bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P255: STUDY OF THE SEVERITY OF COVID-19 IN HYPERTENSIVE PATIENTS IN PRIMARY CARE, IN SPAIN. PRELIMINARY RESULTS.
Authors: Abellan-Aleman Jose , Sanchez-Macarro Maravillas , Gómez-Marcos Manuel Ángel , Crespo Rafael , García-Romanos Fernando , Valls-Roca Francisco , Fuentes Francisco , Iturralde Jesús , Velasco Ángeles , Díaz-Vera Alcibiades , Sobrino Javier , Nieto Javier , Hypertension-Covid-19 On behalf of the
Published: September 2022

Objective:
Decision-making in the management of the COVID-19 pandemic has raised questions related to the disease progression in hypertensive patients according to their BP control and the presence of comorbidities or target organ involvement. It has been reported that HTN can worse the outcomes of patients infected by COVID-19. The aim of this study is to assess the clinical and sociodemographic parameters in this population of hypertensives treated in Primary Care, according to the severity of the disease progression (mild-asymptomatic or those who required hospital admission).

Design and Methods:
Multicentric, observational, cross-sectional, retrospective and analytical study. The patients were selected through a random sampling in 12 provinces in Spain, among patients older than 18y with treated hypertension and COVID-19 (PCR positive) under the primary care scope (119 investigators). Data collection time was 15 months (IQR= 5), from November 2020 to February 2022, outside the first wave.

Results:
1372 patients were recruited (51% women, mean age 67yo), smoking 12.5%, obesity 43.9%, diabetes 27.5%, controlled arterial hypertension 55.9% (BP<140/90). The severity of COVID-19 progression was: mild-asymptomatic 971 (71%), hospital admission 401 (29%), admission to ICU 74 (5%), death 48 (4%). Comparing the progression of the covid-19 disease of patients who requires hospital admission
vs
mild-asymptomatic, statistically significant differences were found between some comorbidities: COPD 21.7%
vs
11.9%, p<0.001; Diabetes 33.7%
vs
24.9%, p<0.05; Dyslipidemia 64.6%
vs
57.9%, p<0.05; CKD 21.5%
vs
11.1%, p<0.01; Stroke 9.5%
vs
5.5%, p<0.05; Atrial Fibrillation 17.7%
vs
7.2%, p<0.001; Heart Failure 17%
vs
5.8%, p<0.01; Ischemic Heart Disease 13.2%
vs
4.6%, p<0.001. As well as: GFR <60 ml/min 110 (27%)
vs
140 (14%), p<0.001; ACR (median, IQR) 72 mg/g (10-118)
vs
62 (7-115), p<0.05 .

Conclusions:
Among Spanish hypertensive patients in Primary Care, Covid-19 mortality achieves 4%. Some comorbidities such as diabetes, ischemic heart disease, atrial fibrillation, heart failure, stroke, chronic kidney disease or dyslipidemia, in which hypertension itself develop obvious vascular organ damage, results in worsening the outcomes of this population.
Abstract P301: The Proportion Of Physician Notes Addressing Elevated Blood Pressures Varies Dramatically Across Internal Medicine Specialties
Authors: Zetumer Samuel , Polgreen Philip , Suneja Manish , Polgreen Linnea
Published: September 2022

Introduction:
Approximately 20% of U.S. adults are unaware that they have a diagnosis of hypertension (HTN). Of those diagnosed, almost half are uncontrolled. This study provides a potential explanation of these care gaps: providers whose specialization does not include cardiovascular disease rarely document HTN, even when the patient has markedly elevated blood pressures (BPs) during their visit.

Methods:
We randomly sampled ten thousand patients with clinic visits after Jan 1, 2017.We then selected notes from only these visits with patient BPs above 140/90. The assessment and plans (A/Ps) of these notes were searched for words related to elevated BP or HTN. A/Ps with no mention of BP or HTN were considered not to have addressed hypertension. Results were grouped by the specialties listed in the figure.

Results:
We found 5674 clinic visits with associated BPs above 140/90. A/Ps from nephrology, cardiology, and general internal medicine visits mentioned elevated BP at least 50% of the time (in 55 of 77, 206 of 366, and 251 of 438 encounters, respectively). In contrast, A/Ps from encounters with allergy/immunology, endocrinology, and rheumatology specialists referenced the patient’s BP less than 10% of the time (in 3 of 52, 0 of 15, and 10 of 124 encounters, respectively. See figure).

Discussion:
Our results suggest specialties focused on the management of HTN are substantially more likely to address elevated BP in their documentation. However, there appears to be room for improvements in documentation across all specialties. Future studies will measure the impact of these missed opportunities on the diagnosis and management of HTN.
Abstract P309: Long Term Outcomes From A Resistant Hypertension Program
Authors: Szawaluk John , Bartone Cheryl , Clark Kelly , Huang Shaoming , Chung Eugene S
Published: September 2022

Background:
We report 10-year follow up data from a well-established Resistant Hypertension Program.

Methods and Results:
Between January 2012 and December 2021, there were 976 referrals, of which 357 were excluded, due to non-adherence/no-show. Therefore, demographic and clinical data from 619 patients are summarized in Table 1. Average duration of enrollment was 8.1 months with an average of 4.3 visits. The baseline and final data are shown in Table 2. Despite no weight loss, there were significant reductions in systolic BP (150.2 to 129.5 mmHg, p< 0.05) and diastolic BP (84.8 to 76.3 mmHg, p< 0.05). Average number of antihypertensive medications increased from 1.7 to 3.4, p< 0.05). There data are very similar to those from the first year of the program.

