bluuebunny/crossref_metadata_2025 huggingface dataset:
Do simulated molecular clouds look like real ones?
Authors: Priestley F D , Clark P C , Whitworth A P
Published: January 2023

Simulations of molecular clouds often begin from highly idealized initial conditions, such as a uniform-density sphere with an artificially imposed turbulent velocity field. While the resulting structures may appear qualitatively similar to those detected in continuum and line observations, it is unclear whether they are genuinely representative of real molecular clouds. Recent observational work has discovered a tight, often close-to-linear relationship between the integrated intensity of molecular lines and the total column density of the cloud material. We combine magnetohydrodynamical simulations, time-dependent chemistry, and radiative transfer to produce synthetic molecular line observations of model clouds. We find similarly tight correlations between line intensity and column density to those observed, although the linear behaviour is only seen in isolated (as opposed to colliding) model clouds. This linear relationship is not due to optically thin emission; all lines investigated have high optical depths, and the increase in integrated intensity with column density is due to higher velocity dispersion along the line of sight. Overall, the idealized models commonly used in the literature appear to be reasonably accurate representations of real molecular clouds.
Holocene molluscan successions from southeastern Spain (Galera, Andalusia): a palaeoenvironmental framework and a palaeobiogeographic resource of the Granada UNESCO Geopark
Authors: Wackenheim Quentin , Richter Christiane , Limondin-Lozouet Nicole , Wolf Daniel , García-Tortosa Francisco Juan , Marzin Elisa , Hofmann Luise , Dabkowski Julie , Faust Dominik
Published: January 2023

In Spain, Holocene deposits are widespread, and although they have been extensively investigated by quaternarists for several decades, their malacological content has remained scarcely studied. In the framework of a German–French–Spanish collaboration, alluvial and tufa sequences in the Baza Basin, Andalusia, Spain are analysed with a multidisciplinary approach, including the analysis of the molluscan successions. Holocene fossil molluscs of the studied sequences reveal a rich assemblage of 53 species, among which 33 are terrestrial. Between 10,000 and 9,000 cal. yr BP, the Galera succession indicates strong river dynamics that prevented the establishment of adjacent terrestrial habitats. The Early to Middle Holocene transition reflects the continuity of humid environments. The Middle Holocene fauna reveals a decrease in humidity accompanied by slight evidence of drier habitats in the near periphery of the floodplain/tufa deposits from 5,900 cal. yr BP onwards. Late Holocene deposits (around 3,000 to 300 cal. yr BP) point to dry and open biotopes indicated by the appearance of xero-resistant and mesophilous gastropods. The palaeoenvironmental reconstruction inferred from the malacocenoses allows discussing local to regional responses of the malacofauna to environmental changes and is consistent with past regional environmental and climatic trends identified in southeastern Spain. The fossil record at Galera offers new evidence to question and clarify the modern range of endemic taxa whose distributions are fragmented. By following a ‘conservation paleobiology’ approach, the analysis of the mollusc fossil record at Galera provides (1) baselines to determine the natural variability of ecosystems and their response to environmental changes, (2) data to discuss and clarify species distribution evolution and (3) arguments to support conservation priorities.
Root PRR7 Improves the Accuracy of the Shoot Circadian Clock through Nutrient Transport
Authors: Uemoto Kyohei , Mori Fumito , Yamauchi Shota , Kubota Akane , Takahashi Nozomu , Egashira Haruki , Kunimoto Yumi , Araki Takashi , Takemiya Atsushi , Ito Hiroshi , Endo Motomu
Published: January 2023

The circadian clock allows plants to anticipate and adapt to periodic environmental changes. Organ- and tissue-specific properties of the circadian clock and shoot-to-root circadian signaling have been reported. While this long-distance signaling is thought to coordinate physiological functions across tissues, little is known about the feedback regulation of the root clock on the shoot clock in the hierarchical circadian network. Here, we show that the plant circadian clock conveys circadian information between shoots and roots through sucrose and K+. We also demonstrate that K+ transport from roots suppresses the variance of period length in shoots and then improves the accuracy of the shoot circadian clock. Sucrose measurements and qPCR showed that root sucrose accumulation was regulated by the circadian clock. Furthermore, root circadian clock genes, including PSEUDO-RESPONSE REGULATOR7 (PRR7), were regulated by sucrose, suggesting the involvement of sucrose from the shoot in the regulation of root clock gene expression. Therefore, we performed time-series measurements of xylem sap and micrografting experiments using prr7 mutants and showed that root PRR7 regulates K+ transport and suppresses variance of period length in the shoot. Our modeling analysis supports the idea that root-to-shoot signaling contributes to the precision of the shoot circadian clock. We performed micrografting experiments that illustrated how root PRR7 plays key roles in maintaining the accuracy of shoot circadian rhythms. We thus present a novel directional signaling pathway for circadian information from roots to shoots and propose that plants modulate physiological events in a timely manner through various timekeeping mechanisms.
NUCLEAR MEDICINE PROCEDURE VOLUME AND ESTIMATION OF COLLECTIVE EFFECTIVE DOSE IN TAMIL NADU TOWARDS THE ESTABLISHMENT OF DIAGNOSTIC REFERENCE LEVEL
Authors: Senthil Kumar M , Kumar C Senthil , Parmar R U , Velmurugan J
Published: January 2023

