bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Bacteria on Animal Metamorphosis
Authors: Cavalcanti Giselle S. , Alker Amanda T. , Delherbe Nathalie , Malter Kyle E. , Shikuma Nicholas J.
Published: September 2020

The swimming larvae of many marine animals identify a location on the seafloor to settle and undergo metamorphosis based on the presence of specific surface-bound bacteria. While bacteria-stimulated metamorphosis underpins processes such as the fouling of ship hulls, animal development in aquaculture, and the recruitment of new animals to coral reef ecosystems, little is known about the mechanisms governing this microbe-animal interaction. Here we review what is known and what we hope to learn about how bacteria and the factors they produce stimulate animal metamorphosis. With a few emerging model systems, including the tubeworm Hydroides elegans, corals, and the hydrozoan Hydractinia, we have begun to identify bacterial cues that stimulate animal metamorphosis and test hypotheses addressing their mechanisms of action. By understanding the mechanisms by which bacteria promote animal metamorphosis, we begin to illustrate how, and explore why, the developmental decision of metamorphosis relies on cues from environmental bacteria.
Ape Origins of Human Malaria
Authors: Sharp Paul M. , Plenderleith Lindsey J. , Hahn Beatrice H.
Published: September 2020

African apes harbor at least twelve Plasmodium species, some of which have been a source of human infection. It is now well established that Plasmodium falciparum emerged following the transmission of a gorilla parasite, perhaps within the last 10,000 years, while Plasmodium vivax emerged earlier from a parasite lineage that infected humans and apes in Africa before the Duffy-negative mutation eliminated the parasite from humans there. Compared to their ape relatives, both human parasites have greatly reduced genetic diversity and an excess of nonsynonymous mutations, consistent with severe genetic bottlenecks followed by rapid population expansion. A putative new Plasmodium species widespread in chimpanzees, gorillas, and bonobos places the origin of Plasmodium malariae in Africa. Here, we review what is known about the origins and evolutionary history of all human-infective Plasmodium species, the time and circumstances of their emergence, and the diversity, host specificity, and zoonotic potential of their ape counterparts.
Influence of Plantain Pseudostem Fibres and Lime on the Properties of Cement Mortar
Authors: Danso Humphrey
Published: September 2020

This study investigated the properties of cement mortar with lime reinforced with plantain pseudostem fibres. Experimental specimens with 0, 0.25, 0.5, 0.75, and 1% fibre contents by weight of sand and 10% lime content by weight of cement were prepared and tested on 7, 14, 21, and 28 days of curing for density, tensile strength, compressive strength, SEM, and EDS. The 0.25% plantain pseudostem fibre reinforced mortar achieved 23.4% compressive strength improvement over unreinforced mortar specimens. There was between 6.89 and 13.80% increase in tensile strength of the plantain pseudostem fibre reinforced mortar over the unreinforced mortar specimens. A positive linear correlation was found between the compressive strength and tensile strength of cement mortar reinforced with plantain pseudostem fibres and lime with coefficient of determinant (R2) values between 0.909 and 0.869. It was also observed that the plantain pseudostem fibre reinforced mortar specimen had some microcracks and voids from the SEM analysis. Furthermore, EDS analysis showed the presence of calcium silicate hydrate with a Ca/Si ratio of between 1.02 and 2.49, and Al/Si ratio of between 0.76 and 0.81 as the main oxide. It therefore concluded that the incorporation of plantain pseudostem fibre and lime positively influenced the properties of the cement mortar with the 0.25% fibre content being recommended for construction application.
Expanding our Understanding of Atypical Antipsychotics: Acute Urinary Retention Secondary to Olanzapine
Authors: Mirzakhani Hannah , Rahim Mariam , Mathew Jacob
Published: September 2020

Antipsychotics are considered the most efficacious drugs in the treatment of schizophrenia and other psychotic disorders. While clinicians monitor for the onset of extrapyramidal symptoms (EPSs), many do not consider the antimuscarinic and histaminergic side effects that can occur with second generation antipsychotics. We present the case of a 62-year-old male who presented with acute urinary retention that was found to be due to the recent initiation of olanzapine. Gradual cessation of the medication and follow-up with urology revealed resolution of his symptoms. With the increasing demand for psychiatric care but limited psychiatric resources, more and more primary care physicians find themselves dealing with the complex challenges of mental illness and managing antipsychotic medications. As a result, coordinating care among multiple specialties and understanding the full profile of side effects that are associated with psychiatric medications can yield quicker diagnoses and improve patient care.
Influence of Various Chemical Surface Treatments, Repair Materials, and Techniques on Transverse Strength of Thermoplastic Nylon Denture Base
Authors: Naji Ghassan Abdul-Hamid
Published: September 2020