Conclusions:
Ten-year data from a well-established Resistant Hypertension Program maintained significant blood pressure reductions, similar to results from the first year of program.
Abstract P316: ANGIOTENSIN II-INDUCED LEFT VENTRICLE HYPERTROPHY AND DYSFUNCTION WERE EXAGGERATED BY
P2RX7
KNOCKOUT BUT UNAFFECTED BY P2RX7 PHARMACOLOGIC BLOCKADE
Authors: Berillo Olga , Shokoples Brandon , Comeau Kevin , Higaki Akinori , Caillon Antoine , Paradis Pierre , Schiffrin Ernesto L
Published: September 2022

Introduction:
We have demonstrated that the P2X7 receptor (P2RX7), which activates immune cells via binding of extracellular adenosine triphosphate, plays a role in hypertension and vascular injury. Angiotensin (Ang) II-induced hypertension, vascular injury and perivascular infiltration of activated CD8
+
T cells were attenuated by
P2rx7
knockout or P2RX7 pharmacologic blockade. However, whether P2RX7 is involved in Ang II-induced cardiac dysfunction and hypertrophy remains unknown.

Hypothesis:
We hypothesized that Ang II-induced left ventricular (LV) dysfunction and hypertrophy will be blunted equally by
P2rx7
knockout and P2RX7 antagonism.

Methods:
Ten-to-12-week-old male C57BL/6J wild-type (WT) and

P2rx7
-/-

mice were infused or not with Ang II (1000 ng/kg/min) for 14 days. A second group of WT mice infused with Ang II was infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle for 14 days. Cardiac LV function and remodeling were determined by ultrasound, and hypertrophic markers in cardiac ventricles by reverse transcription-quantitative PCR (RT-qPCR).

Results:
Ang II-induced increase in LV mass/body weight (6.3±0.2 vs 4.2±0.2 mg/g,
P
<0.001) and decrease in fractional shortening in WT mice (32.5±3.1% vs 43.8±2.4%,
P
<0.05) were exaggerated in

P2rx7
-/-

mice (7.3±0.5 mg/g and 20.2±3.1%,
P
<0.05), but not in mice receiving AZ10606120 (6.2±0.4 mg/g and 28.9±3.3%). Ang II-induced atrial natriuretic peptide (
Nppa
/ribosomal protein S16 [
Rps16
], 6.8±2.3 vs 1±0.1,
P
<0.001) and α-skeletal actin 1 expression (
Acta1
/
Rps16
, 6.3±1.3 vs 1±0.2,
P
<0.001) tended to be further increased in

P2rx7
-/-

mice (
Nppa
/
Rps16
: 13.5±2.4 and
Acta1
/
Rps16
: 11.9±2.4), but not in AZ10606120-treated mice (
Nppa
/
Rps16
: 5.5±0.7 and
Acta1
/
Rps16
: 5.6±0.8).

Conclusion:
Ang II-induced LV hypertrophy and dysfunction were exaggerated by
P2rx7
knockout but were not affected by P2RX7 pharmacologic blockade.
Abstract P317: ANGIOTENSIN II INFUSION CAUSED EXPANSION OF ACTIVATED ð NATURAL KILLER T CELLS IN MESENTERIC VESSEL PERIVASCULAR ADIPOSE TISSUE OF MICE
Authors: Berillo Olga , Comeau Kevin , Caillon Antoine , Leclerc Séverine , Shokoples Brandon , Mahmoud Ahmad , Andelfinger Gregor , Paradis Pierre , Schiffrin Ernesto L
Published: September 2022

Introduction:
The innate-like γδ T cells play a role in angiotensin II (AngII)-induced hypertension, vascular injury and T cell activation in perivascular adipose tissue (PVAT).

Hypothesis:
We hypothesized that single cell RNA sequencing (scRNA-seq) will reveal γδ T cell subpopulations in PVAT involved in hypertension, vascular injury and T cell activation.

Methods:
Male C57BL/6J mice were infused SC or not with 490 ng/kg/min AngII for 14 days (n=3). Hypertension was confirmed by tail cuff blood pressure measurement. Mesenteric vessels (MV) with PVAT were collected, lymph nodes removed, single cell suspension obtained and labeled with hashtag antibodies, T cells isolated by fluorescence-activated cell sorting, the 6 samples pooled in one tube, and scRNA libraries prepared with a Chromium Next GEM Single Cell 3’ Reagent Kit. Sequencing was done on an Illumina Novaseq 6000, and data analysed using Cell Ranger pipeline and Seurat tools. Cell subpopulations were validated by flow cytometry.

Results:
ScRNA-seq yielded 5,030 cells with 137,990 reads/cell and identified 11 T cell clusters. Subclustering of T cells expressing the T cell receptor (TCR) δ constant chain revealed 3 δ natural killer T (δNKT) (δNKT0, δNKT1 and activated δNKT cells) and 3 γδ T cell subpopulations (
Trgc1
low
effector memory, TCR δ variable 4
+
and apoptotic γδ T cells). AngII increased >2-fold the frequency of activated δNKT cells, and decreased by 74% δNKT0 cells. Gene expression profiling revealed that activated δNKT and δNKT0 cells could be identified using unique markers,
Cd28
and
Sell
, respectively. Flow cytometry showed that TCRδ
+
CD28
+
Sell
-
T cells were increased (393±57.2 vs 227±44.4 cells/MV-PVAT) and TCRδ
+
CD28
-
Sell
+
T cells decreased (21.6±4.1 vs 45.3±4.10 cells/MV-PVAT) in MV-PVAT of AngII vs sham-treated mice.