With an objective to establish adult diagnostic reference levels in the practice of nuclear medicine (NM) in the state of Tamil Nadu (TN), data on the predominant NM procedures carried out in the state are analyzed. In this study, data on total NM diagnostic procedures during the years 2015–19 along with patient-specific diagnostic NM procedure data for the period April–June 2021 from all centers in Tamil Nadu are collected and analyzed using SPSS statistical software. Nine predominant types of NM scans are analyzed. Collective effective dose from NM scans and per capita dose for the TN population are estimated. The 75th percentile of the distribution and average administered activity (AAA) has been derived and local reference levels are reported. Based on the statistical analysis, it is observed that the whole-body positron emission tomography (PET), renal diethylenetriamine pentaacetate (DTPA) scan, bone methylene diphosphonate (MDP) scan, iodine-131 whole body scan, thyroid studies using Technetium per technetate, renal dimercaptosuccinic acid (DMSA), myocardial perfusion methoxyisobutyl isonitrile sestamibi (MIBI), mebrofenin, Galium-68 prostate-specific membrane antigen (PSMA) are the most common procedure covering >90% of the practices carried out. The collective effective dose is 410 man-Sv in the year 2019, leading to a mean effective dose of 0.006 mSv per capita of the TN state population. The 75th percentile of the distribution of AA is slightly higher than diagnostic reference level (DRL) as compared with Australian DRL (310 MBq). It is also observed that F-18 PET procedures are primarily responsible for most of the collective effective dose, local DRL is 316 MBq and it is important to establish national DRLs for NM diagnostic scans to optimize the NM examinations.
Penile metastasis from prostate cancer misdiagnosed as Peyronie disease: a case report
Authors: Dai Yu , Shi Bao-Lei , Zhang Jie , Liu Shuang-Ning , Jia Ya-Tao
Published: January 2023

Introduction

Penile metastases from prostate cancer are rare, and patients’ prognosis and survival rates are low. Conservative treatment is usually recommended for such patients with an emphasis on improving their quality of life.

Aims

The aims were to raise awareness of penile metastasis from prostate cancer and Peyronie disease among physicians and other health care professionals, as well as to provide a useful experience for future diagnosis and treatment.

Methods

The current case report is based on patient self-report and a literature review. Written informed consent was obtained from the patient.

Results

We report the case of a 68-year-old man who was admitted with a complaint of urinary retention. Preoperative examination and ancillary tests showed a 2.0-cm-long hard nodule palpable on the dorsal aspect of the penile root, which was misdiagnosed as Peyronie disease. However, a biopsy of the penile scleroma was performed, and the final pathology finding confirmed the diagnosis of penile metastasis from prostate cancer. The patient opted for continuous androgen deprivation therapy (abiraterone) and systemic chemotherapy (docetaxel and cisplatin). He was treated for 2 cycles and had no specific discomfort during chemotherapy, except for significant gastrointestinal reactions, hypocellularity, and hair loss symptoms.

Conclusion

This report describes a rare case of penile metastasis from prostate cancer, which was initially misdiagnosed as Peyronie disease, indicating that clinicians need to improve their understanding and discrimination of this disease.
Cluster-randomized controlled trial of intermittent preventive treatment in infancy using sulfadoxine–pyrimethamine (SP-IPTi): a pilot study in Nigeria
Authors: Adeleke Olumide Thomas , Oyenuga Abayomi , Slusher Tina M , Gbadero Daniel A
Published: January 2023

Background

Malaria kills a child in sub-Saharan Africa every 2 min despite widely available interventions including intermittent preventive treatment in infants (IPTi). Since 2010, when World Health Organization (WHO) recommended IPTi, no country has implemented it. To our knowledge, no IPTi study has been conducted in Nigeria. Considering severity of malaria in infancy and urgency to improve malaria prevention, we proposed a study to investigate the efficacy of this intervention in reducing malarial morbidity and mortality.

Objective(s)

The aim of this was to determine the safety and efficacy of SP-IPTi in reducing the prevalence of asymptomatic malaria parasitemia and malarial-associated hospital admissions.

Methods

We performed a cluster-randomized controlled trial in 1379 infants. SP was administered alongside routine vaccinations in immunization centers randomized to intervention groups. Infants in control groups received only routine vaccines. Malarial ‘morbidity and adverse events were monitored through passive case-detection and cross-sectional surveys’.

Results

SP-IPTi was safe. There was no statistically significant difference in terms of risks of asymptomatic parasitemia at 9 months, fever or hospitalization between our control and intervention groups.

