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BACKGROUND The rehospitalization rate in a hypertensive emergency is high, indicating the necessity for optimizing its long-term management. The role of the renin–angiotensin system (RAS) blockade in this disorder remains uncertain. METHODS We conducted a retrospective analysis involving 20 admitted patients who received aliskiren, a direct renin inhibitor (DRI), for the management of hypertensive emergency associated with elevated plasma renin activity (PRA). We analyzed the changes in blood pressure (BP), kidney function, and RAS activity in the subacute and chronic phases. RESULTS The use of DRI was associated with a marked reduction in PRA (median, from 25.0 to 1.2 ng/ml/h) and serum aldosterone levels (from 404 to 130 pg/ml) during the index admission. BP also decreased from 226/143 to 142/80 mm Hg. A comparison of clinical characteristics according to the renal function indicated that dialysis-dependent patients had higher aldosterone levels than non-dialysis-dependent patients at admission, despite comparable BP levels. After a median follow-up of 567 days in non-dialysis-dependent patients with DRI, eGFR levels were significantly increased from 14.3 to 23.1 ml/min/1.73 m2. PRA levels were consistently suppressed at 0.8 ng/ml/h. We found a significant correlation between the degree of PRA suppression and changes in eGFR (r  = –0.58), indicating that the effective blockade of RAS is associated with the preservation of eGFR in the study subjects. CONCLUSIONS DRI can successfully suppress PRA in patients with high-renin hypertensive emergency in both subacute and chronic phases. An efficient RAS blockade is associated with preserved renal function in these patients. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a severe life-threatening hypersensitivity reaction induced by mast cell degranulation. Among the various mediators of mast cells, little is known about the role of tryptase. Therefore, we aimed to elucidate the role of protease-activating receptor-2 (PAR-2), a receptor activated by tryptase, in murine anaphylactic models using PAR-2-deficient mice and newly generated tryptase-deficient mice. Anaphylaxis was induced by IgE-dependent and IgE-independent mast cell degranulation in mice. PAR-2 deficiency exacerbated the decrease in body temperature and hypotension during anaphylaxis; however, the number of skin mast cells, degree of mast cell degranulation, and systemic and local vascular hyperpermeability were comparable in PAR-2 knockout and wild-type mice. Nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), is an indispensable vasodilator in anaphylaxis. In the lungs of anaphylactic mice, PAR-2 deficiency promoted eNOS expression and phosphorylation, suggesting a protective effect of PAR-2 against anaphylaxis by downregulating eNOS activation and expression. Based on the hypothesis that the ligand for PAR-2 in anaphylaxis is mast cell tryptase, tryptase-deficient mice were generated using CRISPR-Cas9. In wild-type mice, the PAR-2 antagonist exacerbated the body temperature drop due to anaphylaxis; however, the effect of the PAR-2 antagonist was abolished in tryptase-deficient mice. These results suggest that tryptase is a possible ligand of PAR-2 in anaphylaxis and that the tryptase/PAR-2 pathway attenuates the anaphylactic response in mice. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is an infectious disease caused by parasitic protozoa of the genus Leishmania and manifests clinical symptoms such as splenomegaly, hepatomegaly, anemia, and fever. It has previously been shown that B-cell-activating factor (BAFF) is involved in splenomegaly during VL. Although BAFF is known to be expressed by a variety of cells, the mechanism of elevated BAFF expression in VL is not clear. In this study, we aimed to identify BAFF-producing cells in the spleens of mice infected with Leishmania donovani. Splenocytes of L. donovani-infected mice showed elevated BAFF expression compared to that of naive mice. In the infected spleen, the number of both CD11b+ and F4/80+ cells increased, and the major BAFF-producing cells were CD11b+ cells, which did not serve as host cells of Leishmania. Immunohistochemical/immunofluorescent staining of spleens of infected mice revealed that the increased CD11b+ cells were primarily MRP14+ mononuclear cells. Together, these results suggest the increased BAFF expression in the spleen of L. donovani-infected mice involves a recruitment of inflammatory macrophages distinct from host macrophages for the parasites. [ABSTRACT FROM AUTHOR]

Introduction: Since the needs for dental care among older adults in Japan are expected to increase in the future, this study aimed to examine the influence of ageism among dental students and clinical trainees on the attitude towards the older adults in dental care. Materials and Methods: In 2022, we conducted a questionnaire survey of 9th‐, 11th‐semester dental students and first‐year clinical trainees enrolled at Kyushu Dental University, using the Japanese version of Ageism Scale for Dental Students (ASDS‐J), Japanese version of Fraboni Scale of Ageism (FSA‐J). Questions on intention to provide dental care to the older adults, relationships with the older adults and living with the older adults were also surveyed. Results: There were 162 participants (84 males and 78 females), and the response rate was 71.7%. The participants were divided into the positive group for dental care to older adults (68 respondents) and the negative group (94 respondents). The ASDS‐J score of the negative group was significantly higher than that of the positive group [49 (36–66) vs. 52 (34–88), p <.001]. The binomial logistic regression analysis revealed that the odds ratio of being negative attitude was 1.1 per one point of ASDS‐J (95% confidence interval: 1.0–1.2) in the model adjusted for student grade, interaction with the older adults, gender, experience living with the older adults and FSA‐J. Conclusion: These findings suggest that ageism specific to dental students and clinical trainees (as assessed using the ASDS‐J) was independently correlated with negative attitudes towards dental care for older adults. [ABSTRACT FROM AUTHOR]