Conclusion:
This study identified an activated δNKT cell subpopulation in MV-PVAT that may play a role in AngII-induced hypertension, vascular injury and T cell activation.
Abstract P320: Transgenic Cre Drivers For Harvesting Podocytes And Endothelial Cells From Dahl Salt-sensitive Rats
Authors: Grzybowski Michael , Vanden Avond Mark , Usa Kristie , Klotz Jason , Palygin Oleg , Dwinell Melinda R , Cowley Allen W , Staruschenko Alexander , Liang Mingyu , Geurts Aron M
Published: September 2022

Complex phenotypes such as blood pressure regulation involve multiple organ systems, tissues, and specific cell types. Transgenic rodent models with the expression of fluorescent proteins under the control of tissue- and cell-type-specific promoters are powerful tools for identifying and isolating specific cells but have been primarily limited to mice. Our long-term goal is to establish a Cre-driver rat resource for conditional and physiologically predictive rat models of human diseases. We developed two Cre-driver transgenic strains of rats (SS/PodocinCreERT2 and SS/VECadCre) capable of activating a second Cre-sensitive tdTomato reporter transgene integrated into the rat Rosa26 locus in the Dahl salt-sensitive hypertension model background. Cells with reporter activation were identified under fluorescence microscopy or harvested using fluorescence-activated cell sorting (FACS). A tamoxifen-inducible Cre transgene under the control of the Nphs2 (podocin) gene promoter was used to harvest fluorescently labeled podocytes after tamoxifen injection. A constitutive Cre under the control of the Cdh5 (VE-Cadherin) gene promoter was used for the isolation of endothelial cells. Correspondingly, tens to hundreds of thousands of podocytes or endothelial cells were isolated from a single kidney or mesenteric artery. Isolated cells were enriched for specific marker genes and could be used in downstream assays including single-cell transcriptional profiling. These new Cre/reporter dual transgenic rat models provide a much-needed resource for the biomedical research community to study the role of these cell types in a broad range of health and disease modeling studies.
Abstract P324: Clinical Outcomes And 30-day Readmissions For Heart Failure With Preserved Ejection Fraction And Cardiorenal Syndrome: A Multicenter Database Analysis.
Authors: Shanah Layla , Mir Tanveer , Uddin Mohammed , Hussain Tanveer , Parajuli Tilachan , Bhat Zeenat Y
Published: September 2022

Background:
Literature regarding cardiorenal syndrome (CRS) outcomes among heart failure with preserved ejection fraction (HFpEF) is limited.

Objective:
This study sought to characterize CRS patients' clinical outcomes and 30-day readmission rates with HFpEF.

Methods:
Data was collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) Nationwide Readmissions Database (NRD) from January 1, 2018, to November 30, 2019. We used the International Classification of Diseases, 10
th
revision (ICD-10) diagnostic codes to identify encounters with CRS related to HFpEF.

Results:
Out of the 1,530,749 index HFpEF-CRS related hospitalizations (mean age 74.44±12.42years; 56.7%females), 1,295,302(82.1%) had CKD stage I-IV and 281,689(17.9%) had CKD stage V+. The CKD I-IV+ group had higher multi-organ complications including atrial fibrillation (AF) (33.7% vs 21.1%; p-value <0.001), acute kidney injury (AKI) (53.2% vs 20.1%; p-value <0.001), AKI requiring hemodialysis (53.2% vs 20.1%; p-value <0.001), respiratory failure (36.2% vs 34%, p-value <0.001), and ischemic stroke (2.21% vs 2%, p-value <0.001). However, the all-cause mortality for CRS with CKD V+ was higher as compared to CRS with CKD I-IV (4.83% vs 4.39%; p <0.001). HFpEF with CKD V+ had a significantly higher 30-day readmission rates compared to CKD I-IV subgroup (40.6% vs 15.8%; p-value <0.001). The predominant etiologies associated with 30-day readmissions among CKD I-IV in comparison to CKD V+ include cardiopulmonary (54.2%vs48.8%), and infectious (10.7%vs11.3%) diseases.

Conclusion:
Among HFpEF-CRS hospital encounters, progression of CKD stages is associated with higher 30-day readmission rates and all-cause mortality. These factors are accountable for a substantially increased healthcare burden. These findings suggest that regardless of CKD stages, patients with CRS should be monitored vigilantly during hospital admissions to avoid life-threatening complications.
Abstract P330: Nogo-B Regulates Vascular Sphingolipids To Impact Hepatic Gluconeogenesis And Blood Pressure
Authors: Rubinelli Luisa , Sasset Linda , Manzo Onorina , Del Gaudio Ilaria , Marino Alice , Sungho Jin , Ersoy Baran , Diano Sabrina , Di Lorenzo Annarita
Published: September 2022

