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Abstract Background Hypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies. Methods We enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed. Results Among 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman’s coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]). Conclusion In patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient.

Abstract Background Although transcatheter aortic valve implantation (TAVI) is assumed to be a less invasive therapy in high-risk patients with aortic valve stenosis (AS), there have been limited data suggesting its beneficial effects on cardiovascular mortality in Japanese patients receiving dialysis therapy. Methods Hemodialysis patients with severe AS underwent either TAVI (n = 33) or surgical aortic valve replacement (SAVR, n = 25). We compared the postoperative outcomes and perioperative complications, including dialysis-associated parameters [e.g., intradialytic hypotension (IDH)], between TAVI and SAVR. Results A 30-day and 1-year mortality rate was nearly the same among the TAVI and the SAVR group. Incidence of permanent pacemaker implantation or other events, including stroke, bleeding and vascular complications, in the TAVI group were not different from those in SAVR patients during the 30-day or 1-year postoperative period. The incidence of IDH was increased following SAVR (odds ratio (OR) = 11.29 [95% CI 1.29–98.89]) but was not affected by TAVI (OR = 1.55 [95% CI 0.24–9.94]). Among the patients aged 75 or older, the incidence of IDH was particularly conspicuous in the SAVR group (OR = 15.75 [95% CI 2.30–107.93]). Because there were differences in background data (age, EuroSCORE II, and dialysis duration) between these groups, propensity score-matched analysis was conducted and showed no difference in the composite event-free probability between the TAVI and the SAVR group over one year (p = 0.816). Conclusions TAVI offers an alternative strategy to Japanese hemodialysis patients with severe AS, with nearly the same incidence of complications as SAVR during 1-year observation.

ABSTRACT Aims/Introduction Linagliptin is a selective dipeptidyl peptidase (DPP)‐4 inhibitor capable of successfully regulating blood glucose levels. The cardiovascular protective effects of several DPP‐4 inhibitors have been shown in preclinical studies; however, the detailed influence of DPP‐4 inhibitors on diabetic pathological alterations in cardiac tissue has not yet been elucidated. Materials and Methods We combined laboratory‐based experiments and bioinformatics techniques to identify suitable candidate targets with significant biological pathways. Mice with streptozotocin‐induced insulin deficiency diabetic model were utilized for in vivo experiments. Mice were euthanized at 24 weeks after the induction of diabetes; linagliptin intervention was carried out for 4 weeks before euthanasia. Microarray analysis of heart samples was carried out. Results Mice with streptozotocin‐induced diabetes, but not control mice, showed cardiac fibrosis with an endothelial–mesenchymal transition program, and myocardial fiber and sarcomere disruption; linagliptin alleviated these diabetes‐associated pathological alterations without altering blood glucose levels. Bioinformatics analysis utilizing a microarray dataset identified 10 hub genes that were confirmed to have human disease relevance by Gene Expression Omnibus analysis. Among these hub genes, we focused on the Sox9–necroptosis axis as a therapeutic target in diabetic hearts. Indeed, diabetic mice showed the induction of necroptosis‐associated genes and the phosphorylation of RIP3 and mixed lineage kinase domain‐like protein. Conclusions Linagliptin showed excellent heart protection in mice with streptozotocin‐induced diabetes associated with alterations in human disease‐relevant hub genes. Further investigation is required to determine why DPP‐4 inhibitors do not show similar superior organ‐protective effects in the clinical setting.

This study aims to explore the current “double ageing” (demographic ageing of residents and physical ageing of facilities) in high-rise (over 20 stories by the Japanese Government’s definition) residential buildings in Tokyo, where the rate of ageing has increased most rapidly since the late 1990s, compared to those of other cities and high-rise residential buildings worldwide. First, the trend of demographic ageing in the districts where high-rise residential buildings are concentrated is analysed. The results show that demographic ageing in high-rise residential buildings is faster than in other residential buildings because the age group of the residents is concentrated across two generations: the generation born in 1946–1955 and the generation born in 1966–75. Second, the relationship between demographic and physical ageing was examined through an online survey of 978 residents of high-rise residential buildings conducted in January 2021. A generation gap in values regarding their high-rise residential buildings was clearly identified. Third, the cause and result of the generation concentration and gap were investigated via an interview survey of 26 informants extracted from the online survey. Three main findings emerged: (a) the ageing of the generation born in 1946–1955 has given rise to housing insecurity because of the decline in income, (b) the high rate of singles within the generation born in 1966–1975 may be as a result of housing insecurity after their retirement, and (c) the introduction of social distancing has accelerated the substantial “ageing” of relatively good facilities, but a straightforward generational conflict was not fully deciphered in this article because of lifestyle diversification over generations and organisational culture of management associations.

