bluuebunny/crossref_metadata_2025 huggingface dataset:
Body Language: Making Love in Lyric in Romeo and Juliet
Authors: Lees-Jeffries Hester
Published: January 2023

With a particular focus on an intensive close reading of the scenes between the lovers and their portrayal of desire and intimacy, this essay discusses how Shakespeare transforms lyric poetry, especially its formal features, not simply into dramatic poetry but into theatre, demonstrating how Shakespeare creates the lovers’ world and the passionate intimacy of their relationship through the embodiment of lyric forms, especially the sonnet, the epithalamium, and the aubade. Explicitly thinking about bodies (and bodies on stage) rather than ‘the body’, it draws on a number of Shakespeare’s sources, especially Sidney’s Astrophil and Stella and Marlowe’s Hero and Leander, as well as Arthur Brooke’s Romeus and Juliet, exploring in precise detail how Shakespeare works with them, the particularity of his transformations, and their effects.1
Dollar and Exports
Authors: Bruno Valentina , Shin Hyun Song
Published: January 2023

The strength of the U.S. dollar has attributes of a barometer of dollar credit conditions, with a stronger dollar associated with tighter dollar credit conditions. We find that following dollar appreciation, exporters that are more reliant on dollar-funded bank credit suffer a greater decline in credit and slowdown in exports, including those exporting to the United States. Our findings shed light on the role of the U.S. dollar in the interaction between financial globalization and international trade and show a novel channel of exchange rate transmission that goes in the opposite direction to the competitiveness channel.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Bradykinin B1 receptor antagonist protects against cold stress–induced erectile dysfunction in rats
Authors: Ruze Abudureyimujiang , Wang Binghua , Jin Jin , Hou Pengcheng , Tuerxun Diliyaer , Amuti Siyiti
Published: January 2023

Background

Erectile dysfunction (ED) demonstrates seasonal variation with higher rates in winter, and we hypothesize that endothelial damage in erectile tissue caused by bradykinin receptor B1 (B1R) might be detrimental to this change.

Aim

To find out direct correlations between cold stress and ED, through which to further investigate the functional roles of B1R in erectile tissue and to elucidate the therapeutic roles of the B1R antagonist in a cold stress–induced ED rat model.

Methods

Cold stress rat models are established through long-term intermittent exposure to low temperature. After their erectile function was assessed, ED rats were treated with the B1R antagonist through intraperitoneal injection. Penile tissues were obtained at the end of the experiment after measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP); the location and distribution of cytokine expression were determined by immunohistochemistry; cytokine levels and NOS and CD31 expression were detected by Western blotting; and collagen fibers and smooth muscles were observed through Masson staining.

Outcomes

Cold stress impairs erectile function, and the B1R antagonist protects against it.

Results

We observed decreased erection frequency, prolonged erection latency time, decreased ICP/MAP, overexpression of B1R, increased expression of cytokines on cavernous sinus endothelium, and increased levels of collagen fibers/smooth muscles on erectile tissue in response to cold stress. Also, NOS and CD31 expression was downregulated. B1R antagonist treatment shows enhanced erectile function through increased erection frequency, shortened erection latency time, and increased ICP/MAP. Also, it reduces collagen fibers/smooth muscles, TNF-α, TGF-β1, and IL-6 and upregulates the expression of nNOS and CD31.

Clinical Translation

Our findings cast new light on the correlations between cold stress and erectile function and potential new applications of existing B1R antagonist drugs in the field of ED.

Strengths and Limitations

Our data support that cold stress impairs erectile function. B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it, and B1R inhibition protects against fibrosis and endothelial damage. Other ways of B1R antagonist blocking methods in different types of ED still need to be investigated.

Conclusion

Long-term intermittent cold stress impairs erectile function, and B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it. B1R inhibition also protects against fibrosis and endothelial damage. Our data support the hypothesis that cold stress impairs erectile function and that B1R blockade ameliorates the symptoms of ED, possibly by reversing fibrosis and endothelial damage in erectile tissue.
A systematic review to assess the burden of ischemic priapism in patients with sickle cell disease
Authors: Nellesen Dave , Lucas Sedge , Liu Che-Rung , Bhor Menaka , Paulose Jincy , Burnett Arthur L
Published: January 2023

Introduction

Ischemic priapism is a serious condition characterized by a persistent and painful involuntary erection. Patients with sickle cell disease (SCD) are at an elevated risk of experiencing priapism, with approximately 40% experiencing priapism during their lifetime.

Objectives

This systematic literature review (SLR) sought to identify studies reporting the clinical, humanistic, and economic burden of SCD-related priapism.

Methods

MEDLINE, Embase, Cochrane CENTRAL/CDSR, and 14 congresses were searched. Results were screened against predefined criteria and studies assessing relevant aspects of burden for human patients with SCD-related priapism were included. Outcomes of interest included rates of erectile dysfunction (ED), other disease-related complications, health-related quality of life (HRQoL), and economic burden.

Results

Of 1,236 publications identified, 34 were included. Most studies were retrospective observational (21). Sample size varied widely (range, 15–10,788). Study publication dates ranged from November 1980 through April 2018. Twenty-one studies reported clinical burden, with findings falling into 4 categories-priapism duration, recurrence frequency, incidence/severity of ED, and other complications. Nineteen studies reported humanistic burden, finding limited use of validated HRQoL measures such as the International Index of Erectile Function and the Priapism Impact Profile. Other patient-reported humanistic outcomes included worse scores on sleep-related indices and low rates of satisfactory intercourse. Eight studies reported economic burden. Direct treatment costs ranged from $4,996 for patients without penile operations to $22,906 (2019 USD) for patients receiving transfusions and urologic procedures.