Worldwide >1.6 billion of people are overweight or obese, a condition causally linked to type 2 diabetes (T2D), metabolic syndrome, cardiovascular diseases. In addition to precede the onset of diabetic CV complications, growing evidence implicate endothelial dysfunction to contribute to metabolic disorders. The sphingolipid ceramides, important membrane components and intracellular signaling molecules, have been implicated in insulin resistance and diabetes, and its vascular complications. However, mechanisms disrupting sphingolipid homeostasis and its impact on vascular and metabolic dysfunctions remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of the endoplasmic reticulum, inhibits sphingolipid
de novo
biosynthesis via serine palmitoyltransferase, first and rate liming enzyme, to impact vascular functions. Thus, the aim of this study was to investigate how Nogo-B regulation of sphingolipid signaling in the endothelium impacts metabolic and vascular homeostasis in obesity-T2D model.We discovered that in diabetic resistance arteries Nogo-B was overexpressed and correlated with a marked decrease of ceramides and sphingomyelins, vascular dysfunction, and hypertension. Interestingly, systemic, and endothelial genetic deletion of Nogo-B protected the mice from vascular dysfunctions and hypertension in diabetes, by preserving local sphingolipid metabolism and signaling. These findings, the first to investigate local mechanisms of sphingolipid metabolism derangement and its pathological implications, are a paradigm shift for the long-standing belief that vascular ceramide accrual underlies diabetic dysfunctions. Furthermore, our data also show that S1P secreted by the endothelium can downregulate hepatic gluconeogenesis, and that Nogo-B-mediated suppression of sphingolipid
de novo
biosynthesis can remove S1P brake on liver glucose production and exacerbates diabetes. Our findings suggest that suppression of endothelial sphingolipid signaling via Nogo-B underlies both vascular and metabolic dysfunctions in diabetes.
Abstract P334: Impairment Of Cognitive Ability In Middle-aged Renin Hypertensive Transgene Mice
Authors: Chen Shuzhen , Polaki Venkata , Sawant Harshal , Bihl Ji C , Wang Jinju
Published: September 2022

Background:
Vascular dementia (VD) is a severe cognitive impairment syndrome, characterized by a progressive memory and cognitive skill decline. Approximately 40 million people have dementia worldwide, and this number is expected to increase up to 115 million by 2050 due to the aging population. To date, no proven interventions are available to prevent VD. Chronic exposure to risk factors for vascular diseases, such as hypertension, diabetes, are implicated in the pathogenesis of VD, but the mechanisms remain to be fully understood.

Methods:
In this study, we utilized a renin hypertensive transgene mice (R+) mouse model to explore how the elevated blood pressure affects the pathogenesis of VD. We analyzed the cognitive ability, cerebral microvascular density, and neurons in young R+ mice, middle-aged R+ mice, and the wild type (WT) mice.

Results:
We found that middle-aged R+ mice had increased blood pressure associated with cognitive impairment as revealed by prolonged latency to target in morris water maze as compared to the young R+ mice and age-matched WT mice did. Meanwhile, our data showed that the R+ mice had brain microvessel rarefaction in the cortex and hippocampus, associating with a significantly low number of neurons in the hippocampus region (subiculum) as compared to that in WT mice.

Conclusion:
Our data have demonstrated that middle-aged renin transgene mice have impaired cognitive ability, accompanying with a low density of microvessel and fewer neurons, suggesting that chronic cerebral hypoperfusion might further damage neuron which could contribute to the progress of VD.
Abstract P345: Inhibition Of Nuclear Receptor Retinoid-related Orphan Receptor γt Attenuates Interleukin-17A Production And Ameliorates Angiotensin II-induced Neuroinflammation And Hypertension In Rats
Authors: Yu Yang , Xue Baojian , Chen Qing , Irfan Nafis Md , Johnson Alan K , Wei Shunguang
Published: September 2022

Interleukin (IL)-17A, a key inflammatory mediator produced primarily by T helper (Th) 17 cells, has been implicated in the pathogenesis of cardiovascular diseases including hypertension and heart failure. IL-17A can access the brain by disrupting blood-brain barrier (BBB) integrity to induce neuroinflammation. We previously reported that IL-17A contributes to angiotensin (ANG) II-induced hypertension via promoting neuroinflammation and sympathetic excitation. The nuclear receptor retinoid-related orphan receptor γt (RORγt) is a master transcription factor regulating Th17 cell differentiation. Here, we sought to determine whether systemic inhibition of RORγt attenuates IL-17A production and diminishes ANG II-induced neuroinflammation and hypertension. Sprague-Dawley rats received a 2-week subcutaneous (sc) infusion of ANG II (150 ng/kg/min) combined with daily sc injection of a RORγt inhibitor digoxin or vehicle (VEH). Compared with the control animals, blood pressure (162±5* vs 118±3 mmHg, *P<0.05) and sympathetic tone as indicated by blood pressure change in response to ganglionic blockade (55±5* vs 23±3 mmHg) were increased in ANG II+VEH rats, which were reduced (38-41%*) in ANG II+digoxin rats. ANG II+VEH rats also had elevated RORγt mRNA in peripheral blood mononuclear cells (PBMCs: 3.38±0.70* vs 1.12±0.22) and higher IL-17A levels in plasma (23.22±5.85 * vs 4.30±0.66 pg/mL), along with increased IL-17A levels in cerebrospinal fluid (CSF: 11.89±1.91* vs 2.01±0.55 pg/mL), mRNA of IL-17A (3.02±0.48* vs 1.07±0.17), cytokines tumor necrosis factor (TNF)-α (2.78±0.45* vs 1.04±0.12) and IL-1β (2.57±0.53* vs 1.03±0.14) in the hypothalamic paraventricular nucleus (PVN), a key cardiovascular-related center in the brain. Although RORγt mRNA was unchanged in PBMCs, levels of IL-17A in plasma and CSF, mRNA of IL-17A, TNF-α and IL-1β in the PVN was reduced (41-62 %*) in ANG II+digoxin rats. Additionally, mRNA of caveolin-1 (2.26±0.39* vs 1.06±0.17), a marker of the BBB permeability, was increased in the PVN in ANG II+VEH rats and decreased (43%*) in ANG II+digoxin rats. These data suggest that RORγt inhibition improves ANG II-induced hypertension and sympathetic activation probably by reducing IL-17A production and neuroinflammation.
Abstract P346: Cardiac Arrest During Delivery Hospitalization And Severe Hypertensive Disorders Of Pregnancy, United States, 2017-2019
Authors: Ford Nicole D , DeSisto Carla L , Galang Romeo R , Kuklina Elena V , Sperling Laurence , Ko Jean Y
Published: September 2022

Background:
Cardiac arrest is a rare and sometimes fatal maternal complication. Severe hypertensive disorders of pregnancy (HDP) including preeclampsia with severe features, eclampsia, and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome are risk factors for maternal cardiac events. Surveillance on cardiac arrest and severe HDP during delivery is critical to informing evidence-based strategies to reduce pregnancy-related death.