Conclusions

Our study demonstrated that SP-IPTi had no benefit but was well tolerated. WHO and some researchers have also reported declining efficacy of SP, due to increasing drug resistance.
Effects of Metconazole + Prothioconazole, Pydiflumetofen + Propiconazole, and Variety Resistance on Fusarium Head Blight and Yield in Hard Red Spring Wheat
Authors: Lux LeAnn , Halvorson Jessica , Hansen Bryan , Meyer Scott , Carruth Dave , Fitterer Scott , Friskop Andrew
Published: January 2023

Fusarium head blight (FHB), caused primarily by Fusarium graminearum (Schwabe), is one of the most significant diseases of hard red spring wheat (HRSW) in North Dakota. Implementing integrated management practices such as host resistance and fungicides can be used to manage FHB and the associated mycotoxin deoxynivalenol (DON). However, depending on the production year in North Dakota, both management tools might not be needed for FHB. The objective of this research was to evaluate fungicide premixes and varietal resistance on suppression of FHB, suppression of DON, and economic response in diverse FHB environments in dryland HRSW. Seven field experiments were conducted at dryland locations from 2019 to 2021. Two HRSW varieties, WB-Mayville (susceptible) and ND-VitPro (moderately resistant) served as the main plots, and seven fungicide treatments, including a nontreated control, served as the subplots. Based on disease levels and local weather data (relative humidity, rainfall, and temperature), field experiments were categorized into four FHB management environments (high, moderate, low, and no disease) to assess the effectiveness of management tools in field situations faced by HRSW growers. The fungicide premixture treatments of metconazole + prothioconazole and pydiflumetofen + propiconazole provided similar or better suppression of FHB and DON when compared with FHB fungicide standards. The results suggest that the use of fungicides on a moderately resistant variety provided a more favorable economic response when compared with their use on a susceptible variety in moderate and low FHB environments. The results from this study will help guide FHB management decisions in dryland HRSW.
PL-3: RECENT PROGRESS IN IPS CELL RESEARCH AND APPLICATION
Authors: Yamanaka Shinya
Published: January 2023

Induced pluripotent stem cells (iPSCs) can proliferate almost indefinitely and differentiate into multiple lineages, giving them wide medical applications. As a result, they are being used for new cell-based therapies, disease models, and drug development around the world.

In our basic research, we are focusing on the mechanisms of protein translational regulation in the proliferation and differentiation of iPSCs. We have previously reported that the translation regulator NAT1 is essential for the self-renewal and neuronal differentiation potential of hiPSCs, which is a “Bench to Bedside” activity for the medical application of iPSCs.

As translational research, we are proceeding with an iPSC stock project in which clinical-grade iPSC clones are being established from healthy donors with homologous HLA haplotypes to lower the risk of transplant rejection. We started distributing the iPSC stock to domestic and overseas institutions, and related clinical studies have begun for age-related macular degeneration (AMD), Parkinson's disease, corneal epithelial stem cell deficiency, and other diseases, giving expectation that iPSC-based regenerative medicine will be widely used in the future. However, donors with HLA homozygous are rare. Genome editing technology could be used to reduce the transplant-rejection risk. Indeed, we reported HLA gene-edited iPSCs that could expand the range of patients who benefit from iPSC therapies faster than the homologous HLA haplotype strategy. This technology also has the potential to prevent or treat genetic diseases and gives great hope to patients.

Other applications of iPSCs are drug screening, toxicity studies, and disease modeling. In 2017, a new drug screening system using iPS cells for fibrodysplasia ossificans progressiva (FOP) was reported, revealing one drug candidate, Rapamycin, which is now undergoing a clinical trial to treat FOP patients. Additionally, Bosutinib, a drug for leukemia was revealed to be efficacious for amyotrophic lateral sclerosis (ALS) using a disease-specific iPSC model. Accordingly, we initiated a Phase 1 clinical trial of Bosutinib to treat ALS at Kyoto University Hospital and other centers in 2019 and began Phase 2 clinical trials in April 2022. Furthermore, we initiated a Phase I clinical trial of Bromocriptine to treat Alzheimer's disease at Kyoto University Hospital in June 2020. Thus, drug repurposing using iPS cells is progressing at an accelerated pace.

Over the past decade, iPSC research has made great progress, moving toward innovative therapeutics for people with intractable diseases by the application of new findings from basic science and reverse translation from clinics.
SP-4: FUTURE BLOOD PRESSURE RESEARCH
Authors: Nishiyama Akira
Published: January 2023

How is our body's blood pressure regulated? What exactly is the specific mechanism by which hypertension develops? To date, there is no evidence to answer these questions. Therefore, there is no fundamental cure for hypertension, and we must continue to take blood pressure-lowering drugs for the rest of our lives. So, why do we need blood pressure in the first place? It is because the heart needs to pump blood throughout the body to systemically supply necessary oxygen, nutrients, and hormones. We land animals have acquired high blood pressure during the course of evolution, enabling us to perform at a high level even in harsh environments. Humans, in particular, are able to maintain high blood pressure levels even when walking on two legs, allowing to defy gravity and deliver sufficient blood to the brain. This made humans the only high-performance creature capable of using both hands and the only one capable of running marathon distances. However, in the age of plenty, high blood pressure has become increasingly damaging to our bodies. Furthermore, in the future, when we have to live in space, underwater, or other spaces with little gravity, too high blood pressure will have an even more detrimental effect on our bodies. Thus, the development of blood pressure research is essential for the further evolution of humankind, since humans need to constantly optimize their blood pressure to adapt to changes in the environment.
S-04-1: CURRENT EVIDENCE AND ISSUES ON AOBP FROM JAPAN
Authors: Asayama Kei
Published: January 2023