Conclusions

This SLR identified 34 studies providing evidence of the burden of priapism for patients with SCD, including painful complications and diminished physical, mental and sexual function.
A systematic review of sexual health consequences among women with lichen sclerosus
Authors: Smith Alyssa B , Muhammad Náimah I , Cigna Sarah T , Krapf Jill M
Published: January 2023

Introduction

Lichen sclerosus (LS) is a chronic inflammatory skin condition predominantly affecting the vulva. Studies have shown high rates of sexual dysfunction in patients with LS; however, the sexual effects of the condition are poorly acknowledged.

Objectives

We sought to identify sexual health consequences among women with vulvar LS through systematic review of available literature.

Methods

A systematic review of the literature was conducted to find reports on sexual health consequences among women with LS. PubMed, MEDLINE, and Scopus were queried. Included articles were observational studies evaluating women with LS and their sexual health and randomized controlled trials or comparative studies utilizing a validated sexual health measure before intervention among the same population. Articles must have been written in English and published from January 1991 to April 2022.

Results

The search produced 683 references, including 32 articles that met criteria for full-text review and 20 reported studies that met inclusion criteria. Two studies investigated the impact of LS on interpersonal relationships, 6 studies evaluated sexual symptoms, 16%-60% reported sexual dysfunction, and 22%-56.7% reported dyspareunia. Also described were decreased sexual frequency and satisfaction, negative impact on sexual relationships, and feelings of inadequacy. Eight publications evaluated the Female Sexual Function Index (FSFI); all described studies that demonstrated a central tendency less than 26.55. Four publications evaluated the Female Sexual Distress Scale (FSDS); all demonstrated average scores greater than 12. Two publications evaluated the Female Genital Self-Image Scale (FGSIS), both found decreased scores compared to controls. Four publications evaluated the Dermatology Life Quality Index (DLQI); impact on quality of life was small to very large, with sexual difficulties affecting most study patients. One publication evaluated the Vulvar Quality of Life Index (VQLI); sexuality was the second highest-scoring subgroup.

Conclusions

Sexual health consequences of LS include sexual pain, dysfunction, and distress; negative genital self-image; and negative impact on sexual relationships. Women with LS experience a negative impact on quality of life, particularly related to sexual functioning.
PL-4: INSIGHTS INTO MOLECULAR MECHANISMS OF HYPERTENSION FROM HUMAN GENETICS
Authors: Lifton Richard P.
Published: January 2023

Identification and investigation of rare patients with extreme forms of high and low blood pressure has led to the identification of specific genes whose mutation results in these outlier phenotypes. These rare mutations converge on genes that mediate or regulate the renal reabsorption of Na-Cl. Mutations that increase or decrease renal salt reabsorption respectively increase or decrease blood pressure. Mutations that cause hypertension include gain of function mutations in subunits of the epithelial Na+ channel (ENaC) and in any of eight genes that cause constitutive activity of ENaC by its stimulation via its major regulator, the mineralocorticoid receptor, the target of aldosterone signaling; these increase salt reabsorption in the distal nephron. Conversely, mutations that cause hypotension include loss of function mutations in ENaC subunits, but also mutations the thiazide-sensitive Na-Cl cotransporter (NCC) or a K+ channel required for cotransporter function that act in the distal convoluted tubule (DCT), or mutations in the Na-K-2Cl cotransporter as well as K+ and Cl- channels expressed in the thick ascending limb of Henle that are required for normal Na-Cl reabsorption in this nephron segment. ENaC, the Na-Cl cotransporter and the Na-K-2Cl cotransporter, as well as the mineralocorticoid receptor are all commonly used targets for treatment of hypertension and/or diuresis.

In addition to these genes, genetic studies also identified a previously unrecognized pathway that regulates the balance between renal salt reabsorption and K+ secretion. Mutations in the kinases WNK1 or WNK4, or genes that mediate their degradation via ubiquitylation, CUL3 and KLHL3 cause hypertension with hyperkalemia. Activity of WNK1 and WNK4 stimulates activation of NCC promoting Na-Cl reabsorption in the DCT, reducing Na-Cl- delivery distally, thereby limiting ENaC activity and limiting K+ secretion in the distal nephron. Conversely, hyperkalemia inhibits WNK activity, promoting distal Na-Cl delivery and maximizing K+ secretion. Angiotensin II signaling promotes WNK activity, increasing Na-Cl reabsorption in the DCT and inhibiting K+ secretion, while hyperkalemia appears to inhibit WNK activity, providing distal Na+ delivery that is used to drive K+ secretion.