Methods:
Using pooled data from the National Inpatient Sample from 2017-2019, we identified delivery hospitalizations among women aged 12-55 years. Delivery hospitalizations, cardiac arrest, and maternal medical conditions were identified using ICD-10-CM codes. Survival to hospital discharge was based on patient discharge disposition. Prevalence of cardiac arrest, severe HDP, and survival following cardiac arrest were calculated. We estimated the prevalence of severe HDP among delivery hospitalizations with cardiac arrest, cardiac arrest frequency among delivery hospitalizations with severe HDP, and survival to hospital discharge with co-occurring cardiac arrest and severe HDP. All estimates were weighted to account for complex sampling.

Results:
During 2017-2019, an estimated 10,921,784 delivery hospitalizations among which 1,465 cardiac arrests were identified. Overall cardiac arrest prevalence was 13.4 per 100,000 delivery hospitalizations (95% CI, 11.9-14.9). Of these, 1,005 (68.6% [95% CI, 63.2-74.0]) survived to hospital discharge. Overall prevalence of severe HDP was 2.7% (95% CI, 2.6-2.7) compared with 15.4% (95% CI 11.2-19.5) of delivery hospitalizations with cardiac arrest. Frequency of cardiac arrest per 100,000 delivery hospitalizations with severe HDP was 76.9 (95% CI, 54.6-99.2). Survival to hospital discharge with co-occurring cardiac arrest and severe HDP was 77.8% (95% CI, 65.6-89.9).

Conclusion:
Delivery hospitalizations affected by cardiac arrest are rare, and over two thirds survived to hospital discharge. Cardiac arrest disproportionately affected delivery hospitalizations among patients who had severe HDP.
Abstract P349: Decreased Complement Component C3 In Islets Is Associated With A Reduction In Pancreatic Beta Cell Area In Rat Offspring Following Chronic Placental Ischemia-induced Hypertension
Authors: Regal Jean F , Cedars Melissa A , Root Kate M , Huchthausen Margaretta E , Akhaphong Brian , Alejandro Emilyn U
Published: September 2022

Gestational hypertension with or without low birth weight is associated with increased risk for Type 2 diabetes in offspring. Pancreatic beta cell mass is set very early in life and can influence whether an individual develops Type 2 diabetes. We previously demonstrated that postnatal day (PD)13 female offspring of rats subjected to chronic placental ischemia-induced hypertension had significantly reduced beta cell area. Previous studies in humans have noted increased circulating C3 in Type 2 diabetics, as well as an important role for intracellular complement C3 in maintaining integrity of the beta cell in the islet. Thus, we hypothesized that decreased C3 in islets is associated with reductions in beta cell area in rat offspring following placental insufficiency. The rat Reduced Uterine Perfusion Pressure (RUPP) model was used to mechanically induce placental insufficiency in the dam by placing silver clips on abdominal aorta and uterine arteries on gestation day 14 of a 21-day gestation, resulting in hypertension in the dam. Pancreatic islets and acinar were isolated by collagenase perfusion and hand picking from PD13 female offspring of RUPP and Sham dams. The concentration of C3 in serum, isolated islets and acinar was determined by ELISA. C3 was significantly increased in serum of female RUPP compared to female Sham offspring. In contrast, C3 in islets was significantly decreased in RUPP female offspring compared to Sham with no significant differences detected in acinar C3 concentrations. Thus, these data suggest that decreased C3 in islets of PD13 offspring may contribute to reduction of beta cell area and long-term susceptibility for Type 2 diabetes.
Abstract P354: Pi3kg Signalling Is Crucial For Regulating The Cross Talk Between Cd8 T Lymphocytes And Vasculature In Hypertension
Authors: Perrotta Marialuisa , Perrotta Sara , Pallante Fabio , Carnevale Lorenzo , Migliaccio Agnese , Fardella Stefania , LEMBO GIUSEPPE , Carnevale Daniela
Published: September 2022