The process of repairing the fractured nylon denture bases and addition of acrylic teeth to the previously worn nylon denture bases has not been widely studied. This study aims to assess the transverse strength of nylon denture bases repaired by various resin materials, different curing techniques, and types of surface treatments. Materials and Methods. One hundred fifty thermoplastic nylon denture base samples were fabricated using plastic patterns measuring 65 × 10 × 2.5 mm (length, width, and thickness, respectively). These samples were then divided into three equal groups. Fifty samples were repaired by microwave heat-polymerization, fifty samples were repaired using the Ivomate autopolymerization, and the other fifty were repaired using light-polymerized acrylic resin. Each of these three groups was further divided into five subgroups of ten samples based on the type of surface treatment. The samples in the control group did not undergo any surface treatment, and the other four groups were chemically surface treated with monomer, acetone, ethyl acetate, and isopropanol, respectively. A three-point bending test was used to calculate the transverse strength values of the samples. Fourier transform infrared (FTIR) analysis was conducted to determine the component of functional groups between the polyamide nylon base and poly(methyl-methacrylate) PMMA repair materials. A polarizing microscope was utilized to investigate the mode of failure at the fracture surfaces. Results. The collected data were analyzed with one-way ANOVA and Sidak’s multiple comparison test to show the differences among different groups. For surface treatments, the highest transverse strength values were obtained by monomer-treated samples (18.29 N/mm2); however, the lowest values were obtained in non-surface treated samples (5.58 N/mm2). While for repair techniques, the highest transverse strength values were obtained by microwave processing, followed by Ivomate and then the light-cured polymerization. The means were found to be significant (p<0.001). FTIR analysis shows the presence of hydrogen bonding which is due to the ester and amid groups which enhance the bond strength of the surface-treated samples. The interface of the polarizing microscope images revealed a cohesive fracture within repair materials rather than the adhesive nature. Conclusion. The microwave-polymerized resin was considered as the most effective repair technique along with monomer chemical etchant which creates a tight adhesion between PMMA and nylon denture base in comparison to other groups.
Seismic Performance Analysis of Self-Centering Concentrically Braced Steel Frame Structures
Authors: Xiong Ergang , Zu Kun , Zhang Qian
Published: September 2020

To study the seismic performance of self-centering concentrically braced frame (SC-CBF) structure, the static elastoplastic analysis, low-cycle repeated loading analysis, and elastoplastic time-history analysis were conducted for a four-story SC-CBF structure, compared with the traditionally concentrically braced frame (CBF) structure. The influences of different GAP stiffnesses and cross-sectional areas of prestressed tendon were investigated on the self-centering and seismic performance of the SC-CBF structure. The results show that the SC-CBF structure has a strong lateral resistance, a small base shear under earthquake action, and a slight residual drift after unloading. The SC-CBF structure has a better ductility than the CBF structure. The displacement of the SC-CBF structure under the action of rare and extremely rare earthquakes is large, and the structure can dissipate more energy; the interstory drift is large, but the residual drift is small, exhibiting its ideal seismic and self-centering performance. However, the mechanical behavior of prestressed tendons is significantly affected by the stiffness of the GAP. The mechanical and seismic performances of the overall structure are slightly affected by the stiffness of the GAP, but the cross-sectional area of the prestressed tendons has a remarkable influence on the overall performance of the structure.
Abstract 13: Cholic Acid Supplementation Attenuates Hypertension In Spontaneously Hypertensive Stroke Prone Rats
Authors: Zhang Bojun , Ayyaswamy Sriram , Bryan Robert M , Durgan David J
Published: September 2020

Recent studies have demonstrated a causal role of gut dysbiosis in the development of hypertension in several animal models. However, our understanding of the mechanisms linking gut dysbiosis to blood pressure (BP) regulation of the host is still lacking. One key mechanism by which the microbiota influences the host is through the generation/modification of metabolites, such as bile acids (BAs). BA signaling has been shown to influence many pathways involved in BP regulation, including systemic inflammation and vascular function. We previously observed that spontaneously hypertensive stroke prone rat (SHRSP) exhibited dysbiotic cecal microbiome, which included a significant increase in the genus
Lactobacillus
, known to sequester BAs within its cytosol and reduce BAs availability, when compared to WKY. Thus, we hypothesized that
gut dysbiosis contributes to the development of hypertension by reducing bile acid signaling.
We observed a significant reduction in 9 of 18 plasma BAs in SHRSPs, as compared to WKY. This included a 72% reduction in cholic acid (CA), a primary BA (n=7-8, p<0.05). We next examined the effects of CA supplementation (0.5% CA diet for 16 weeks) on systolic BP (SBP) in WKY and SHRSP. Within the 9 BAs that were reduced in SHRSP, CA and hyocholic acid were restored by CA treatment in SHRSP plasma to similar levels of that observed in WKY control plasma. Furthermore, CA treatment decreased SBP by 18 ±7mmHg at 20 weeks in SHRSP (n=7-8, p<0.05), but had no effect on SBP in WKY rats. Acetylcholine-induced vasodilation of the aorta was significantly impaired in SHRSP control by 40% (10
-6
μM ACh, 59.5% vs. 99.3%) as compared to WKY control (n=3-4, p<0.01). CA treatment significantly improved endothelium-dependent vasodilation in the aorta of SHRSP rats similar to that in WKY rats (n=3-4, p<0.05). CA treatment also altered a number of bacteria in the gut including restoration of relative abundance of
Lactobacillus
in SHRSP to the level of WKY controls. We conclude that reduced BA signaling contributes to the development of hypertension in SHRSP, and that CA treatment may be a potential therapeutic approach to attenuate vascular endothelial dysfunction and associated hypertension.
Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response
Authors: Xue Baojian , Beltz Terry , Guo Fang , Pollock David M , Pollock Jennifer S , Johnson Alan K
Published: September 2020

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.
Abstract 2: Increased Complement Regulator CD55 Is Associated With A Reduction In Pancreatic Beta Cell Area In Islets Of Rat Offspring Following Chronic Placental Ischemia-induced Hypertension
Authors: Regal Jean F , Root Kate M , Towner Kendra J , Akhaphong Brian U , Alejandro Emilyn U
Published: September 2020