The importance of this pathway is that it can explain the mechanism by which increased dietary K+ lowers blood pressure. Both reduced dietary salt intake and increased dietary K+ can reduce blood pressure in controlled settings, and recent large population studies have shown that increased dietary K+ and reduced Na-Cl intake not only lower blood pressure but reduce the incidence of cardiovascular disease and death.
DB-2-2: STARTING ANTIHYPERTENSIVE TREATMENT WITH COMBINATION THERAPY: CON SIDE OF THE ARGUMENT
Authors: STAESSEN JANA
Published: January 2023

The 2018 ESC/ESH and the 2020 ISH guidelines for the management of hypertension proposed that initial combination therapy with two antihypertensive agents in a single-pill combination (SPC) is preferred in most patients in need of blood-pressure (BP) lowering treatment and should replace the long-standing concept of starting treatment with a single agent, rotating through antihypertensive drug classes, and next moving towards combining drug classes. The 2019 Japanese guidelines took a more balanced approach in formulating their recommendation for the use of SPCs. The Japanese document states that when a systolic/diastolic BP decrease of 20/10 mmHg is targeted, combination therapy is an option to be considered in starting treatment. However, the Japanese guideline also recommended that if a drug shows only a weak depressor effect or is poorly tolerated, it must be replaced by another agent with a different mechanism of action, implying that starting with SPCs is not mandatory.

By moving SPCs forward as the initial BP lowering strategy, the ESC/ESH and ISH guideline committees overlooked several vested principles in hypertension management: (i) understanding the pathophysiology of hypertension; (ii) prioritizing evidence from randomized clinical trials above observational studies and expert opinion; and (iii) giving consideration to the cost-effectiveness of antihypertensive drug treatment and the sustainability of health care. This article addresses these points. Sources of information included: (i) guidelines issued by European, American, International, British and Japanese Expert Committees, published between 1999 and 2020; (ii) a PubMed search with as terms in the abstract or title hypertension combined with fixed combination OR hypertension combined with single and costs; (iii) the placebo-controlled trials of antihypertensive drug treatment; (iv) three randomized controlled trials of usual versus intensive BP control; and (v) the retail costs of antihypertensive drugs.

We propose that starting antihypertensive therapy in treatment-naive hypertensive patients might be based on a few simple principles. First, use antihypertensive drugs with different modes of action. Second, use antihypertensive agents with a long duration of action based on their molecular structure, so-called forgiving drugs, rather than extended-release dosage formulations. Third, titrate each drug to the highest dose that does not produce adverse effects. Fourth, include a thiazide in the drug combination. Finally, once the right combination has been found by rotating through and combining drug classes as well as the timing of dosing, stimulate adherence by reducing the pill load by prescribing of SPCs including 2 or 3 antihypertensive agents in adjustable doses.
S-02-4: BLOOD PRESSURE, ANTIHYPERTENSIVES AND DEMENTIA, AN INDIVIDUAL PATIENT DATA META-ANALYSIS
Authors: Peters Ruth , Anderson Craig
Published: January 2023

Background:

A large number of observational studies show links between hypertension or higher blood pressure (BP) in mid-life and an increased risk of later dementia. In late life, the evidence is more mixed with some studies indicating higher BP is associated with higher dementia risk and some finding U-shaped associations between BP and incident dementia in older age. The clinical trials of antihypertensives to lower BP have shown largely negative results when examining the relationship between antihypertensive use and incident dementia. However, the trials were designed to examine cardiovascular endpoints and several stopped early for cardiovascular benefit thus limiting their statistical power and ability to accrue dementia outcomes. To overcome some of these limitations a pooled individual patient data meta-analysis of five seminal double-blind placebo-controlled randomised trials was undertaken to better define the effects of BP lowering treatment for the prevention of dementia.

Methods:

The double-blind placebo-controlled randomised antihypertensive trials; Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), Hypertension in the Very Elderly Trial (HYVET), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), Systolic Hypertension in the Elderly Program (SHEP), and SYSTolic Hypertension in EURope Trial (SYST-EUR) were merged into a single database. Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, baseline Mini-Mental State Exam (MMSE) score and presence of prior stroke.

Results:

All trials were balanced across randomised groups. The combined sample was n = 28,008 recruited from 20 countries. Mean baseline age was 69.1 (Standard Deviation 9.3). Median follow-up 4.3 years. Incident dementia occurred in 2.9% and 3.3% of those in active and placebo groups, respectively. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age, sex, baseline systolic BP, baseline MMSE or prior stroke.

Discussion:

This is the first single-stage individual patient data meta-analysis from double-blind placebo-controlled clinical trials. It provides high-quality evidence to support the benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential benefit from antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia.
S-03-1: BRAIN IMAGING FOR THE MANAGEMENT OF HYPERTENSION
Authors: Tomimoto Hidekazu
Published: January 2023

Small vessels in the brain is susceptible especially for the effect of hypertension. Therefore, longstanding hypertension may induce cerebral small vessel disease (CSVD) which is designated as hypertensive CSVD. The patients with hypertensive CSVD may exhibit various types of lesions including lacunar infarction, white matter lesion, cerebral hemorrhage and microbleeds in brain magnetic resonance (MR) imaging. White matter lesions (WMLs) are one of the most representative lesions which are closely related to hypertension and aging. They are classified into periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH), and the former is more closely involved in cognitive decline than the latter. In the SPRINT MIND trial which examined the significance of intensive blood pressure control, WML volume increased by 0.28 cm3 for 4years in the intensive treatment group whereas by 0.92 cm3 in the standard treatment group, indicating 70% suppression of WML expansion. We quantitatively assessed WML volume in patients with vascular dementia and Alzheimer disease, and as expected, both PVH DWMH were significantly larger in vascular dementia than in Alzheimer disease. The mechanisms for CMBs are not fully understood but may be secondary to blood-brain barrier damages from long-standing hypertension, or alternatively, amyloid deposition in the tissue. In our previous study, we investigated degree of SVD changes using hypertensive arteriopathy SVD (HA SVD) and cerebral amyloid angiopathy SVD (CAA SVD) scores. With the analysis of SVD scores in 53 subjects with CMBs admixed with lobar and deep distributions, mixed CMBs were mainly caused by HA.