CD8 effector T cells infiltrate target organs of hypertension (HTN). Phosphatidylinositol 3 kinase gamma (PI3Kγ) is a lipid kinase mainly distributed in immune and cardiovascular systems. In our previous work, we demonstrated a crucial role of PI3Kγ in blood pressure (BP) regulation. Here, we aim to identify signaling pathways involved in the acquisition of CD8 effectors functions in HTN. By taking advantage of a knock-in mouse model expressing a constitutively active PI3Kγ isoform (PI3Kγ
CX/CX
), we tested the hypothesis that PI3Kγ regulates CD8 T cell trafficking in HTN. First, we found that PI3Kγ
CX/CX
mice were spontaneously hypertensive (SBP
mmHg
: PI3Kγ
CX/CX
: 131±1 vs WT: 108±0.5, p<0.001), displaying a significant activated CD8 T cells infiltration in perivascular spaces of kidneys (CD8+CD44+CD69 effector cells: PI3Kγ
CX/CX
: 7.6±2 vs WT: 1.95±0.2, p<0.001). To test a direct role of PI3Kγ in CD8 T cells, we purified these cells from PI3Kγ
CX/CX
spleens and performed an adoptive transfer of these cells in WT mice. Recipient mice increased BP and accumulated activated CD8 T cells in kidneys (SBP
mmHg
:CD8
CX/CX
: 128±2 vs CD8
WT
: 103±2, p<0.001). To test the interaction of CD8 T cells with vasculature, we co- cultured CD8 from PI3Kγ
CX/CX
mice with pressurized resistance arteries from WT mice for 3 days, finding that activated CD8 T cells significantly increased myogenic tone (an important regulator of BP) (%MT: CD8
CX/CX
: 31±1; CD8
WT
: 19±1, p<0.001). To deepen our hypothesis, we generated a conditional KO for PI3Kγ in CD8 T cells by crossing PI3Kγ
flox
mice with CD8a1cre-mice. We measured BP of PI3Kγ
flox
-CD8a1cre- mice observing that they were protected from BP increase upon Angiotensin II infusion by osmotic minipumps (SBP
mmHg
: PI3Kγ
flox
-CD8a1cre: 126±2 vs WT: 138±3, p<0.001).Then, we co- cultured CD8 T cells from PI3Kγ
flox
-CD8a1cre-mice with pressurized resistance arteries from WT mice, finding that CD8 T cells lacking PI3Kγ are unable to increased MT (%MT: PI3Kγ
flox
-CD8a1cre: 13±1 vs WT: 22±3, p<0.001). Taken together these data show that PI3Kγ signaling in CD8 T cells is crucial for priming of immune response in HTN.
Estimated Benefits and Risks of Using a Reduced-Sodium, Potassium-Enriched Salt Substitute in India: A Modeling Study
Authors: Marklund Matti , Tullu Fikru , Raj Thout Sudhir , Yu Jie , Brady Tammy M. , Appel Lawrence J. , Neal Bruce , Wu Jason H.Y. , Gupta Rachita
Published: September 2022

Background:

Salt substitution (ie, replacement of table and cooking salt with potassium-enriched salt substitutes) is a promising strategy to reduce blood pressure and prevent cardiovascular disease, particularly in countries like India where there is high sodium intake, mainly from discretionary salt, and low potassium intake. Life-threatening hyperkalemia from increased potassium intake is a postulated concern for individuals with chronic kidney disease.

methods:

We used comparative risk assessment models to estimate the number of (1) cardiovascular deaths averted due to blood pressure reductions; (2) potential hyperkalemia-related deaths from increased potassium intake in individuals with advanced chronic kidney disease; and (3) net averted deaths from nationwide salt substitution in India. We evaluated a conservative scenario, based on a large, long-term pragmatic trial in rural China; and an optimistic scenario informed by our recent trial in India. Sensitivity analyses were conducted to assess the robustness of the findings.

Results:

In the conservative scenario, a nationwide salt substitution intervention was estimated to result in ≈214 000 (95% uncertainty interval, 92 764–353 054) averted deaths from blood pressure reduction in the total population and ≈52 000 (22 961–80 211) in 28 million individuals with advanced chronic kidney disease, while ≈22 000 (15 221–31 840) hyperkalemia-deaths might be caused by the intervention. The corresponding estimates for the optimistic scenario were ≈351 000 (130 470–546 255), ≈66 000 (24 925–105 851), and ≈9000 (4251–14 599). Net benefits were consistent across sensitivity analyses.

Conclusions:

Modeling nationwide salt substitution in India consistently estimated substantial net benefits, preventing around 8% to 14% of annual cardiovascular deaths. Even allowing for potential hyperkalemia risks there were net benefits estimated for individuals with chronic kidney disease.
Resistance to Antihypertensive Drugs: Is Gut Microbiota the Missing Link?
Authors: Kyoung Jun , Atluri Rohit R. , Yang Tao
Published: September 2022

Microbiota colonization begins at birth and continuously reshapes throughout the course of our lives, resulting in tremendous interindividual heterogeneity. Given that the gut microbiome, similar to the liver, houses many categories of catalytic enzymes, there is significant value in understanding drug-bacteria interactions. The discovery of this link could enhance the therapeutic value of drugs that would otherwise have a limited or perhaps detrimental effect on patients. Resistant hypertension is one such subset of the hypertensive population that poorly responds to antihypertensive medications, resulting in an increased risk for chronic cardiovascular illnesses and its debilitating effects that ultimately have a detrimental impact on patient quality of life. We recently demonstrated that the gut microbiota is involved in the metabolism of antihypertensive drugs and thus contributes to the pathophysiology of resistant hypertension. Due to a lack of knowledge of the mechanisms, novel therapeutic approaches that account for the gut microbiota may allow for better therapeutic outcomes in resistant hypertension. Therefore, the purpose of this review is to summarize our current, albeit limited, understanding of how the gut microbiota may possess particular enzymatic activities that influence the efficacy of antihypertensive drugs.
An Interpretative View of the Origin of the Early Chinese Revolution from the Perspective of Secret Societies: Retrospect and Reflections from the History of Social Thought, Part II
Authors: Wang (王旭) Xu
Published: September 2022

The development of the Chinese revolutionary movement in the early twentieth century absorbed cultural resources from traditional secret societies and associations. The White Lotus, the Tiandihui, the Gelaohui, the Triad, and the various secret societies that had emerged in the Taiping and the Boxer rebellions were all incorporated into the discourse system of revolutionary history. The secret societies’ slogans of “overthrow the Qing and restore the Ming” and “rob the rich to help the poor” merged with the revolutionaries’ platform of “drive out the Manchus” and “relief for people’s livelihood,” and finally advanced the success of the Xinhai Revolution and was turned into a coherent historical narrative. After the founding of the Republic of China, Sun Yat-sen and Song Jiaoren carefully assessed the function of secret societies and distinguished them from modern political parties. On the other hand, leaders of the Communist Party, such as Mao Zedong, Qu Qiubai, Yun Daiying, and Chen Duxiu, emphasized the ideological transformation of secret societies and the suitable role they could play in the revolution, thus showing a dynamic strategy of allying with these organizations. The history of the relationship between the Chinese revolution and secret societies reflects the changing characteristics and logic of the underclass of Chinese society.
Immigration in an Era of Mass Reentry: Does Immigrant Concentration Guard Against Serious Recidivism?
Authors: Ramos Javier
Published: September 2022

Objectives

Determine whether the protective role of immigrant concentration extends to individuals with prior criminal histories such as ex-prisoners.

