43, yielded a higher degradation rate, increased bone remodeling and osteolysis compared to the WE43-T5 alloy; however, at 24 weeks WE43-T5 showed higher degradation rate and increased bone remodeling than as-cast. In vitro assay of cell growth, adhesion and differentiation was also conducted to investigate possible mechanisms underlying the behavior expressed from the alloys in vivo. In conclusion WE43-T5 indicated bone/implant interaction properties that makes it more suitable for fabrication of endosteal bone screws.
Analysis and directions of OEE and its integration with different strategic tools
Authors: Singh Sandeep , Khamba Jaimal Singh , Singh Davinder
Published: September 2020

The manufacturing industries are among the focused industries of any country according to their contribution to nations’ economies. Therefore, the appropriate utilization of all manufacturing/processing equipment is a high priority. The problem is the complexity to keep all the activities, operations, and use of equipment in synchronization with the reduction of all possible losses and defects. Such losses are becoming the real cause of the investment in the maintenance section of the industrial units. The different versions of established concepts define ‘Maintenance’ as ‘repair of the equipment,’ but this concept covers old and limited dimensions. Therefore, this notion relates the maintenance strategies only as a function of preventive maintenance, predictive maintenance and corrective maintenance. At the basic level of OEE implementation, various process industries of the country are yet unaware of the potential benefits of this strategic tool. The quality and performance-enhancing approaches are being developed based on time management and production loss analysis to get the optimum output from available resources. This study is to mark all the critical strategies associated with sustainable performance and to trace all possible drawbacks while measuring effectiveness through OEE (Overall Equipment Effectiveness). OEE is a tool of Total Productive Maintenance (TPM) without whom the effective utilization of resources is a difficult task. OEE supports the entire perspective on effectiveness uniquely and logically but also improves the life span of the machinery through improvements and monitoring in the maintenance operations and activities. This paper aims to identify the role of different strategies associated with OEE for unceasable production and optimum use of resources. This paper arranges the literature in an organized way and assists to find promising decisions to implement OEE with integrated concepts.
Experimental investigation of non-premixed and partially premixed methane lifted flames established on a lobed swirl injector
Authors: Jiang Lei , Li Gang , Jiang Xi , Hu Hongbin , Xiao Bo , Xu Yanji , Lei Zhijun
Published: September 2020

A lobed swirl injector was tested to examine its potential in combustion control for non-premixed and partially premixed flames. It was found in the experiment that the flame derived from the injector changed between attached and detached flames at different conditions, demonstrating a promising way to control combustion. When air is supplied through the external channel of the lobed swirl injector and fuel passes through the internal channel, a stable lifted flame that is partially premixed was established above the injector exit. With the increase of airflow rate, the flame lift-off height decreases gradually until it is reattached to the injector, forming a diffusion flame. When increasing the fuel flow rate, the lift-off height increases gradually until the flame is blown out. Flow fields of the partially premixed lifted flames were investigated using stereoscopic particle image velocimetry. Streamlines located in the near field of the injector exit do not expand but bend inward, which is quite different from the expansion motion at the exit of the traditional vane swirler. The trough structure on the lobed swirler leads to the outer air flowing inward. Although the crest structure should make the inside gas flow outward, the strong entrainment of the surrounding air would restrain the radial outward motion of the inner gas, thus causing a contracted motion. After the streamline develops to an axial position further away from the injector exit, the swirling jet begins to expand under effects of both the centrifugal force and the development of shear layer to form turbulence. This flow pattern affects both the flame stabilization position and the neighboring reaction zone structure significantly. The measurements also show that the lobed swirl injector is very capable of entraining the ambient air that is sucked into the mainstream from the downward direction.
Management of oncology-related emergencies at the emergency department: A long-term undertaking
Authors: Chua Wei Lin Tallie , Chan Shi En Joanna , Lai Gillianne , Yong Looi Yee Tracy , Kanesvaran Ravindran , Anantharaman Venkataraman
Published: September 2020

Background:

The emergency department at the Singapore General Hospital is an emergency department with an annual census of 140,000 and oncology-related attendances of about 4000 (2.8%). These patients are often admitted for further care. Palliative care in the emergency department for these patients is often minimal. The aim of this study was to determine the state of current management of oncology-related emergencies at the Singapore General Hospital’s emergency department, hence identifying specific areas for intervention.

Methods:

We carried out a retrospective data review of all Singapore General Hospital’s emergency department patients who had either cancer-related diagnoses or were admitted to the Medical Oncology Department in October 2018. Simple statistical analysis was then performed using IBM SPSS version 21.

Results:

Of 308 identified patients, there was approximately equal distribution by sex. The women were generally younger than the men (61.33 ± 13.63 years vs 67.36 ± 12.02 years, p = 0.063, confidence interval −8.94 to −3.13). Seventy-two (23.4%) of the patients arrived at emergency department by ambulance. The mean emergency department length of stay was 4.25 h. About half of the patients had either lung, colorectal, or breast as their primary site of cancer. There was no correlation between clinical severity according to the National Early Warning Scores and triage complaint-type or emergency clinical diagnosis. More than 90% were admitted, with about 32.6% dying during their inpatient stay. High National Early Warning Scores were significantly associated with mortality.

Conclusion:

There is large potential for interventions to improve patient well-being in the pre-hospital setting and emergency department. Given the sizable number of patients with poor outcomes, palliative care is also of paramount importance.