These neuroimaging markers are crucial for management of hypertension. Small subcortical stroke (SPS3) trial which enrolled patients with symptomatic lacunar infarctions, were divided into two groups: those with a systolic blood pressure target between 130 and 149 mm Hg and those with less than 130 mm Hg. There was no significant difference in the frequency of all strokes, the rate of intracerebral hemorrhage was significantly lower in the group with intensive blood pressure control. This SPS3 trial revealed that a systolic blood pressure target of less than 130 mm Hg is beneficial in reducing risk in lacunar stroke patients. Thus, we overview brain imaging markers in hypertensive patients and their significance for the management of SVD.
S-03-2: ASSOCIATIONS OF BRACHIAL-ANKLE PULSE WAVE VELOCITY WITH LEFT ATRIAL STIFFNESS AND LEFT ATRIAL PHASIC FUNCTION IN HYPERTENSION
Authors: Liu Yan , Fu Tingting , Pan Yu , Sun Qiaobing , Cong Tao , Jiang Yinong
Published: January 2023

Aims:

Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and arterial stiffness increased. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension.

Methods:

A total of 309 hypertensive patients enrolled and were divided into two groups based on baPWV [Group I, baPWV< 1517 (cm/s), n = 151; Group II, baPWV> 1517 (cm/s), n = 158]. Two dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e’ to

LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. Age, sex, and BMI were adjusted (Model 1), systolic blood pressure, Diabetes, HbA1c, LDL-C and eGFR were added (Model 2), then ACEIs/ARBs/ARNI treatment was added (Model 3), and last LVMI, LVEF, E/A ratio and LVGLS were added (Model 4).

Results:

LAS-S and LAS-E were significantly lower in Group II compared with Group I (P < 0.05 for both). LASI was significantly higher in Group II [0.36(0.25, 0.53)] compared with Group I [0.26(0.20, 0.36)] (P < 0.001). In multiple linear regression analysis, baPWV was associated with LASI, LAS-S, and LAS-E in Mode l, Model 2 and Model 3. However, after adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio and LVGLS), baPWV only remained significantly correlated with LASI in Model 4 (P = 0.002) for all patients and in both subgroups (Table). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.666 (95% CI: 0.605–0.726, P < 0.001). Furthermore, baPWV also had predictive values for LASI in age-specific and sex-specific subgroups, however, there were no significant differences between both sexes, or between younger (<50 years old) and older patients (>50 years old) (DeLong test: P > 0.05 for both).

Conclusion:

BaPWV was independently associated with LA stiffness, for all patients as well as in age-specific and sex-specific subgroups. BaPWV also had the predictive value for LA stiffness in hypertension. BaPWV maybe a convenient and useful screening tool for early detection of cardiac functional remodeling and interactions between cardiovascular abnormalities in hypertension.
S-03-4: RENAL IMAGING IN HYPERTENSION
Authors: Schmieder Roland Erich
Published: January 2023

In this lecture entitled “Renal Imaging in Hypertension” 2 aspects will be highlilighted:

1) The value of imaging the renal arteries and the kidneys morphology for the diagnosis of secondary hypertension and in particular renal artery stenosis. Moreover, the criteria, including imaging parameters for the decision to treat invasively renal artery stenosis or not will be outlined.

2) New technology developments are on the horizon that may enter in the near future the clinical field in order to improve the management of hypertensive patients. In particular, imaging the gidney and the renal perfusion by magnetresonanzimaging (MRI) will be discussed in detail, with its perspective for clinical research purposes as well as for clinicla apllication.

Overall, we can expect further development of imaging the kidneys that are most exciting.
S-05-1: ONSET OF LIFESTYLE-RELATED DISEASES AFTER THE GREAT EAST JAPAN EARTHQUAKE AMONG RESIDENTS IN FUKUSHIMA
Authors: Ohira Tetsuya
Published: January 2023

Due to the accident at the Fukushima Nuclear Power Plant (NPP) following the Great East Japan Earthquake on March 11, 2021, residents of the coastal areas of Fukushima Prefecture were forced to evacuate due to the effects of radiation and their lifestyles have changed dramatically. Therefore, we conducted the Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) to assess the health status of residents in the evacuation area and to prevent lifestyle-related diseases. First, to examine the short- to mid-term effects of the NPP accident, pre- and post-disaster data on health checkup of the evacuation area residents were retrospectively analyzed. Next, to examine the mid- to long-term effects of the NPP accident, we prospectively examined health examination data during the post-disaster period (fiscal year (FY) 2011–2017). The subjects were men and women living in 13 municipalities in the area surrounding the NPP in Fukushima Prefecture. We analyzed 27,486 men and women (12,432 men and 15,054 women) aged 20 years or older for whom health checkup data were available before and after the disaster, and found that the proportion of obese people and the prevalence of hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia, and atrial fibrillation were increased after the disaster (FY2011–2012), compared with those before the disaster (FY 2008–2010). This trend was more pronounced among residents who were forced to evacuate. The analysis of 27,536 people (12,254 men and 15,282 women) who could be followed for an average of 5.5 years from FY 2011 to FY 2017 showed that the proportion of obese people remained unchanged, while the proportion of people with liver dysfunction decreased. The prevalence of hypertension, dyslipidemia, and diabetes increased further. Furthermore, evacuees were shown to be at higher risk of developing diabetes, dyslipidemia, chronic kidney disease, hypertension, and hepatic dysfunction than non-evacuees. On the other hand, regular exercise was a significant preventing factor for liver dysfunction and dyslipidemia. Since residents in the evacuation areas, especially evacuees, continue to be at high risk of developing lifestyle-related diseases, especially cardiovascular diseases, it is necessary to management their health status over a long period of time and implement preventive measures against lifestyle-related diseases.
S-05-4: ENVIRONMENTAL POLLUTANTS AND BLOOD PRESSURE
Authors: Poulter Neil Reginald
Published: January 2023