Methods

The present study used hierarchical logistic regression to examine the association between concentrated immigration and serious recidivism among a cohort of 182,509 ex-inmates nested within 957 zip codes in Florida. The study also considered whether this relationship is applicable to inmates from all racial and ethnic backgrounds.

Results

Results indicate that ex-prisoners have a 21 percent lower likelihood of recidivism when they return to communities with substantial numbers of foreign-born residents. This effect, however, is stronger for some populations than others.

Conclusions

Immigration serves as a protective feature for even high-risk populations. While this relationship does differ across race and ethnicity, no group experienced a crime-enhancing effect when returning to a community categorized by high immigration. The findings contribute to the burgeoning literature on immigration and crime by demonstrating that immigrant communities provide ex-prisoners with a pro-social context that diminishes their risk for serious recidivism.
Optimization path of green credit to energy consumption structure: A symbiotic development perspective of resource-based and non-resource-based industries
Authors: Qiu Wei , Bian Yaojun , Irfan Muhammad , Li Yanan
Published: September 2022

In the context of ecological environment construction, how to create a new development pattern in which environment and economy are coordinated has become an important goal of the Chinese government. From the perspective of the symbiotic development of resource-based industries and non-resource industries, this study discusses the path of green credit optimization of energy consumption structure by using the space Durbin model, based on the panel data from 30 Chinese provinces from 2006 to 2019. The study results are as follows: Both green credit and energy consumption structure have a significant positive spatial correlation. Furthermore, the energy consumption structure of local and adjacent areas is significantly optimized by green credit. Additionally, for non-resource-based regions, although green credit has no spatial spillover, it can significantly improve the local energy consumption structure, while green credit in resource-based regions significantly inhibits the optimization of the energy consumption structure in local and adjacent regions. Finally, from the perspective of the symbiotic development of resource-based industries and non-resource industries, although green credit can significantly improve the local energy consumption structure, it will inhibit the optimization of the energy consumption structure in adjacent areas. Therefore, government departments not only need to implement green credit policies according to local conditions but also actively guide exchanges and cooperation between resource-based industries and non-resource industries. This move promotes the symbiotic development of resource-based industries and non-resource industries and simultaneously improves the utilization efficiency of green credit, and optimizes the energy consumption structure.
DSM-5-TR: Salient Changes
Authors: Bradley Loretta , Noble Nicole , Hendricks Bret
Published: September 2022

The Diagnostic and Statistical Manual of Mental Disorders (DSM) is considered the authority for mental health diagnosis. Further, it is highly respected by counselors and especially by couple and family counselors as well as insurance companies. The DSM was initially published in 1952. Since its original publication 70 years ago, the DSM has experienced seven revisions with the most recent revision, the DSM-5-TR, occurring in March 2022. The focus of this article is to help couple and family counselors not only be aware of the changes but more importantly, the focus is directed toward helping them understand the changes.
A fast and efficient path elimination algorithm for large-scale multiple common longest sequence problems
Authors: Yu Changyong , Lin Pengxi , Zhao Yuhai , Ren Tianmei , Wang Guoren
Published: September 2022

Background

In various fields, searching for the Longest Common Subsequences (LCS) of Multiple (i.e., three or more) sequences (MLCS) is a classic but difficult problem to solve. The primary bottleneck in this problem is that present state-of-the-art algorithms require the construction of a huge graph (called a direct acyclic graph, or DAG), which the computer usually has not enough space to handle. Because of their massive time and space consumption, present algorithms are inapplicable to issues with lengthy and large-scale sequences.

Results

A mini Directed Acyclic Graph (mini-DAG) model and a novel Path Elimination Algorithm are proposed to address large-scale MLCS issues efficiently. In mini-DAG, we employ the branch and bound approach to reduce paths during DAG construction, resulting in a very mini DAG (mini-DAG), which saves memory space and search time.

Conclusion

Empirical experiments have been performed on a standard benchmark set of DNA sequences. The experimental results show that our model outperforms the leading algorithms, especially for large-scale MLCS problems.
Early recurrence after cryoballoon versus radiofrequency ablation for paroxysmal atrial fibrillation: mechanism and implication in long-term outcome
Authors: Wei Yue , Bao Yangyang , Lin Changjian , Xie Yun , Luo Qingzhi , Zhang Ning , Wu Liqun
Published: September 2022

Background

Early recurrence (ER) after catheter ablation for atrial fibrillation (AF) has been considered as a common phenomenon but its mechanism and implication in long-term outcome has not been fully elucidated. We aimed to clarify the relation between post-ablation inflammation and ER after cryoballoon ablation (CBA) or radio-frequency ablation (RFA) and evaluate the clinical significance of ER.