The potential ability of unattended office blood pressure (AOBP) has been acknowledged worldwide, including Japan, although much resource consumption makes it less feasible to use AOBP in clinical practice. We reported that the three consecutive AOBP measurement values in each patient were almost identical, with high correlations (r ≥ 0.90), and the AOBP and conventional attended office blood pressure were moderate to highly correlated. We therefore interpret that AOBP can be an alternative that is more stable than the conventional attended blood pressure value despite with the average shifted to some extent, e.g., 10.4/4.2 mmHg based on the same study. In contrast, there is a fundamental discrepancy between the similarity in average values and the poor agreement in individuals when we compare AOBP versus self-measured home blood pressure, as the systolic blood pressure difference was 0.9 mmHg with a 95% agreement limit was -34.0 to + 35.8 mmHg. The vast wide range of difference indicates that we cannot estimate home as well as ambulatory blood pressure values by AOBP measurements in each patient, and vice versa.

AOBP has another advantage regarding the elimination of white-coat effect by the presence of medical staff. Nevertheless, because AOBP measurement is performed at a clinic or in a screening setting where participants cannot be relaxed like at their own home, such a clinic effect still affects AOBP readings. In this session, the current evidence on AOBP based on our Japanese studies and others will be summarized and issues which remain to be investigated for the assessment of a variety of blood pressure conditions, unattended and attended office, and out-of-office blood pressures will be discussed.
S-07-7: ANGIOTENSIN, VASCULAR AGING AND HYPERTENSION
Authors: Touyz Rhian
Published: January 2023

Aging is a major non-modifiable risk factor underlying hypertension and associated cardiovascular disease. With aging, the vasculature undergoes structural, functional and mechanical alterations characterized by endothelial dysfunction, media thickening, reduced distensibility, and arterial stiffening. Many of these processes are associated with activation of the renin angiotensin aldosterone system (RAAS), which is characteristically associated with the pathophysiology of hypertension. In particular Ang II, through the AT1 receptor, and aldosterone through the mineralocorticoid receptor, activate pro-inflammatory and pro-fibrotic signaling pathways that lead to vascular fibrosis, extracellular matrix (ECM) deposition, arterial remodelling, perivascular inflammation and hyperreactivity. These processes are also associated with aging and are amplified by hypertension. Molecular mechanisms underlying these events include increased expression and activation of matrix metalloproteinases, activation of transforming growth factor1/SMAD signalling, upregulation of galectin-3, activation of aging signaling pathways, eg p66Shc, c-Src, and oxidative stress. Fundamental to these processes is phenotypic switching of vascular smooth muscle cells from a contractile to de-differentiated state. This involves epigenetic changes and alterations in the vascular proteome. Complex interplay between the “aging process” and prohypertensive factors, including Ang II and aldosterone, result in accelerated vascular remodelling and fibrosis and increased arterial stiffness, which is typically observed in hypertension. Because the vascular phenotype in a young hypertensive individual resembles that of an elderly otherwise healthy individual, the notion of “early” or “premature” vascular aging is frequently used to describe hypertension-associated vascular disease. This presentation discusses the vascular phenotype in aging and hypertension and the role of the RAAS. In addition novel molecular mechanisms, focusing on oxidative stress and the vascular proteome will be highlighted.
S-12-6: CARDIOPROTECTIVE EFFECTS OF FINERENONE ASSOCIATED WITH THE SUPPRESSION OF MYOCARDIAL SODIUM ACCUMULATION IN ALDOSTERONE-INDUCED RATS
Authors: RAHMAN ASADUR MD , Sawano Tatsuya , Kitada Kento , Nakano Daisuke , Morikawa Takashi , Imamura Takeshi , Ohsaki Hiroyuki , Konishi Yoshio , Nishiyama Akira
Published: January 2023

Recent clinical studies have indicated that the nonsteroidal mineralocorticoid receptor (MR) antagonist, finerenone, elicits significant cardioprotective effects. However, its precise mechanism is not clear. Here, we aimed to test the hypothesis that cardioprotective effects of finerenone is associated with sodium and macrophage accumulations in heart tissues. Effects of finerenone (10 mg/kg body weight by oral gavage) on myocardial injury and sodium accumulation were examined in Sprague-Dawley rats with chronic aldosterone infusion (0.75 μg/hr) and salt loading through drinking water (1% NaCl). In a survival study, we have started treatment from 6 weeks of age and found that all aldosterone-infused rats died within 30 days infusion, while all those concomitantly treated with finerenone survived until 42 days. In other experiments, we started all treatments from 7 weeks of age, and echocardiography and gene expression analyses revealed an adverse cardiac remodeling as well as diastolic dysfunction with preserved ejection fraction in rats with salt loading and aldosterone infusion for 4 weeks. Notably, finerenone treatment completely prevented the cardiac dysfunction with the improved cardiac remodeling in these rats. Furthermore, Na+ content as well as Na+/K+ ratio in left ventricular tissues were markedly elevated in salt-loaded aldosterone-infused rats, but significantly reduced in rats with concomitant finerenone treatment. Moreover, gene expression of F4/80 (a macrophage marker) was significantly reduced by finerenone treatment. These data indicate that finerenone has the potential to mitigate cardiac diastolic dysfunction in salt-loaded and aldosterone-infused rats by suppressing sodium accumulation in left ventricular tissues. These effects of finerenone may attenuate a subsequent inflammation by macrophages and adverse cardiovascular remodeling.
S-13-1: MANAGEMENT OF ADRENAL INCIDENTALOMAS
Authors: Prete Alessandro
Published: January 2023