Pollution via air, land and water was estimated to cause over nine million deaths globally in 2019.

The vast majority of these deaths and associated economic losses occur in LMICs.

It is estimated that almost seven million of these annual deaths are due to air pollution, which is increasing, due to an increase in outdoor sources whilst there has been a global decrease in household air pollution since 2000.

Of deaths caused by air pollution, it is estimated that approximately half are caused by cardiovascular disease (CVD) with about one third due to coronary heart disease and one fifth due to stroke.

One of the mechanisms whereby air pollution impacts adversely on CVD health is via raised blood pressure (BP). Lead pollution which is thought to cause almost one million deaths per year globally is also linked to increased BP levels and thereby to adverse CV outcomes.

This presentation will focus on air pollution and BP, since air pollution from combined indoor and outdoor sources is the major contributor to pollution-induced mortality.

Air pollution is cause by a mixture of particles or particulate matter (PM) and gaseous compounds which consist of nitrogen oxides.

The PM which consists of solid and liquid particles is classified by its aerodynamic diameter across a wide range and those with a diameter < 2.5pm (PM2.5) are commonly used to evaluate this form of pollution.

Short and longer-term exposures to elevated outdoor PM2.5 have been shown to be associated with higher BP and incident and prevalent hypertension. The mechanisms involved are thought to include damage to the vascular endothelium, via inflammatory and pro-oxidative reactions.

Few high-quality data linking different parameters of air pollution and effects on BP are available from around the world, particularly those areas worst affected by pollution.

Using the May Measurement Month (MMM) database, associations between BP and pollution are under investigation in retrospective and prospective studies.

In the retrospective studies data collected on the bespoke MMM app from 29 countries in MMM18 and MMM19 allow linkage between longitudinal and latitudinal coordinates of where BP was screened and PM2.5 pollution, based on data collected from ground monitors, satellite observations, meteorological data and land use.

In prospective studies from MMM21 data arising from 12 cities in the Philippines, Vietnam, Thailand and Indonesia, BP results and PM2.5 levels are in progress using linear mixed models to evaluate cross-sectional associations at the individual and screen-site levels.
S-06-5: HYPERTENSION MANAGEMENT IN PATIENTS WITH CARDIOVASCULAR DISEASE
Authors: Whelton Paul Kieran
Published: January 2023

High blood pressure is a major risk factor for new-onset and recurrent cardiovascular disease, including coronary heart disease, stroke, and heart failure. Most of the early event-based trials of antihypertensive medication were primarily secondary prevention studies. For example, in the first randomized controlled trial (RCT) of antihypertensive medication versus placebo, 62% of the 87 trial participants had CVD at baseline. In subsequent antihypertensive drug treatment trials, with much larger sample sizes, stratified analysis suggested similar treatment benefits in those with or without CVD at baseline. Further, individual trials and meta-analyses in participants with CVD but without hypertension demonstrated that antihypertensive drug therapy was effective for the prevention of recurrent CVD. In recent trials of more intensive BP reduction, stratified analysis identified no difference in treatment benefit between those with or without CVD at baseline or between those with a higher or lower level of CVD risk at baseline. Clinical practice guidelines generally recommend a final SBP target of less than 130 mm Hg in adults with CVD.

Diuretics, ACEI, ARB, and CCB are the best-proven drug classes for antihypertensive therapy in adults without a compelling indication for choice of a particular BP-lowering medication. However, specific combinations are recommended for the management of hypertension in adults with an underlying co-morbidity such as stable ischemic heart disease (SIHD), stroke, heart failure, or kidney disease. Beta-blockers are first-line agents in adults with SIHD, diuretics and CCBs are preferred agents in adults with prior stroke, and long-acting thiazide-like agents are especially useful in adults with heart failure. BP/hypertension clinical practice guidelines provide detailed recommendations for choice of agents and BP targets in adults with hypertension and co-morbidities, including various forms of CVD.
PS-BPB03-1: ASSOCIATION OF ANTIHYPERTENSIVE EFFECTS OF ESAXERENONE WITH THE INTERNAL SODIUM BALANCE IN DAHL SALT-SENSITIVE HYPERTENSIVE RATS
Authors: Rahman Asadur , Rahman Asasur , Kidoguchi Satoshi , Nourin Jahan , Fujisawa Yoshihide , Hossain Akram , Steeve Akumwami , Nakano Daisuke , Kobara Hideki , Masaki Tsutomu , Kitada Kento , Nishiyama Akira
Published: January 2023

Background:

We have recently shown that the nonsteroidal mineralocorticoid receptor blocker, esaxerenone elicits effective blood pressure reduction in Dahl salt-sensitive hypertensive (DSS) rats. Here, we investigated the potential contribution of alterations in sodium homeostasis to esaxerenone-induced blood pressure reduction.