Placental insufficiency can result in gestational hypertension and/or intrauterine growth restriction (IUGR) in the offspring. Gestational hypertension with or without low birth weight is associated with increased risk for Type 2 diabetes in the offspring. Pancreatic β cell mass, set very early in life, can influence whether an individual develops Type 2 diabetes. Our previous studies demonstrated a significant reduction in β cell area in embryonic day 19 and postnatal day (PD)13 female offspring of rats subjected to chronic placental ischemia-induced hypertension. Previous studies in human islets demonstrated important roles for complement C3 and activation product C3a in determining β cell area, with increased C3a generation associated with prevention of islet cell atrophy. Thus, we hypothesized that increases in self-proteins that limit complement system activation, i.e. complement regulators, are associated with reductions in β cell area in the offspring following placental insufficiency. The Reduced Uterine Perfusion Pressure (RUPP) model was used to induce placental insufficiency in the dam by placing silver clips on the abdominal aorta and uterine arteries on gestation day 14 of a 21 day gestation to mechanically reduce placental perfusion. This results in hypertension in the dam and IUGR in the offspring. Islets from the pancreas of (PD)13 female offspring of RUPP and Sham dams were isolated by collagenase perfusion and hand picking. The transcript message for complement regulators CD55 and Crry (regulators of C3 activation) and CD59 (terminal pathway regulator) was determined using qRT-PCR. Complement regulator CD55 was significantly increased in female RUPP offspring (2.01 + 0.29 fold) compared to female Sham offspring (1.00 + 0.13 fold change; p < 0.05; 6-13 pups from 4-7 dams; mixed model ANOVA including litter effect), whereas the Crry increase of 1.38 + 0.20 fold in female RUPP vs Sham offspring was not significant (p = 0.22). No significant change was observed in message for CD59 or C3. Thus, these data suggest increased islet complement regulator CD55 may limit complement activation in islets of PD13 offspring following placental ischemia and thereby contribute to reduction of β cell area and long term susceptibility for Type 2 diabetes.
Abstract 21: Telemedicine And The Barbershop Model Of Hypertension Care For Black Men
Authors: Blyler Ciantel A , Rashid Mohamad , Moy Norma B , Kemp Kayslee A , Rader Florian
Published: September 2020

Background:
The Los Angeles Barbershop Blood Pressure Study (LABBPS) demonstrated both efficacy and sustainability of a new model of hypertension (HTN) care for non-Hispanic black men that links health promotion by barbers to medication management by specialty-trained pharmacists. Barriers to scaling the model include logistical inefficiencies that contribute to the cost of the intervention. Most notable was the amount of time pharmacists spent traveling between barbershops. To address this, we tested whether telemedicine (remote follow-up) could be substituted for in-person visits after blood pressure (BP) control was achieved.

Methods:
We enrolled 10 black male patrons with systolic BP ≥ 140 mm Hg in this proof-of-concept study in which barbers promoted follow-up with pharmacists who initially met each patron in the barbershop where they prescribed BP medication under a collaborative practice agreement with the patrons’ physician. Medications were titrated during bimonthly in-person visits to achieve a BP goal of ≤130/80 mmHg. Once BP goal was reached, monthly visits were done by videoconference while barbers assisted with BP checks. Final BP and safety outcomes were assessed at 12 months.

Results:
After exclusion of one participant who declined adherence, 9 patients completed the intervention. Baseline BP of 155
+
14 / 83
+
11 mmHg decreased by 29
+
13 / 8.9
+
15 mmHg (p<.0001), with eight participants (89%) achieving systolic control and seven (78%) diastolic control at 12 months. These new data are statistically indistinguishable from our previous LABBPS data (p=0.8 for both change in systolic BP and diastolic BP). Overall HTN control (≤ 130/80) was 67% (6 of 9), numerically greater than the 63% observed in LABBPS (p=N.S.). As intended, the mean number of in-person pharmacist visits per patron fell from 11 in LABBPS to 6.6 visits over 12 months. No treatment-related serious adverse events occurred. Cohort retention was 90%.

Conclusions:
Telemedicine represents a viable substitute for in-person visits, both improving pharmacist efficiency and reducing cost while preserving intervention potency. These findings are crucial for future broad-scale implementation efforts and development of cost-effective barbershop HTN management programs for black men.
Abstract 6: Comparison Between Ambulatory BP Percentile And Load As Predictors Of Target Organ Damage In Youth
Authors: Hamdani Gilad , Ferguson Michael A , Lande Marc B , Meyers Kevin , Mitsnefes Mark , Samuels Joshua A , Flynn Joseph T , Urbina Elaine M
Published: September 2020

Ambulatory BP (ABP) is increasingly used to confirm the diagnosis of hypertension. Pediatric but not adult guidelines consider BP load (% readings above 95
th
%ile) in risk-stratification of the ABP phenotype. We compared ABP sex- and height- specific percentile and BP load as predictors of left ventricular hypertrophy (LVH) in youth. We measured casual BP, ABP, anthropometrics, and calculated LV mass by echo as (g)/height (m)
2.7
(LVMI) in 357 adolescents (mean age 15.5
+
1.7 years, 63% white, 59% male). ABPM was performed with the Ontrak device (Spacelabs Inc., Snoqualmie, WA). ABP index was defined as mean ABP/sex- and height-specific 95
th
%ile. LVH was defined as LVMI ≥38.6 (pediatric cut-point). Logistic regression was used to assess different ABP measures as predictors of LVH. Sensitivity and specificity of different ABP cut points as predictors of LVH were calculated. Seventy (19.6%) participants had LVH. Systolic 24-hour, wake and sleep ABP indices as well as 24-hour SBP load were all significantly associated with LVH, while wake and sleep SBP load were not. When adjusted for BMI percentile and sex, only the associations between ABP indices and LVH remained statistically significant (table). SBP percentiles also had better balanced sensitivities and specificities in predicting LVH (24-hour 65
th
percentile: 63% and 59%; wake 70
th
percentile: 54% and 62%; sleep 75
th
percentile: 60% and 61%). There was no significant association between diastolic BP measures and LVH. We conclude that there is no significant contribution of BP load in predicting LVH in youth. Systolic ABP percentiles lower than the commonly used 95
th
percentile are the best predictors of LVH in this population.
Abstract MP12: Increasing Circulating Anp Levels With Sacubitril Without Ras Blockage Aggravates Renal Disease In Dahl Ss Rats
Authors: Sarsenova Elizaveta , Polina Iuliia , Domondon Mark , Schibalski Ryan , Sultanova Regina , Ilatovskaya Daria
Published: September 2020

Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from high salt intake can be partially associated with a lower level of the atrial natriuretic peptide (ANP). In plasma, ANP is quickly degraded by neprilysin; therefore, pharmacological inhibition of this metalloprotease (f.i. with sacubitril) can increase ANP level. We have shown earlier that lower dose of sacubitril in combination with valsartan (75 μg/day) has beneficial effects on renal function in SS hypertension. The goal of this study was to evaluate the effects of sacubitril administered at a higher dose on renal damage of Dahl SS rats. Sacubitril (125 μg/day) or vehicle were administered to male Dahl SS rats (Charles River) via s.c. osmotic pumps. To induce hypertension, both groups were fed a purified 4% NaCl diet (HS, Dyets Inc) for 21 days. Glomerular filtration rate (GFR, FITC-inulin) and BP (tail cuff) values were obtained before and after the HS challenge. Data was analyzed with 1-way ANOVA. When compared to vehicle treated rats, 125 μg/day of sacubitril insignificantly increased systolic BP measured at the end of the 21-day HS challenge; no changes in GFR, heart weight, plasma electrolytes, BUN and creatinine were observed. However, sacubitril caused kidney hypertrophy (two kidneys to body weight: 8.8±0.4 vs 10.4±0.4 mg/g, p=0.04,), but did not affect renal medullary of cortical fibrosis. We also observed aggravated glomerular lesions in the sacubitril-treated animals compared to controls (glomerular injury score: 1.6±0.02 vs 0.9±0.08 au, p=0.034), and increased formation of protein casts (1.8±0.3 vs 1.3±0.2 au, p=0.034). Thus, in Dahl SS rats, administration of sacubitril at 125 μg/day had adverse effects on renal disease progression, especially glomerular damage and protein casts formation. In our prior study we showed that the combination of sacubitril at 75 μg/day with the angiotensin receptor blocker (ARB), valsartan, is effective to alleviate these outcomes. It is likely that the inhibition of neprilysin by sacubitril results in accumulation of Ang II and/or bradykinin and/or RAAS activation, which masks the beneficial effects of ANP level increase.
Abstract MP29: Activation Of Transient Receptor Potential Melastatin 2 (trpm2) Cation Channel Contributes To Nox4-induced Protective Effects In Endothelial Cells.
Authors: Alves-Lopes Rheure , Neves Karla B , Harvey Adam , Montezano Augusto C , Touyz Rhian M
Published: September 2020

NOX4-induced H
2
O
2
production promotes vasodilation and is cardiovascular protective. H
2
O
2
also regulates TRPM2, a redox-sensitive channel that regulates Ca
2
influx. eNOS is a Ca
2+
-dependent enzyme, and hypertension-associated endothelial dysfunction involves eNOS inactivation. As NOX4-derived H
2
O
2
regulates TRPM2 and consequently Ca
2+
influx, we questioned whether downregulation of the H
2
O
2
-TRPM2-Ca
2+
axis in endothelial cells may contributes to impaired vascular relaxation in hypertension. WT and TTRhRen hypertensive mice were crossed with Nox4 KO mice. Vascular function was studied in mesenteric resistance arteries by wire myography. Ca
2+
influx was assessed by fluorescence microscopy in aortic endothelial cells, eNOS activation and TRPM2 expression were assessed by immunoblotting and immunohistochemistry, respectively. Blood pressure in TTRhRen (130.3±7.0 mmHg) and TTRhRen/NOX4 KO mice (141.3±18 mmHg) was significantly increased compared to control mice (98.1±8.0 mmHg). Endothelium-dependent relaxation was impaired in TTRhRen mice (Emax: WT 83.5±4.03
vs
TTRhRen 59.1±3.5), effects worsened by NOX4 KO (37.9±5.4), p<0.05. Activation of TRPM2 with ADPR, improved vascular relaxation in TTRhRen/NOX4 KO mice (75.9±7.7); an effect also achieved with H
2
O
2
incubation (74.2±15.4), p<0.05. Ang II stimulated H
2
O
2
generation (% of control: 138.23±9.04) followed by Ca
2+
influx (AUC - Ca
2+
: 19401.25±1940.21), an important regulator of eNOS. These processes were reduced by TRPM2 inhibition (AUC - Ca
2+
: 8-br-cADPR 15232.2±1052.0; Olaparib 14260±843.2 and 2-APB 13095.2±277.4, p<0.05) and by the NOX1/4 inhibitor GKT137831 (AUC - Ca
2+
: Ang II 107357±1940.2 vs GKT 15067.5±255.6, p<0.05). Activation of eNOS (Ser1177) by Ang II in endothelial cells was blocked by PEG-catalase, GKT137831, and the TRPM2 inhibitor 8-br-cADPR. TRPM2 inhibitors also increased MAPK expression in endothelial cells. In conclusion, endothelial dysfunction in TTRhRen/NOX4 KO mice involves impaired TRPM2 activation. Reduced bioavailability of H
2
O
2
due to Nox4 downregulation is a major driver of this process. We identify a new axis in endothelial cells involving Nox4-H
2
O
2
-mediated activation of TRPM2-Ca
2+
-eNOS signalling which is vasoprotective.
Abstract MP34: Association Between Leg Adiposity And Hypertension Subtype In Young And Middle-aged Adults
Authors: Visaria Aayush , Lo David , Maniar Pranay
Published: September 2020

Objective:
We sought to determine whether leg adiposity was inversely associated with hypertension using the 2011-2016 National Health & Nutrition Examination Surveys.