Adrenal tumours are commonly discovered incidentally on cross-sectional abdominal imaging performed for reasons other than adrenal mass. Incidence of adrenal tumours increased 10-fold in the past 2 decades, with most diagnosed in older adults. In any patient with a newly discovered adrenal mass, determining whether the adrenal mass is malignant and whether it is hormonally active is equally important to guide the best management. Malignancy is diagnosed in 5% to 8% of patients with adrenal tumours, with a higher risk in young patients, if history of extra-adrenal malignancy, in those with large adrenal tumours with indeterminate imaging characteristics, and in bilateral adrenal tumours. Although overt hormone excess is uncommon in adrenal incidentalomas, mild autonomous cortisol secretion can be diagnosed in 30% to 50% of patients. Because autonomous cortisol secretion is associated with increased cardiovascular morbidity and metabolic abnormalities, all patients with adrenal incidentalomas require workup with dexamethasone suppression test. Management of adrenal tumours varies based on aetiology, associated comorbidities, and patient preference. This presentation will focus on the current evidence on the diagnosis and evaluation of patients with adrenal mass, including the management of the most common aetiologies of adrenal incidentalomas.
S-14-5: JSH GUIDELINE FOR THE MANAGEMENT OF HYPERTENSION 2019 (JSH2019) ∼ CONCEPT AND SUBSEQUENT CHALLENGES ∼
Authors: Hirawa Nobuhito
Published: January 2023

Hypertension Treatment Guidelines 2019 (JSH2019) is based on JSH2014 and complies with Minds’ clinical practice guideline creation manual, and adopts a policy of adding new evidence. For this reason, we have newly ‘ extracted clinical issues, raised them as clinical questions (CQ), conducted a comprehensive systematic review (SR), created a body of evidence, and made recommendations.’. Since conducting SR appropriately requires a huge amount of labor, we decided to form an SR team centered on young members of the Society and proceed with the work while receiving guidance from a support team of epidemiological experts. In particular, we hope that SR will lead to the development of young people who will lead the future, and we also aimed to submit the results of SR to Hypertens Res. In the end, we were able to create 17 CQs. Furthermore, in JSH2019, we calculated the absolute risk of CVD in Japanese people based on the JALS and Hisayama-town studies, and used it for risk stratification. Hypertension was defined as a blood pressure value of 140/90 mmHg or higher for which the efficacy of antihypertensive drugs has been proven in patients who are not at high risk. Evidence was also emphasized for blood pressure reduction goals. To the low-risk and the moderate-risk patients with elevated blood pressure, we recommended to achieve the target blood pressure control by modifying lifestyle habits without using antihypertensive drugs. We also asked patient groups to review the guidelines, aiming to reflect the values and wishes of patients.

As we approach the third year since the publication of JSH2019, we would like to consider the remaining issues. There are still many patients whose blood pressure is not properly controlled, and many of whom are not aware that they have hypertension. Improvements in blood pressure control among the population are desired through countermeasures against clinical inertia and population tactics. This guideline was created with the aim of preventing CVD and improving patient prognosis, as described above. However, in a super-aging society, patients’ hopes are not necessarily to improve only the prognosis of life. There are many issues that need to be addressed in future guideline revisions, such as reconsidering recommendations for the elderly by appropriately understanding the ‘values and wishes of patients’ according to their age.
S-15-2: COMMUNITY-BASED APPROACHES TO PREVENTION AND MANAGEMENT OF HYPERTENSION
Authors: Ferdinand Keith C
Published: January 2023

There are multiple level factors that contribute to hypertension prevalence and control across various racial/ethnic populations. Hypertension rates in non-Hispanic Black (African American) adults in the USA are among the highest globally, impacted by the social determinants of health. Clinical approaches include team-based care, encouraging self-measured blood pressure, and strengthening community-clinical linkages. Prevention of new-onset hypertension and complications has been clearly demonstrated with community-level NaCl substitution in China and Peru. In the USA, Black population treatment approaches as community interventions include early initiatives from the Association of Black Cardiologists and the Healthy Heart Community Prevention Project (HHCPP) in New Orleans. The HHCPP was one of the early adopters of using barbers and hair stylists as hypertension control centers, working with faith-based institutions, and doing community education and outreach. Evidence-based approaches, now proven to be effective, include the faith-based treatment program for hypertension in New York, NY and a very successful in cluster-randomized trial demonstrating hypertension control in Black barbershops in Los Angeles, CA. The positive components of the Los Angeles barbershop intervention include trusted site of blood pressure intervention, physician-pharmacist collaboration, and effective anti-hypertensive medication including initial two drug protocol with amlodipine and a long-acting RAS blocker, and the appropriate use of aldosterone antagonists. Ongoing research include a small pilot study, simple text messaging and social support in New Orleans for medication adherence which will be reported at the AHA 2022 scientific sessions, and a large church-based health intervention study addressing primary prevention, including hypertension in New Orleans among 42 selected African American churches using community health workers in a combination of exercise weight-loss programs, self-monitoring blood pressure, glucose, and physical activity, and group education centers. In the USA, the American Heart Association in conjunction with the US Department of Health and Human services have initiated a national hypertension control initiative. Overarching strategies include patient and public education, community outreach and integration, and healthcare organization including provider and clinician training, as well as management evaluation of the project. This national program will engage community partners with federal health centers. In conclusion, hypertension can be controlled with evidence-based medicines, not only in clinical settings, but also with interventions in the community environment. Therapeutic lifestyle and evidence-based pharmacotherapy along with self-monitored blood pressure can lead to blood pressure control, especially in racial/ethnic populations.
S-15-3: COST-EFFECTIVENESS OF A FULL SCOPE OF PHARMACIST CARE FOR HYPERTENSION IN AUSTRALIA
Authors: Schutte Aletta E , Schlaich Markus P , Johnston Karissa , Marra Carlo A , Tsuyuki Ross T
Published: January 2023