Methods:

In the different experimental setups, we evaluated blood pressure by the radio-telemetry system and sodium homeostasis by an approach of sodium in (food intake) and out (urinary excretion) in a low-salt diet (LSD, 0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD with 0.001 % esaxerenone (w/w), and HSD with 0.05% furosemide fed DSS rats.

Results:

HSD-fed DSS rats exhibited a non-dipper type hypertension, while esaxerenone treatment but not furosemide significantly reduced the BP with a dipper pattern. The cumulative urinary sodium excretion was significantly elevated from day 6 onward both in esaxerenone- and furosemide-treated rats compared to their HSD-fed counterparts in the active period where a significant increase in Na+/K+ ratio was evident for only the esaxerenone treatment group. Sodium content in the skin, skinned carcass as well as total body level tended to reduce in esaxerenone-treated rats compared to the HSD-fed matching parts, while these values were not changed in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation revealed that esaxerenone but not furosemide treatment significantly attenuated glomerulosclerosis and tubulointerstitial fibrosis in HSD-fed DSS rats. Collectively, these findings suggest that esaxerenone-induced blood pressure reduction is associated with the body sodium homeostasis in salt-loaded DSS rats.
PS-BPB04-2: P2RX7 DEFICIENCY OR P2RX7 ANTAGONISM BLUNTS ANGIOTENSIN II-INDUCED HYPERTENSION, VASCULAR INJURY AND CD8+ T CELL ACTIVATION
Authors: Paradis Pierre , Shokoples Brandon , Berillo Olga , Comeau Kevin , Higaki Akinori , Caillon Antoine , Ferreira Nathanne S , Schiffrin Ernesto L
Published: January 2023

Objectives:

Innate and adaptive immune cells contribute to hypertension and end-organ damage. High blood pressure (BP) causes cardiovascular injury and the release of damage-associated molecule patterns such as adenosine triphosphate (ATP). ATP can bind to the purinergic receptor P2X7 (P2RX7) on innate immune cells triggering interleukin-1β; release, which drives further immune activation. Elevated plasma ATP levels was observed in hypertensive patients. We hypothesized that P2rx7 knockout or P2RX7 antagonism would blunt angiotensin II (AngII)-induced BP elevation and cardiovascular injury through decreased immune activation.

Design and method:

Ten-to-12-week-old male C57BL/6J wild-type (WT) and P2rx7-/-
mice were infused or not with AngII (1000 ng/kg/min) for 14 days. A second group of AngII-infused WT mice was also infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle. BP was determined by telemetry, plasma ATP using a bioluminescence assay, mesenteric artery function using pressurized myography, cardiac left ventricle (LV) function and mass by ultrasound and activated immune T cell infiltration in aortic perivascular adipose tissue (PVAT) by flow cytometry.

Results:

Plasma ATP was 2.2 fold higher in AngII-infused compared to sham-treated mice (P < 0.05). AngII-induced systolic BP elevation was reduced by P2rx7 deficiency (12 mm Hg, P < 0.05) or P2RX7 antagonism (27 mm Hg, P < 0.01). AngII induced a 26% decrease in LV fractional shortening (FS, P < 0.05) and a 1.5 fold increase in LV mass/body weight (BW) in WT mice (P < 0.001), which were exaggerated in P2rx7-/-
mice (FS: 38% lower and LVmass/BW: 1.14 fold higher, P < 0.05), but not in mice receiving AZ10606120. AngII treatment caused a 26% reduction in the dilatation response of mesenteric arteries to acetylcholine in WT mice (P < 0.05), but not in P2rx7-/-
or AZ10606120-treated mice. AngII promoted a 3.8 fold increase in CD69+CD8+ T cell infiltration in aortic PVAT of WT mice (P < 0.001), but not in P2rx7-/-
or AZ10606120-treated mice.

Conclusion:

P2rx7 knockout or antagonism attenuates AngII-induced BP elevation, vascular injury, and infiltration of activated CD8+ T cells into aortic PVAT. P2rx7 knockout exacerbated AngII-induced cardiac dysfunction and hypertrophy, whereas P2RX7 antagonism did not.
PS-BPB04-4: RENAL DENERVATION IMPROVES THE SURVIVAL RATE VIA A REDUCTION IN HEART RATE IN HIGH SALT-FED DAHL SALT-SENSITIVE RATS
Authors: Morisawa Norihiko , Kitada Kento , Fujisawa Yoshihide , Yamazaki Daisuke , Nakano Daisuke , Titze Jens , Nishiyama Akira
Published: January 2023

Objective:

We reported that high salt intake decreases heart rates via a reduction in renal sympathetic activity in normal Sprague Dawley rats to compensate for high salt-driven catabolism. We also revealed that Dahl salt-sensitive (DSS) rats cannot reduce heart rates during high salt intake because of the abnormal activation of renal sympathetic nerve activity. It is known that high heart rates are negatively associated with life span. Therefore, we hypothesized that renal denervation ontributes to the long life span in high salt-fed DSS rats.