Methods:
The study included 5,997 non-pregnant adults aged 20-59 who were not taking antihypertensives and did not have self-reported history of cardiovascular disease. Leg adiposity was defined as the percent of total fat mass present in bilateral lower extremities as per dual-energy x-ray absorptiometry (DXA) scans. Leg adiposity was then categorized into two sex-specific groups (low fat %: <34 for male, <39 for female; high fat %: ≥34 for male, ≥39 for female). The outcome was hypertension subtype. Hypertension was defined as BP >130/80, and subtypes included isolated diastolic hypertension (IDH), isolated systolic hypertension (ISH), and systo-diastolic hypertension (SDH). We estimated relative risk ratios (RRR) using multinomial logistic regression, adjusting for covariates (see
Table 1
) and accounting for the complex survey design.

Results:
Among the 5,997 participants, 2,945 (49%) were female, the average (SD) age was 37.4 (0.3) years, and 1,465 (24%) had hypertension. Those with higher leg fat had 53%, 39%, and 61% lower unadjusted relative odds of IDH, ISH, and SDH, respectively (
Table 1
). After adjustment, those with higher leg fat had 31%, 24%, and 34% lower relative odds of IDH, ISH, and SDH, respectively. When treating leg adiposity as a continuous variable, higher leg adiposity reduced relative odds of SDH significantly more than ISH (
Table 1
).

Conclusion:
A greater proportional distribution of fat around the legs is inversely, independently associated with all hypertension subtypes.
Abstract MP37: Adverse Childhood Experiences Impact Blood Pressure And Pulse Wave Velocity In Adolescence
Authors: Kellum Cailin E , Kemp Keri M , Perry Paige , Mrug Sylvie , Pollock Jennifer , Seifert Michael , Feig Daniel
Published: September 2020

Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, have been associated with increased risk of cardiovascular disease (CVD) in adulthood. Understanding how ACEs affects blood pressure during early life is key for the development of early interventions that may reduce the risk of future CVD. We hypothesized that exposure to ACEs is associated with detrimental hemodynamic parameters during adolescence. This study included 78 male and female adolescents (median age=16, range=13-18) recruited from Children’s of Alabama hospital. Exclusion criteria included cardiovascular or renal disease and antihypertensive medication. An oscillometric blood pressure (BP) monitor was used to measure 24-h ambulatory BP. ACE exposure was measured with the Adolescent Life Change Event (ALCES) questionnaire and was prevalent, with 65% (51 of 78) of participants experiencing 1 ACEs. The mean cumulative ACE score was 1.4±0.2. ACE exposure was not correlated with gender, race, age, or body mass index (BMI). Linear regression models were utilized to link ACE exposure (0 versus 1 ACEs) with 24-h mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and pulse wave velocity (PWV). Race and gender were included as covariates. Mean 24-h DBP was significantly (p=0.04) higher in participants with ACE exposure (65.9±0.7 mmHg, n=51) compared to those with no ACE exposure (64.1±0.9 mmHg, n=27); this association was independent of covariates. Since BMI was significantly correlated with SBP, PWV, and MAP, additional models included BMI as a covariate. Both ACE exposure (p= 0.02) and BMI (p<0.001) were associated with increased PWV, while the interaction between ACE exposure and BMI was negatively associated with PWV (p=0.02). Mean 24-h SBP and MAP were not significantly associated with ACE exposure. The finding that ACE exposure is associated with elevated DBP and PWV and not with SBP is in accordance with previously reported results in young adults and suggests that ACEs may alter autonomic pathways leading to CVD and hypertension. Interventions targeted at individuals with ACE exposure early in life could lower the risk of arterial stiffness and in turn the cascade of events leading to CVD.
Abstract MP38: High Salt Activates The NLRP3 Inflammasome In Antigen Presenting Cells Via ENaC To Promote Salt-Sensitive Hypertension
Authors: Pitzer Ashley L , Barbaro Natalia R , Aden Luul , Ray Evan C , Kleyman Thomas R , Kirabo Annet
Published: September 2020