Methods

A total of 154 patients with paroxysmal AF undergoing ablation were consecutively recruited, including 90 patients undergoing RFA (RF group) and 64 patients undergoing CBA (CB group). Myocardial injury and inflammation biomarkers were analyzed before and 6 h, 24 h and 48 h after ablation. Acute early recurrence (AER), non-acute early recurrence (NAER) and late recurrence (LR) was defined as recurrence of atrial tachyarrhythmia during 0–3, 4–90 days and beyond a 90-day blanking period after ablation.

Results

Cardiac troponin I was significantly higher in CB group while C reactive protein (CRP) and Ratio Neutrophil/Lymphocyte were more elevated in RF group. Higher CRP level after RFA was significantly associated with AER in RF group and lower CRP level after CBA was predictive of AER in CB group. In addition, average cryoablation duration was positively correlated with CRP level after CB group. Cox regression revealed that NAER and left atrial diameter were associated with LR in RF group, while AER and NAER were predictive of LR after CBA.

Conclusions

Post-ablation inflammation was greater in RFA than in CBA. Excessive inflammatory response may be an important factor of AER after RFA. AER after CBA was related with lower inflammation and predictive of LR. Further investigations are still warranted to address on these findings.
Adherence to and usefulness of the national treatment guideline for urinary tract infections (UTI) in a risk area
Authors: van Driel A. A. , Mulder M. , Stobberingh E. E. , Verbon A.
Published: September 2022

Background

To optimize antibiotic treatment and decrease antibiotic resistance, national treatment guidelines are available for urinary tract infections (UTIs) in general practice. The usefulness of these guidelines in risk areas for antimicrobial resistance such as cross border regions or areas with dense agriculture, is unknown.

Methods

Midstream urine samples from women with symptoms of acute UTI visiting general practitioners (GPs) in the Westland area, a dense agriculture area, were microbiologically analysed, and patient characteristics, symptoms, previous and present antibiotic treatment were collected. The National Nivel data were used as reference for antibiotic resistance.

Results

Of 310 women with symptoms of uncomplicated UTI, 247 (80%) had a culture proven E. coli UTI. Empirical antibiotic therapy was prescribed to 148 patients (48%) in total; in 7% of women with a negative and 52% with a positive urine culture. Having more than one symptom was associated with the prescription of antibiotics; travel history or previous antibiotic use for UTI were not. The isolated uropathogens were susceptible to the empiric antibiotic therapy in 98% of patients. Resistance to co-amoxiclav was higher (22%) than reported in the national data of 2004 (12%), 2009 (13%) and 2014 (9%), as was the prevalence of extended spectrum β-lactamase (ESBL): 3.4% in our study versus 0.1%, 1% and 2.2% in the national data respectively.

Conclusion

The presence of environmental and socio-demographic risk factors for antibiotic resistance did not influence the empiric choice nor susceptibility for antibiotics advised by the national guidelines in women with uncomplicated UTI.
Diffuse lamellar keratitis as a rare complication of diamond burr superficial keratectomy for recurrent corneal erosion: a case report
Authors: Lin Hung-Yu , Ho Wei-Ting
Published: September 2022

Background

To present a case with a history of laser in situ keratomileusis (LASIK) developing diffuse lamellar keratitis (DLK) after diamond burr superficial keratectomy (DBSK) for recurrent corneal erosion (RCE).

Case presentation

A 25-year-old man presented with multiple episodes of RCE one year after femtosecond-assisted LASIK for myopia correction. Because conservative treatments failed to halt the repetitive attack of RCE, he underwent epithelial debridement and DBSK. However, severe foreign body sensation and blurred vision developed on postoperative day one. The next day, slit lamp biomicroscopy revealed DLK manifested as diffuse granular infiltrates at the flap interface. After topical corticosteroid treatment, the inflammation resolved gradually, and his vision recovered to 20/20.

Conclusions

Diffuse lamellar keratitis is a rare post-LASIK complication that can be triggered by DBSK, which causes impairment of the corneal epithelial integrity and subsequent inflammation at the flap interface. For post-LASIK patients with RCE, alternative treatments, such as anterior stromal puncture, may be considered to avoid extensive disruption of corneal epithelium and DLK development depending on the size and the location of the lesions.
Knowledge of fermentation and health benefits among general population in North-eastern Slovenia
Authors: Šikić-Pogačar Maja , Turk Dušanka Mičetić , Fijan Sabina
Published: September 2022

Background

Fermented foods are staples of the human diet and fermentation process has been used by humans for thousands of years. The preparation of fermented foods was performed in the past without knowledge of the role of microorganisms involved. Nowadays, fermented foods, due to their proclaimed health benefits for consumers, are becoming increasingly popular. Our study was constructed to provide data on awareness and use of fermented foods among people in North-eastern Slovenia.

Methods

The cross-sectional study included 349 individuals (16–89 years of age). An online survey was designed to assess the participants' knowledge of fermentation, fermented foods, the consumption of fermented foods and awareness of the health benefits. Data were collected from March to June 2021 and analyzed using IBM SPSS 27.0.

Results

Compared with the youngest participants (< 21 years) knowledge of fermentation was higher in older individuals (p < 0.001). More than a half of the participants recognized the role of lactic acid bacteria and yeasts in fermentation process, however, only 18.3% of participants were aware of the role of the molds. Only 25.9% of the participants have become acquainted with fermented foods at home and 62.2% of them were aware of health benefits of fermented foods, but mostly on gastrointestinal health and the immune system.

Conclusions

As people today live predominantly in urban areas and incline towards westernized foods, they often lack the knowledge of fermentation and awareness regarding the nutritional value of fermented foods and their preparation. Steps should be taken to educate younger generations regarding the health benefits of fermented foods especially considering that most of them expressed their interest in learning more about the process.