Design and Method:

(Experiment 1) We performed renal denervation (n = 9) or sham operation (n = 9) on male DSS rats at 4 weeks of age. At the same time, we implanted a radiotelemetry transmitter for blood pressure measurements in the above rats (sham (n = 4), renal denervation (n = 5)). After two weeks of recovery, we started feeding them a 4% NaCl diet with 0.9% NaCl water to drink (HS). We observed the survival rates, blood pressure, and heart rates. (Experiment 2) Male, 4-week-old DSS rats were divided into three groups: i) sham operation + 0.2% NaCl diet with tap water to drink, ii) sham operation + HS, and iii) renal denervation + HS (n = 6 per group). At 2 weeks post-surgery, the rats were fed the respective diets for 6 weeks. We weekly measured systolic blood pressure by a tail-cuff method. After 6 weeks of observation, we harvested their skin and skinned carcass to measure their body.

Results:

The renal-denervated DSS rats showed a higher survival rate compared to the sham-operated DSS rats (p < 0.05). While renal denervation showed a decrease in heart rate, there was no significant decrease in mean arterial pressure throughout the experimental period. High salt intake significantly increased body Na content (mmol/g dry weight), whereas renal denervation did not alter body Na content in DSS rats.

Conclusion:

Renal denervation improved the survival rate in high salt-fed Dahl salt-sensitive rats, which may be mediated by a reduction in heart rate, but not body Na content nor blood pressure.
PS-BPB05-5: KIDNEY ENHANCEMENT OF ANGIOTENSIN II TYPE 1 RECEPTOR-ASSOCIATED PROTEIN SUPPRESSES KIDNEY INFLAMMATION IN A MOUSE MODEL OF ARISTOLOCHIC ACID NEPHROPATHY
Authors: Uehara Tatsuki , Urate Shingo , Wakui Hiromichi , Tsukamoto Shunichiro , Taguchi Shinya , Tanaka Shohei , Abe Eriko , Suzuki Toru , Azushima Kengo , Tamura Kouichi
Published: January 2023

Objective:

We previously reported that genetic knockdown of angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) exacerbated the aging-associated kidney tubulointerstitial fibrosis in mice (Uneda K, et al. J Am Heart Assoc 2017). However, little is known about whether enhancement of ATRAP expression could affect any pathological stimuli-induced kidney fibrosis and inflammation. Recently we proposed that aristolochic acid nephropathy (AAN) might be a useful model of kidney aging along with tubulointerstitial fibrosis (Urate S, et al. Int J Mol Sci 2021). The present study was designed to investigate the functional role of ATRAP in kidney fibrosis and inflammation, using ATRAP transgenic mice subjected to AAN.

Design and method:

We generated ATRAP transgenic (Tg19) mice under the control of chicken β;-actin promoter. (Wakui H, et al. Am J Physiol Renal Physiol 2010). The level of kidney ATRAP protein expression was about 4-fold higher in the Tg19 mice compared with wild-type littermate control (LC) mice. The Tg19 mice and LC mice were administered either vehicle or aristolochic acid (AA) (3 mg/kg) for 4 weeks, followed by a 4-week remodeling period. Kidney fibrosis was examined by histopathology and macrophage infiltration was determined by immunohistochemistry. Expression levels of genes associated with inflammation, fibrosis, and senescence were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immuno blot analyses.

Results:

AA administration provoked kidney fibrosis and inflammation accompanied by decreased kidney function. There were no significant differences in AA-induced kidney fibrosis estimated by qRT-PCR and histological analysis between the Tg19 and LC mice. Creatinine clearance was similarly decreased in the Tg19 and LC mice with AAN. However, AA-induced macrophage infiltration was significantly suppressed in the kidney of Tg19 mice compared with that of the LC mice. In addition, inflammation-, aging-, and oxidative stress-related genes (tumor necrosis factor-α, interleukin-1β;, cyclin-dependent kinase inhibitor 2A, wnt family member 9A, nicotinamide adenine dinucleotide phosphate oxidase 2) in response to AA administration were significantly suppressed in the kidney of the Tg19 mice compared with that of the LC mice.

Conclusion:

These results indicate that the enhancement of ATRAP expression suppresses kidney inflammation despite no evident effects on kidney fibrosis in a mouse model of AAN. ATRAP may be a therapeutic target for inflammation associated with CKD.
PS-BPB06-2: PIEZO2 EXPRESSION AND ITS ALTERATION BY MECHANICAL FORCES IN MOUSE MESANGIAL CELLS AND RENIN PRODUCING CELLS
Authors: Mochida Yuki , Ochiai Koji , Nagase Miki
Published: January 2023