Hypertension is the single most important cause of premature morbidity and mortality in the world. Over half of all heart disease and stroke are attributable to hypertension, which is associated with approximately 10% of direct medical costs globally. Clinical trial evidence has conclusively demonstrated that pharmacist care, including patient education, consultation, and/or prescribing, significantly reduces blood pressure, including a Canadian randomised trial, RxACTION, which demonstrated an 18.3 mmHg reduction in systolic blood pressure (SBP) with pharmacist prescribing and care.

Objective:

To evaluate the economic impact of pharmacist management of hypertension in an Australian setting.

Methods:

A Markov cost effectiveness model was developed to extrapolate potential differences in long-term cardiovascular and renal disease outcomes, using Framingham risk equations and other published risk equations. We assumed an absolute reduction of systolic blood pressure of 18.3 mmHg (from the RxACTION trial). The model incorporated health outcomes, costs, and quality of life to estimate an overall incremental cost effectiveness ratio. Costs considered included direct medical costs as well as the costs associated with implementing the pharmacist intervention strategy.

Results:

For a SBP reduction of 18.3 mmHg, the estimated impact is 0.22 fewer cardiovascular events per person, and, discounted at 5% per year: 0.2 additional life years, 0.3 additional quality-adjusted life years, and $AU 5,348 cost savings over a lifetime per person. As such, pharmacist care in hypertension is economically dominant, i.e., both more effective and cost saving compared to usual care. At the population level, it has been reported that 34% of Australian adults have hypertension, of whom 68% are not optimally controlled. If 50% of poorly controlled hypertensives could access a full scope of pharmacist care, it is estimated that this would result in 2.1 million life years saved, and a cost saving of $AU 31.1 billion over a 30-year time horizon.

Across a range of one way and probabilistic sensitivity analyses of key parameters and assumptions, pharmacist intervention remained both effective and cost saving, indicating robustness of the model.

Conclusion:

Pharmacist care, including prescribing, when added to usual care by general practitioners, would lead to better BP outcomes and a net cost saving of over $AU 30 billion. If implemented, this would have important public health implications.
S-16-6: NATRIURETIC PEPTIDES AND HUMORAL FACTORS IN CARDIORENAL SYNDROME AND RESISTANT HYPERTENSION
Authors: Mukoyama Masashi
Published: January 2023

Hypertension is one of the strongest and modifiable risk factors for cardiovascular disease, and a variety of antihypertensive agents and treatment modalities have been developed in these 6 decades. In Japan, however, among the patients with hypertension, ∼75% fail to reach an optimal goal of target blood pressure, and 10–15% of the patients are referred to as resistant hypertension. There are a number of factors for resistant hypertension; especially, the prevalence of resistant hypertension is reported to be 2–3 times higher in patients with chronic kidney disease (CKD) than in the general hypertensive population. CKD has become a major challenge to public health all over the world, and one of the reasons for increased morbidity should be the increasing prevalence of cardiometabolic (or metabolic kidney) disease including diabetic kidney disease. Considering them, novel therapeutic strategies are eagerly being sought.

We have studied the roles of vasoactive hormones, such as natriuretic peptides and aldosterone, and local humoral regulators in the pathophysiology of CKD. We have especially focused on metabolic renal disease, including diabetic nephropathy, nephrosclerosis, and renal fibrosis as their common consequence. Using genetically engineered mouse models, we demonstrated the renoprotective role of natriuretic peptides (ANP, BNP) against diabetic nephropathy, immune-mediated renal injury as well as renal fibrosis by subtotal renal ablation. Furthermore, using natriuretic peptide receptor (GC-A)-deficient mice coupled with aldosterone-induced renal injury, we found a renoprotective role of natriuretic peptides on podocytes independent of their antihypertensive action, by inhibiting the local RAS-MAPK-cytokine cascade activation. From recent GWAS analyses, gene polymorphisms related to the natriuretic peptide system are found to be strongly associated with hypertension and cardiovascular disease, suggesting their critical role in cardiovascular homeostasis and blood pressure control. Angiotensin receptor-neprilysin inhibitor (ARNI) is a new class of anti-hypertensive agents characterized by its dual action with renin-angiotensin system blockade and inhibition of natriuretic peptide degradation. In recent clinical trials, ARNI has been shown to have significant cardio-renoprotective effects with a potent antihypertensive property. These findings together could show potential molecular targets, providing a promise for novel therapeutic approaches against CKD with resistant hypertension, metabolic renal disease and related cardiovascular complications.
S-17-5: EFFECT OF MINERALOCORTICOID RECEPTOR BLOCKER, ESAXERENONE, ON HOME BLOOD PRESSURE AND ALBUMINURIA IN JAPANESE HYPERTENSIVE PATIENTS WITH DKD (EX-DKD STUDY)
Authors: Uchida Haruhito A , Nakajima Hirofumi , Hashimoto Masami , Nakamura Akihiko , Nunoue Tomokazu , Murakami Kazuharu , Hosoya Takeshi , Komoto Kiichi , Taguchi Takashi , Akasaka Takaaki , Shiosakai Kazuhito , Sugimoto Kotaro , Wada Jun
Published: January 2023