Salt-sensitivity is a major risk factor for hypertension and cardiovascular disease (CVD). Reducing dietary Na
+
decreases blood pressure and CVD risk. However, the precise mechanisms of how Na
+
leads to hypertension are still not well defined. Recently, we found that dendritic cells (DCs) in response to increases in extracellular [Na
+
] exhibit an amiloride-sensitive epithelial Na
+
channel (ENaC)-dependent activation of NADPH-oxidase, superoxide production, reactive isolevuglandin (IsoLG)-protein adduct formation, and cytokine secretion which promote hypertension. We hypothesized that the NLRP3 inflammasome in antigen-presenting cells (APCs) mediates salt-sensitive hypertension through an ENaC-dependent mechanism. To test this hypothesis, we cultured mouse splenocytes in normal-salt or high-salt (HS) media with or without co-treatment with the ENaC inhibitor, amiloride (20 μM). Using flow cytometry, we found that HS increased monocyte and DC IL-1β production, which was confirmed through an ELISA assay detecting IL-1β release (2.131 ± 0.733 vs 12.75 ± 1.108 pg/mL, p<0.01) into the culture media, and amiloride treatment prevented IL-1β production (12.75 ± 1.108 vs 1.905 ± 0.3495 pg/mL, p<0.01) in these cells. To confirm our
in vitro
data, we treated salt-sensitive mice on a 129-SvJ background with a HS diet (4% NaCl) for 28 days with or without amiloride (1mg/kg/day in drinking water) or NLRP3 inflammasome inhibitor MCC950 (10mg/kg i.p.). Amiloride or MCC950 treated mice developed blunted hypertension in response to HS (120.4 ± 2.99; 101.0 ± 3.74) compared to vehicle controls (140.5 ± 3.98). Amiloride treated mice also exhibited less expression of NLRP3, pro-IL1β, and IsoLGs in DCs and monocytes compared to controls. Interestingly, MCC950 treated mice exhibited decreased pro-IL1β but not NLRP3 expression or IsoLG production. Using the DOCA-salt model, we found similar increases in NLRP3, pro-IL1β, and IsoLGs expression in DCs and monocytes, which was abolished after treatment with IsoLG scavenger 2-HOBA (1g/L). Our findings suggest a role for ENaC-dependent NLRP3 inflammasome activation in APCs in response to a HS diet, which may represent a promising treatment approach to salt-induced hypertension.
Abstract P003: Kidney-specific Knockout Of The Clock Protein Bmal1 Is Protective In Salt-sensitive Hypertension
Authors: Crislip Gene R , Douma Lauren , Cheng Kit-Yan , Roig Emilio , Barral Dominique , Lynch I. Jeanette , Wingo Charles , Gumz Michelle L
Published: September 2020

Intro:
Circadian clock factors, such as BMAL1, influence systemic blood pressure (BP) control. Previously, we generated renal distal segment BMAL1 knockout mice (KS-BMAL1 KO) that exhibit lower BP compared to control mice (CNTL) in males but not females. Additionally, male KS-BMAL1 KO retain less sodium following potassium depletion compared to CNTL, a difference not seen in females.

Goal:
The goal of this study was to test the hypothesis that male KS-BMAL1 KO display lower BP than CNTL in response to a potassium deficient, high salt diet.

Methods:
Our mouse model was generated using floxed exon 8 BMAL1 mice crossed with kidney-specific cadherin Cre+ mice to generate KS-BMAL1 KO. Floxed Cre- littermates were used as CNTL. Male mice were implanted with telemeter devices for 24-hour BP monitoring before and during administration of a low potassium diet over 7 days (0% K, 0.2% Na) and followed by a low potassium, high salt diet for 10 days (0% K, 2% Na, N=7-8). Two-way ANOVA was used to compare diet and genotype effects.

Results:
Following potassium depletion alone, systolic BP significantly decreased in both genotypes (P<0.05). Compared to baseline, KS-BMAL KO did not exhibit the increase in BP as seen in CNT on the potassium deficient, high salt diet (CNTL: 125±2 to 132±1; KO: 123±2 to 122±2 mmHg). Neither diet nor genotype altered circadian rhythms in BP.

Conclusions:
BMAL1 in renal distal segments contributes to BP regulation. KS-BMAL1 KO appear to be protected from the substantial increase in BP that occurred in CNTL in response to a low potassium/high salt diet. These data suggest that BMAL1 contributes to the protection from salt-sensitive hypertension in the setting of a low potassium diet.
Abstract P009: Differential Redox Signaling In Urine Derived Renal Proximal Tubule Cells Isolated From Inverse Salt Sensitive Vs Salt Resistant Clinical Study Participants
Authors: Gildea John J , Daley Michael G , Xu Peng , Schiermeyer Katherine , Yue Wei , Carey Robert M , Jose Pedro A , Felder Robin
Published: September 2020

Increased morbidity and mortality occurs in some individuals consuming low sodium diets. We demonstrated that single nucleotide polymorphisms (SNPs) in the dopamine type 2 receptor (D2R) as well as lower expression of cellular and plasma membrane D2R are associated with inverse salt sensitivity (ISS, a paradoxical increase in blood pressure while on the low sodium diet). Urine derived human renal proximal tubule cells (RPTC) were cultured from 3 separate ISS and 3 salt resistant (SR, resists blood pressure change on both low and high sodium diets) participants. D2R reduces cellular redox signaling so we hypothesized that an aberrant redox state occurs in ISS and SR RPTC exposed to different NaCl concentrations. RPTC incubated in 90 mM NaCl (low salt - LS) for 2 hours in both ISS and SR RPTCs had a significant reduction of monochlorobimane (mBCl - reduced glutathione indicator) compared to 140 mM NaCl (normal salt -NS) (SR -7.1± 2.1% and ISS -9.7 ± 1.6% vs NS, n=12, p<0.05, t-test). Only ISS RPTC had a significant increase in mBCl fluorescence in 190 mM NaCl (ISS +7.0 ± 2.5% vs NS, n=12, p<0.05, t-test) and mBCl fluorescence was not affected by incubation with losartan (angiotensin type 1 receptor inhibitor). 3-Aminobenzamide (3AB, 1 mM) inhibits Parp1 (poly[ADP-ribose] synthase), a protein necessary for the transcriptional repressor CTCF insulator function. 3AB reversed the lower mBCl fluorescence only in the SR RPTC, suggesting that reducing CTCF insulator function only affects D2R wild type cells. mBCl fluorescence in ISS RPTC showed a greater reduction by LOS vs SR RPTC (ISS -49.3 ± 1.5% vs SR -37.3 ± 4.8%, n=12, p<0.05, t-test), which was blocked by nemonapride (NEM, 1 uM, D2R antagonist) and further reduced the mBCl fluorescence only in the SR RPTC. Whether these differences in salt sensitivities are due to differential effects of CTCF insulator function at the homozygous variant or wild type D2R warrants further studies.
Abstract P015: Factors Altering Luminal Succinate Effect Blood Pressure
Authors: Hering-Smith Kathleen S , Huang Weitao , Teran Fred , Sato Ryo , Hamm Lee
Published: September 2020