The kidney plays a central role in body fluid homeostasis. Cells in the glomeruli and juxtaglomerular apparatus sense mechanical forces and modulate glomerular filtration and renin release. However, details of mechanosensory systems in these cells are unclear. Piezo2 is a recently identified mechanically activated ion channel found in various tissues, especially sensory neurons. Herein, we examined Piezo2 expression and regulation in mouse kidneys. RNAscope in situ hybridization revealed that Piezo2 expression was highly localized in mesangial cells and juxtaglomerular renin producing cells. Immunofluorescence assays detected GFP signals in mesangial cells and juxtaglomerular renin producing cells of Piezo2GFP reporter mice. Piezo2 transcripts were observed in the Foxd1 positive stromal progenitor cells of the metanephric mesenchyme in the developing mouse kidney, which are precursors of mesangial cells and renin producing cells. In a mouse model of dehydration, Piezo2 expression was downregulated in mesangial cells and upregulated in juxtaglomerular renin producing cells, along with the overproduction of renin and enlargement of the area of renin producing cells. Furthermore, the expression of the renin coding gene Ren1 was reduced by Piezo2 knockdown in cultured juxtaglomerular As4.1 cells under static and stretched conditions. These data suggest pivotal roles for Piezo2 in the regulation of glomerular filtration and body fluid balance.
PS-B12-2: ENDOTHELIN TYPE A RECEPTOR BLOCKADE ATTENUATES HEART FAILURE IN RATS WITH ANGIOTENSIN II-DEPENDENT HYPERTENSION.
Authors: Kala Petr , Gawrys Olga , Miklovic Matus , Vanourkova Zdenka , Skaroupkova Petra , Jichova Sarka , Sadowski Janusz , Jezierska Elzbieta Kompanowska , Walkowska Agnieszka , Veselka Josef , Taborsky Milos , Maxova Hana , Vaneckova Ivana , Cervenka Ludek
Published: January 2023

Objective:

Evaluation of the effects of endothelin type A (ETA) receptor blockade on the echocardiography, hemodynamic cardiac and renal parameters, and the course of high-output heart failure (HF) in rats with angiotensin II-dependent hypertension.

Design and Methods:

Eight-week-old male Ren-2 transgenic rats (TGR) were used as a model of angiotensin II-dependent hypertension. HF was induced by creating an aorto-caval fistula (ACF). Two weeks later, rats were divided into four groups: placebo (water) or three therapeutic groups (initial n minimum of 31 rats), and the treatment was initiated: in the first group, selective ETA receptor blockade was achieved by atrasentan, the second group received trandolapril, an angiotensin-converting enzyme inhibitor (ACEi), and the third was treated by combinational therapy (atrasentan + trandolapril), all in drinking water. The follow-up period was twenty weeks, then echocardiography, renal hemodynamics and albuminuria, invasive pressure-volume (P-V) analysis of left ventricle (LV), and organ weight measurement were done.

Results:

Eighteen days after creating ACF, untreated TGR began to die, and none was alive by day 79. Both atrasentan and trandolapril treatment improved the survival rate, ultimately to 56% (18 of 31 animals) and 69% (22 of 32 animals), respectively. Combined ACE and ETA receptor blockade improved the final survival rate to 52% (17 of 33 animals). The effects of the three treatment regimens on the survival rate did not significantly differ (Log-rank (Mantel-Cox) p = 0.345) (Figure 1, A). Untreated ACF TGR displayed marked renal dysfunction, cardiac hypertrophy, lung congestion, and impairment of LV contractility. None of the treatment regimens affected the progress of renal dysfunction, but they suppressed the albuminuria (Figure 1, B), development of cardiac hypertrophy and lung congestion and improved LV systolic function.

Conclusion:

The treatment with ETA receptor antagonist delays the onset of decompensation of volume-overload HF and improves the survival rate in hypertensive TGR similar to ACE inhibition.
PS-P12-8: THE PREVALENCE OF HYPERTENSION IN FACTORY EMPLOYEES, DETECTED DURING THE PERIODIC EXAMINATION AT THE FACTORY.
Authors: Soonthornvinit Warisa
Published: January 2023

Objective:

To describe the prevalence of hypertension in factory employees, detected during the periodic examination at the factory.

Design and method:

A descriptive study using the secondary data, a 2-year database (2020–2021) of 1,769 factory workers.

Results:

There were data of 1,769 workers from 11 different factories, 953 males (53.9%) and 816 females (46.1%). The majority age group was 40–49 years old (30.8%). Most of the workers were in a production line (61.6%).

Referring to the Thai Hypertension Society 2019, the prevalence of hypertension (BP > 149/90 mmHg) in factory employees was 28.4%.

Males (36.7%), age group of 50–59 years old (39.6%), vehicle control workers (42.2%), and mechanicians (40.5%) were detected with hypertension more than others.

Conclusions:

The prevalence of hypertension (BP > 149/90 mmHg) in factory employees detected during the periodic examination at the factory was 28.4%.
The role of Fusobacteria in oral cancer and immune evasion
Authors: Harrandah Amani M.
Published: January 2023

Purpose of review

There is growing evidence that suggests a possible role for bacteria in the progression of cancer. Fusobacteria have been detected in different types of cancers, including colorectal and oral cancers. Fusobacteria are common opportunistic oral bacteria known to cause various infections. In this review, we focus on the association between Fusobacteria and cancer, specifically oral cancer, and provide insight into the role of Fusobacteria in carcinogenesis and immune evasion.

Recent findings

Recently, it has been suggested that Fusobacteria are among the bacteria that contribute to the progression of cancer and might affect disease prognosis and treatment outcome. Moreover, Fusobacteria might alter tumor microenvironment and have an impact on tumor immune response. Thus, understanding the effect of Fusobacteria on cancer cells and tumor microenvironment is crucial to improve treatment outcome.

Summery

Recent evidences suggest that Fusobacteria not only have an impact on tumor progression, but might also affect tumor immune response. Moreover, Fusobacteria presence in the tumor microenvironment might have an impact on treatment outcome and might be used as a prognostic factor.