Background: Clarifying how tongue pressure in convalescent stroke patients affects oral condition and activities of daily living (ADL) is important for developing oral rehabilitation programs and for rehabilitation care to reacquire ADL. Objective: To clarify how tongue pressure is associated with oral status, ADL, and nutritional status in stroke patients. Methods: Sixty‐eight patients aged 77.9 ± 10.0 years participated. The Japanese version of the Oral Health Assessment Tool was used to evaluate oral status. Data such as the ADL index functional independence measure (FIM), nutritional intake method, serum albumin, and body mass index were extracted from medical records. To examine factors associated with tongue pressure, multiple regression analysis was performed adjusting for confounding factors. The level of statistical significance was set at p <.05. Results: In recovery phase stroke patients, tongue pressure was significantly lower in the total assistance group than in the partial assistance/independent group. In addition, tongue pressure was significantly lower in tube feeding patients than in oral feeding patients. FIM cognition score was an independent factor that had a significant effect on tongue pressure. Conclusion: These findings suggest that ADL status also affects tongue pressure, thus patients' ADL including the FIM cognition subscale should also be evaluated while measuring tongue pressure. [ABSTRACT FROM AUTHOR]

Aim: Tongue strength plays an important role in the process of food intake, and low tongue pressure has been associated with aspiration pneumonia, cognitive decline, and mortality. However, special equipment for tongue pressure measurement is uncommon in general practice. Recently, the serum creatinine‐to‐cystatin C (Cr/CysC) ratio has been validated as a marker of muscle volume mass. Thus, we aimed to investigate the association of the serum Cr/CysC ratio with tongue pressure in a cross‐sectional study. Methods: This single‐center, cross‐sectional study enrolled 73 participants (mean age, 71.7 years; men, 49.3%) who regularly attended the hospital for treatment of chronic disease. A tongue pressure of <30 kPa was defined as low tongue pressure. We evaluated the relationships between the serum Cr/CysC ratio and tongue pressure using multiple regression analysis. Results: The serum Cr/CysC ratio was correlated with tongue pressure (R2 = 0.25, P < 0.0001). In multiple regression analyses adjusted for confounders including age, sex, body mass index, and serum albumin, the association remained significant (P = 0.0001). In logistic analyses, the multivariable‐adjusted odds ratios of the Cr/CysC ratio for tertiles 1 and 2 compared with tertile 3 for low tongue pressure were 7.81 (95% confidence interval, 1.45–51.73) and 2.71 (95% confidence interval, 0.60–13.19), respectively. Conclusions: We demonstrated that a decreased serum Cr/CysC ratio was associated with a higher risk of low tongue pressure. Our findings suggest that this simple serum surrogate marker may be a first step toward an intervention for oral function by general practitioners. Geriatr Gerontol Int 2024; 24: 102–108. [ABSTRACT FROM AUTHOR]

Chondrogenesis is strictly regulated by several factors, including cytokines, hormones, and extracellular matrix proteins. Mouse teratocarcinoma‐derived lineage cells, differentiate into chondrocytes in the presence of insulin. Although ascorbic acid promotes chondrogenic differentiation, the detailed regulative mechanisms underlying its role in chondrogenesis remain unclear. Therefore, in this study, we evaluated the effects of ascorbic acid on insulin‐induced chondrogenic differentiation of ATDC5 cells and the underlying intracellular signaling. The results revealed that insulin‐stimulated collagen deposition, matrix formation, calcification, and expression of chondrogenic differentiation marker genes in ATDC5 cells. This enhancement by insulin was amplified with the addition of ascorbic acid. Molecular analysis revealed that the activation of insulin‐induced phosphoinositide 3‐kinase (PI3K)/Akt signaling was enhanced in the presence of ascorbic acid. In contrast, Wnt/β‐catenin signaling was suppressed during chondrocyte differentiation via upregulation of the Wnt agonist, secreted Frizzled‐related protein 1 (sFRP‐1) and 3 (sFRP‐3). Notably, ascorbic acid upregulated the expression of insulin receptors and their substrates (IRS‐1 and IRS‐2). Furthermore, ascorbic acid reversed the suppression of IRS‐1 and IRS‐2 protein by insulin. These results indicate that ascorbic acid positively regulates the chondrogenic differentiation of ATDC5 cells via enhancement of insulin signaling. Our findings provide a substantial basis for further elucidation of the regulatory mechanisms of chondrocyte differentiation and the pathophysiology of OA, thus aiding in development of effective treatment strategies. [ABSTRACT FROM AUTHOR]

Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific [CD8.sup.+] T cell accumulation in infection sites by downregulating expression of the [CD8.sup.+] T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis. Direct injection of CXCL9 into the CNS infection site enhanced HSV-1-specific [CD8.sup.+] T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of [CD8.sup.+] T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis., Introduction HSV-1 is generally associated with various mucocutaneous diseases, such as herpes labialis, genital herpes, herpetic whitlow, and keratitis (1). Also, HSV-1 is the most common cause of sporadic viral [...]