Luminal succinate (Suc) has been reported to activate its receptor Sucnr1, stimulate renin release and increase BP in certain contexts. NaDC1 (Na
+
dicarboxylate cotransporter), located only on apical membrane in the proximal tubule of the kidney, reabsorbs filtered citrate and Suc, and is upregulated in acidosis. NaDC1 regulation is key in preventing stones and in maintaining acid-base homeostasis; but its role in BP regulation is not known. We postulate that luminal Suc alters BP. Our purpose was to examine the role of NaDC1, luminal Suc, and acidosis in BP regulation.

To address these issues, we used NaDC1 KO (knock out) and WT (wild type) mice on normal diet or 72 hr acid diet (AD). Acidosis should lower luminal Suc due to upregulation of NaDC1 in WT mice. AD was associated with statistically significant BP decreases in both male and female WT but not in NaDC1 KO. Clearance studies compared Suc infused (SI) with non-infused NaDC1 KO and WT. ANOVA showed borderline increases between some groups: WT males on AD, BP increased from 71.48 ± 2.30 to 81.63 ± 2.16 with SI; and NaDC1 KO females on normal diet BP increased from 86.20 ± 3.98 to 96.48 ± 3.39 with SI. KO was only associated with increased BP in males on AD (p=0.05). Recently Khamaysi et al (JASN 2019) found only activity-dependent BP was altered by Suc. So, in additional studies we used telemetry (BP/T) for 24/7 monitoring of NaDC1 KO vs WT. On normal diets, mean arterial pressure (MAP) was significantly higher in KO than in WT. MAP at 9 pm: KO 122.44 ± 1.85 vs WT 110.40 ± 2.59, p <0.002, 5 am: KO 118.81 ± 2.64 vs WT 103.18 ± 4.00, p <0.01 and 8 am: KO 106.86 ± 1.28 vs 99.22 ± 2.64, p <0.02. Acidosis appeared to lessen these BP/T differences. Thus, increased luminal delivery of succinate due to KO of NaDC1 yields significant MAP increases during active periods. We examined levels of Sucnr1 in kidney cortex using droplet digital PCR (data are expressed as copy numbers of target gene in 1 ng PCR reaction). Sucnr1 expression was higher in NaDC1 KO (1343.6 ± 51) vs WT (1052.8 ± 50, p< 0.007) mice on normal diet. When fed acid diet Sucnr1 expression in KO fell (1039.6 ± 33) but increased in WT (1148 ± 50, p <0.006). In sum luminal Suc predominantly via NaDC1 reabsorption, does influence BP but this is modified by a variety of factors such as acidosis and activity.
Abstract P025: Hyperinsulinemia Causes Renal Hyperperfusion And Increases Glomerular Basement Membrane Thickness Independent Of Renal Perfusion Pressure And Glycemic Status: Potential Role Of Connecting Tubule Glomerular Feedback?
Authors: Monu Sumit R
Published: September 2020

Obesity is often associated with hyperinsulinemia (HI) and renal damage. However, the role of HI in Obesity related Renal Damage (ORD) is unclear. Renal hyperperfusion/hyperfiltration plays a major role in ORD. Normally, the kidneys autoregulate blood flow by two feedback mechanisms: 1.) Tubuloglomerular feedback (TGF), a vasoconstrictor mechanism and 2.) Connecting Tubule Glomerular Feedback (CTGF), a vasodilator mechanism. Previously, we found that Zucker obese rats had higher CTGF (TGF was unchanged) and were hyperinsulinemic before the development of ORD. Epithelial sodium channel (ENaC) initiates CTGF and Insulin is a known ENaC activator.

Hypothesis:
HI increases renal cortical blood flow (CBF) by increasing CTGF and causes renal damage. To isolate the effect of HI from the blood glucose (BG) level, HI-euglycemic clamp was created in normal anesthetized Sprague Dawley (SD) rats by simultaneous intravenous (IV) infusion of 10% glucose and insulin. Average baseline BG in non-fasted anesthetized SD rats was 199.0±31.6 mmol/L. Insulin infusion increased CBF significantly by 12.2 ± 1.3% (n=3, p<0.05) from the baseline even before the BG level starts decreasing. Insulin was further infused to attain normoglycemic condition (96.0±2.3 mmol/L) and this was associated with additional increase in CBF by 19.2 ± 4.5% (p<0.05) from the baseline. Subsequent ENaC inhibition by benzamil (BZ) (400 μg/kg, IV) completely reversed the insulin-induced increase in CBF. Neither Insulin nor BZ treatment altered the renal perfusion pressure (RPP) suggesting insulin-induced increase in CBF was independent of RPP. In a separate group of SD rats, renal-HI (1.8 IU/kg/day) was created in only one of the two kidneys for 6 weeks using renal subcapsular catheter to measure glomerular basement membrane (GBM) thickness (a marker of renal damage). GBM was significantly thickened in insulin-infused kidney compared to vehicle-infused kidney (199.4±17 vs. 145.5±3.6nm, n=3, p<0.05).