Objective:

To investigate the effect of esaxerenone on home blood pressure (BP) and albuminuria in Japanese hypertensive patients with diabetic kidney disease (DKD) who had an inadequate response to BP-lowering treatment with a renin angiotensin system (RAS) inhibitor or a RAS inhibitor plus a calcium channel blocker (CCB).

Design and method:

The EX-DKD study (jRCTs061190027) was a multicenter, open-label study conducted in Japan. The study enrolled hypertensive patients with DKD who had previously received a RAS inhibitor or a RAS inhibitor plus CCB for < 12 weeks, and had sitting office systolic BP (SBP) 130 to < 180 mmHg and/or diastolic BP (DBP) 80 to < 110 mmHg, UACR < 1000 mg/g creatinine, and eGFRcreat 30 to < 60 mL/min/1.73m2 at baseline. Based on baseline UACR, the patients were divided into 3 subcohorts: UACR < 30, 30 to < 300, and 300 to < 1000 mg/g creatinine. Esaxerenone was incrementally dosed for 12 weeks: 1.25, 2.5, and 5 mg/day at the start of treatment, Week4, and Week8, respectively, based on each patient's condition. The primary efficacy endpoint was change in morning home SBP/DBP from baseline to end of treatment (EOT). Secondary endpoints included the proportion of patients achieving target BP at Week12, change in UACR from baseline to EOT, and safety (including serum potassium level).

Results:

The baseline characteristics of the overall study population (n = 109) were mean age, 72.6 years; male, 54.1%; morning home SBP/DBP, 135.6/75.9 mmHg; UACR < 30, 30 to < 300, and 300 to < 1000 mg/g creatinine, 41.3%, 37.6%, and 21.1%, respectively; eGFRcreat, 49.4 mL/min/1.73m2; RAS inhibitor, 33.0%; RAS inhibitor plus CCB, 67.0%. Morning home SBP/DBP decreased significantly from baseline to EOT in the total population (-11.6/-5.2 mmHg, both p < 0.001) and all UACR subcohorts (all p < 0.001). Similar results were obtained for bedtime home and office BP. At Week12, 38.5% of the total population had achieved target morning home BP. UACR improved significantly from baseline to EOT in the total population and UACR subcohorts; the overall percentage change was -50.9% (p < 0.001). Incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 23.2% and 7.1%, respectively. The percentage of patients with serum potassium <5.5 mEq/L during the study period was 2.7%, and no patients had serum potassium < 6.0 mEq/L.

Conclusions:

Esaxerenone significantly reduced morning home BP as well as bedtime home and office BP and significantly halved albuminuria in Japanese hypertensive patients with DKD. The effects were consistent regardless of their UACR severity without clinically relevant serum potassium elevation.
S-20-4: HYPERTENSION AND CARDIOVASCULAR DISEASE IN ASIA
Authors: Castillo Rafael Ricafranca
Published: January 2023

Being the most populous continent in the world, consisting of around 60% of the global population, Asia shoulders a big brunt of the hypertension and cardiovascular disease (CVD) burden in the world. Just as it is in the rest of world, hypertension remains a major modifiable risk factor in Asia for stroke, myocardial infarction, heart failure, atrial fibrillation, and peripheral arterial disease; and it is a dominant risk factor implicated for cardiovascular deaths causing premature death in the region. There is generally a stronger association between elevated blood pressure (BP) and stroke than with coronary artery disease (CAD), although CAD is reported as the most dominant cause of CVD deaths in Central, Western, and Southern Asia, while stroke deaths is more common than CAD deaths in Eastern and Southeastern Asia.

Of the estimated 1.13 billion people worldwide with elevated BP, around 66% live in low and middle income countries, which consist the majority of countries in Asia. In Southeast Asia (SEA), the prevalence of hypertension in the adult population is nearing 35%, and to this has been attributed the close to 1.5 million deaths in the region annually.

Hypertension awareness, treatment and control remain a challenge in Asia. Awareness level is less than 50% in most countries in Asia, though it is higher (56 70%) in the higher income countries in the region. Treatment rates are generally 25% to 30% of the hypertensive population, but control rates to BP levels below 140/90 mmHg, are still dismally low.