Abstract Aims/Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been shown to display excellent renoprotective effects in diabetic kidney disease with macroalbuminuria/proteinuria. Regarding the renoprotective mechanism of SGLT2i, a sophisticated hypothesis was made by explaining the suppression of glomerular hypertension/hyperfiltration through the adenosine/adenosine type 1 receptor (A1R) signaling‐mediated restoration of the tubuloglomerular feedback mechanism; however, how such A1R signaling is relevant for renoprotection by SGLT2i in diabetic kidney disease with proteinuria has not been elucidated. Materials and Methods Streptozotocin‐induced diabetic CD‐1 mice were injected with bovine serum albumin (BSA) and treated with SGLT2i in the presence/absence of A1R inhibitor administration. Results We found that the influences of SGLT2i are essentially independent of the activation of A1R signaling in the kidney of BSA‐overloaded streptozotocin‐induced diabetic mice. BSA‐overloaded diabetic mice showed the trend of kidney damage with higher glomerular filtration rate (GFR) and the significant induction of fibrogenic genes, such as transforming growth factor‐β2 and collagen type III. SGLT2i TA‐1887 suppressed diabetes‐induced GFR in BSA‐overloaded diabetic mice was associated with the significant suppression of transforming growth factor‐β2 and collagen type III; A1R‐specific inhibitor 8‐cyclopentyl‐1,3‐dipropylxanthine did not cancel the effects of TA‐1887 on either GFR or associated gene levels. Both TA‐1887 and 8‐cyclopentyl‐1,3‐dipropylxanthine‐treated BSA‐overloaded diabetic mice showed suppressed glycated hemoglobin levels associated with the increased food intake. When analyzing the association among histological evaluation, GFR and potential fibrogenic gene levels, each group of mice showed distinct correlation patterns. Conclusions A1R signaling activation was not the dominant mechanism on the influence of SGLT2i in the kidney of BSA‐overloaded diabetic mice.

Abstract Aims/Introduction The aim of this study was to elucidate whether sodium–glucose cotransporter 2 inhibitors (SGLT2is) treatment has any renoprotective effect for type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) of

Abstract A 58‐year‐old women who was diagnosed with type 2 diabetes 20 years earlier had been treated with antidiabetic medicines since she was aged 40 years. After sodium–glucose cotransporter 2 inhibitors administration, her bodyweight rapidly decreased from 40 to 30 kg over a period of 3 weeks. She had abdominal symptoms, including nausea, especially after a meal. On admission, physical examinations and laboratory data showed euglycemic ketoacidosis, dehydration and low insulin secretion levels. Additionally, abdominal contrast computed tomography showed the finding of superior mesenteric artery syndrome. This case urges caution, including rapid excessive bodyweight loss and euglycemic ketoacidosis, on the use of sodium–glucose cotransporter 2 for lean diabetes patients.

In this paper, based on my research about the mutual aids between local governments after the Great East Japan Disaster (3.11), I try to describe the process in which I have collected data based on typical theories and through the interaction with informants belonging to local governments in order to discuss the possible relationship between data and theories. First of all, I evaluate two recent empirical studies both of which reached one similar conclusion on one of the typical theoretical perspective shared by most researchers on Japanese society after 3.11. I name this perspective "divergent theory" because that perspective should generally point out the divergence of two incompatible forms of norm or narratives on political responses to that disaster. Secondly, I describe the data-producing process in which I have collected the data about the decision-making of mutual aid implementation initially through structured questionnaires which were planned based on those static theories and then I modified these data through face-toface interviews. Consequently, I have come to interpret these political responses to disaster as convergence rather than divergence referring not only to my own process-produced data but to Luhmann's sociological theory which was produced by comparative observation of interactions within political processes. Finally, I describe reactions of my informants who were introduced to my theoretical interpretation as part of the open-ended process of a reflexive relationship between data and theories in my research, which should be called "action research." [ABSTRACT FROM AUTHOR]