Conclusion:
Acute HI increased CBF, that was completely reversed by ENaC inhibition implying a possible role of enhanced CTGF. Chronic renal-HI caused GBM thickening.

Perspective:
HI observed in obesity or type-2 diabetes may cause renal hyperperfusion by increasing CTGF and contribute to the ORD.
Abstract P032: Dopamine Type 2 Receptor (D
2
R) Expression Modulates The Salt (NaCl) Induced Plasma Membrane Receptor Recruitment Of The Natriuretic Angiotensin Type 2 Receptor (AT
2
R) In Renal Proximal Tubule Cells Obtained From The Urine Of Salt Study Participants
Authors: Gildea John J , Xu Peng , Schiermeyer Katherine , Yue Wei , Carey Robert M , Jose Pedro A , Felder Robin A
Published: September 2020

The effect of D2R expression on the natriuretic AT2R plasma membrane recruitment in high (190 mM NaCl) and normal (140 mM NaCl) salt conditions was measured in human renal proximal tubule cells (RPTC) obtained from urine provided by salt study diet volunteers that were either salt resistant (SR) or inverse salt sensitive (ISS) (increased blood pressure on a low salt diet). Basal D2R expression was 36.9% ± 2.6% lower in ISS vs SR control n=5, p<0.01). D2R expression in the SR was reduced by siRNA (37.1% ± 2.0% reduction in ISS vs SR control, n=5, p<0.01, t-test). The ISS D2R expression was returned to normal levels by D2R overexpression using BacMam technology (22.5% ± 0.9% increase for ISS vs SR control siRNA, n=5, p<0.01, t-test). Culturing SR and ISS cell lines in normal salt (NS, 140 mM NaCl) and high salt (HS, 190 mM NaCl) leads to the recruitment of AT2R to the cell surface in the ISS cell line (ISS Control: NS 47978 ± 2728 RFU vs HS 74056 ± 3002 RFU, n=5, p<0.001, t-test), but not in the SR cell line. Knockdown of D2R using siRNA in the SR cell line altered the HS response in the SR cell line to that measured in the ISS cell line (SR D2R siRNA: NS 48514 ± 2560 RFU vs HS 82599 ± 1492 RFU, n=5, p<0.001, t-test), and the difference between SR HS control siRNA and SR HS D2R siRNA is also highly significant (SR HS: control siRNA 60154 ± 3347 RFU vs SR HS D2R siRNA 82599 ± 1492 RFU, n=5, p<0.001, t-test). Further lowering of D2R in ISS with D2R siRNA still showed a significant translocation of AT2R to the cell surface under HS (ISS D2R siRNA: NS 47953 ± 3058 RFU vs HS 80284 ± 2173 RFU, n-5, p<0.001, t-test) but not a further enhancement over SR siRNA. Overexpression of D2R in the ISS cell line completely blocked the HS AT2R cell surface recruitment, thus converting the ISS HS phenotype of ISS to a cell line that resembled a SR cell line. In conclusion, we have shown that a clear ISS phenotype of HS AT2R plasma membrane recruitment can be replicated in an SR cell line by reducing D2R expression using siRNA to levels seen in an ISS cell line. Similarly, overexpressing D2R in an ISS cell line to a level seen in SR cells reverts the ISS cells back to a SR associated sodium induced AT2R cell surface recruitment.
Abstract P037: Association Between Early Post-kidney Transplant Visit-to-Visit Systolic Blood Pressure Variability And Late Post-Transplant Systolic Blood Pressure
Authors: Tantisattamo Ekamol , Lopimpisuth Chawit , Leelaviwat Natnicha , Saowapa Sakditad , Songtanin Busara , Vutthikraivit Possawat , Polpichai Natchaya
Published: September 2020

Background:
Visit-to-visit blood pressure variability (VVBPV) results from regional or systemic circulatory factors such as stiffness or neuro-hormonal factors. Association between VVBPV and long-term post-kidney transplant (KT) blood pressure (BP) is unknown.

Method:
VVBPV was measured by average successive variability (ASV), which is the average absolute difference between successive BP measured at 4, 12, and 24 weeks post-KT. Association between the VVBPV and BP at 48 weeks post-KT was examined by multiple linear regression.

Results:
Of all 105 KT recipients, mean age±SD was 54±12 years and 64 patients (61%) was female. Mean ASV of SBP and DBP were 16±12 mmHg (range 1-58) and 11±6.3 mmHg (range 1-29.5), respectively. Mean SBP at 24 and 48 weeks post-KT were 135±19 and 133±16 mmHg, respectively. Similar to SBP, mean DBP at 24 weeks post-KT was higher than DBP at 48 weeks (DBP 24 vs 48 weeks 80±12 vs 77±11 mmHg). Every 10-mmHg increase in ASV of SBP predicts 3.4 mmHg increase in SBP at 48 weeks post-KT (p 0.01; 95%CI 0.83, 6.14; Figure 1A). However, an increase in 10 mmHg of ASV of DBP predicts a decrease in DBP of 0.12 mmHg (p 0.12, 95%CI -0.28, 0.04; Figure 1B). After adjusted for age, gender, donor type (deceased vs living), induction immunosuppressive medications, pre-KT weight-spline interaction term at 70 kg, every 10 mmHg increase in ASV of SBP was significantly associated with 2.7 mmHg increase in SBP at 48 weeks post-KT (p 0.04, 95%CI 0.15, 5.29); whereas, 10 mmHg increase in ASV of DBP predicts a decrease in DBP of 2.13 mmHg with no statistical significance (p 0.16, 95% -5.14, 0.88)

Conclusion:
Higher VVSBPV during early post-KT predicts a higher SBP, but not DBP, at late post-KT period.