The comparatively high dietary salt intake in the region, aggravating the salt sensitive phenotype characterizing Asian hypertension is implicated as a significant risk factor leading to poor hypertension control and a relatively increased rates of strokes in the region. Salt intake ranges from 10to17 grams a day, which is 2to3 times higher compared to the 5 grams (approximately 2 grams of sodium) recommended daily salt consumption by the World Health Organization.

Because of the socioeconomic, educational and cultural heterogeneity of the countries comprising Asia, the region appears to be in different transition stages of the CVD epidemic. This highlights the challenge in mapping out a one size fits all strategy in curbing hypertension and CVD in Asia. Individualized prevention and treatment strategies factoring the differing capacities for management, prevalence of unhealthy diet especially increased salt intake, smoking, obesity, hypertension, dyslipidemia, and diabetes, as well as the impact of population aging must be considered.
S-23-4: EFFECTS OF ROTATING NIGHT SHFT ON CIRCADIAN PATTERN OF AMBULATORY BLOOD PRESSURE/HEART RATE, SALIVARY CORTISOL AND SULFATOXY MELATONIN LEVELS
Authors: Anjum B , Verma Narsingh , Tiwari Sandeep , Naz Qulsoom , Singh Ranjana , Mahdi Abbas Ali
Published: January 2023

Objective:

The present study was aimed to investigate effect of Light exposute at night on 24 hours chronomics of BP/HR in terms of Double amplitude, Acrophase and Hyperbaric index and its relation with circadian rhythm of salivary cortisol and 6 sulfatoxy melatonin in rotating night shift nursing professionals and actual day workers.

Design & Methods:

56 night shift nurses, aged 20 to 40 years, performing day and night shift duties were recruited from the Trauma Center, KGMU, India, and 56 age sex matched actual day workers were also enrolled as controls. BP and HR were recorded by Ambulatory Blood Pressure Monitoring (ABPM) at every 30 min intervals in day time and each hour in night time during shift duties.

Results:

Highly significant difference was found in double amplitude (2DA) of among between night (23.10 ± 14.68) and day shift (34.27 ± 16.44) (p < 0.0005). In night shift, hyperbaric index (HBI) of mean SBP was found to be increased at 00 to 03 am (midnight) while during day shift, peak was found at 06 to 09 am. HBI of mean HR was found to be increased at 18 to 21 pm during night shift while in controls, peak was found at 09 to 12 & again 15 to 18 pm of SBP, DBP & HR. Alterations in Acrophase of BP/HR were very common among night shift workers and Ecphasia was found in few nights shift workers. Difference was found in night cortisol levels among night (4.08 ± 3.28) vs day shift (2.62 ± 2.37), while in comparison to night shift or day shift with controls (1.82 ± 1.18) these difference was significant (p < 0.05).

Conclusion:

Alteration in mean morning melatonin and Increased Night cortisol level were found during night shift. Reverse pattern of Acrophase and HBI of BP & HR along with salivary cortisol during night shift represents desynchronization. It indicates that the circadian rhythm was disrupted during night shift and recovery occurs during day shit.
S-24-1: OLD HABITS DIE HARD. REDUCED-SODIUM SCHOOL LUNCHES IN ELEMENTARY SCHOOLS WILL CREATE A NEW LOW-SODIUM EATING HABIT IN JAPAN
Authors: Kusaka Miho
Published: January 2023

To prevent future cerebrovascular disorders, the most important lifestyle improvement measure for Japanese people, who have a high prevalence of hypertension and especially high salt intake, is to reduce salt intake by less than 6 g/day, but progress is slow. If this trend continues, medical and nursing care costs are expected to increase further in the future.

However, it is frustrating to verbally instruct patients who have already developed the habit of eating a high-salt diet on how to reduce salt intake, and younger people, who are less health-conscious, are less interested in salt reduction.

Therefore, it is desirable to create a society in which people can reduce salt intake naturally living a normal life. As a first step toward this goal, we need to promote a low-sodium dietary education for children and low-sodium school lunches at elementary schools. This is because high-salt eating habits do not begin in adulthood, but rather are the accumulation of eating habits from childhood, and we think that acquiring the basics of healthy eating habits as a child will be a major prevention of lifestyle-related diseases, including hypertension, throughout life.

In 2012, a group led by the Japanese Society of Hypertension held the “Salt Reduction Summit in Kure 2012’’, combining research with a salt reduction experience event for the public. One of the goals of the summit was to educate on the importance of salt reduction to children through a program involving children, teachers, government officials, and chefs. This led to the start of reduced-sodium school lunches in elementary schools in Kure City.

Initially, the amount of salt per school lunch was 3.1 g, but this was reduced to 2.0 g by 2021. The salt content was gradually reduced every year, so the goal was achieved without any discomfort and there were no leftover meals. With the introduction of low salt school lunches and providing education on salt reduction by school nutrition teachers, children and their parents’ generation are becoming more interested in salt reduction. The Japanese Society of Hypertension also holds various events for children. If reduced-sodium school lunch programs spread not only through Japan but also around the world, by the time children become adults, the public's preference will be for low-sodium foods, and food companies will appreciate benefits of selling low-sodium products and thereby creating a low-sodium society. As a result, we hope that healthy life expectancy will increase.