Catheter-based adrenal ablation: an alternative therapy for patients with aldosterone-producing adenoma.

Unilateral adrenalectomy is the standard treatment for patients with aldosterone-producing adenoma (APA), but it lacks an option for patients with APA who refuse or are not suitable for surgery. In this study, we studied whether catheter-based adrenal ablation for APA is comparable to adrenalectomy. A total of 2185 hypertensive patients were screened, and 112 patients with APA were recruited and counselled on the treatment options. Fifty-two patients opted for catheter-based adrenal ablation, and 60 opted for adrenalectomy. Clinical and biochemical outcomes were assessed at 6 months after treatment. Factors associated with hypertension remission and the advantages and limitations of this approach were evaluated. According to the primary aldosteronism surgical outcome (PASO) criteria, complete and partial clinical success was achieved in 21 (40.4%) and 23 (44.2%) patients in the ablation group vs. 33 (55.0%) and 23 (38.3%) patients in the adrenalectomy group, respectively. Complete and partial biochemical success was achieved in 30 (57.7%) and 17 (32.7%) patients in the ablation group vs. 51 (85.0%) and 5 (8.3%) patients in the adrenalectomy group, respectively. The complete clinical success rate was not (P > 0.05), but the complete biochemical success rate was significantly different between the two groups (P < 0.01). Factors associated with adrenal ablation-mediated hypertension remission were hypertension duration and serum potassium level at baseline. Compared with surgery, adrenal ablation requires a shorter operating time and time to resume physical activity. Catheter-based adrenal ablation may be an alternative and feasible option for APA patients unwilling to receive surgical treatment.

Analysis of Social Mission Commitment at Dental, Medical, and Nursing Schools in the US.

Importance: The COVID-19 pandemic and calls for racial justice have highlighted the need for schools to promote social mission. Measuring social mission engagement and performance in health professions education may encourage institutional efforts to advance health equity and social justice commitments. Objective: To describe the current state of social mission commitment within dental, medical, and nursing schools in the US and to examine how social mission performance compares across school types. Design, Setting, and Participants: This cross-sectional survey study invited all US dental and medical schools and a subset of baccalaureate- and master's degree-conferring nursing schools to participate in a self-assessment to measure their school's social mission commitment from January 29 through October 9, 2019. The survey measured 79 indicators (with indicators defined as responses to specific scored questions that indicated the state or level of social mission commitment) across 18 areas in 6 domains of school functioning (educational program, community engagement, governance, diversity and inclusion, institutional culture and climate, and research) that have potential to enhance social mission engagement and performance. Individual health professions schools were the unit of analysis, and 689 dental, medical, and nursing schools were invited to participate. School deans and program directors were the primary target respondents because of their broad insight into their school's programs and policies and their ability to request data from various internal sources. Demographic information from respondents was not collected because multiple respondents from an institution could complete different sections of the survey. Main Outcomes and Measures: Survey responses were analyzed to create indicator scores, standardized area scores, and an overall social mission score for each school. Using descriptive analyses, frequency and contingency tables of specific indicators within each area were created, and schools were compared based on ownership status (private or public), Carnegie Classification of Institutions of Higher Education research classification group (doctoral university with very high research activity [R1], doctoral university with high [R2] or moderate [R3] research activity, baccalaureate or master's nursing college or university, or special focus institution), and discipline group (dental school, medical school granting doctor of osteopathic medicine [DO] degrees, medical school granting doctor of medicine [MD] degrees, nursing school granting baccalaureate-level degrees, or nursing school granting master's-level degrees). Results: Among 689 invited schools, 242 schools (35.1%) completed the self-assessment survey. Of those, 133 (55.0%) were nursing schools, 83 (34.3%) were medical schools, and 26 (10.7%) were dental schools. Response rates ranged from 133 of 420 invited nursing schools (31.7%) to 83 of 203 invited medical schools (40.9%). Most schools included social determinants of health in their curriculum in either required courses (233 of 242 schools [96.3%]) or elective courses (4 of 242 schools [1.7%]), but only 116 of 235 schools (49.4%) integrated social determinants of health across all years of study. Most schools also included health disparities in either their required courses (232 of 242 [95.9%]) or elective courses (6 of 242 [2.5%]); however, only 118 of 235 schools (50.2%) integrated health disparities across all years of study. In several areas of social mission, public schools performed better than private schools (eg, curriculum: mean [SE] standardized area score, 0.13 [0.07] points vs -0.14 [0.09] points, respectively), and R1 doctoral universities and special focus institutions performed better than R2 and R3 doctoral universities and baccalaureate and master's nursing colleges and universities (eg, extracurricular activities: mean [SE] standardized area score, 0.25 [0.09] points for R1 doctoral universities and 0.20 [0.12] points for special focus institutions vs -0.05 [0.12] points for R2 and R3 doctoral universities and - 0.30 [0.12] points for baccalaureate and master's nursing colleges and universities. Different areas of strength emerged for dental, medical, and nursing schools. For example, in the curriculum area, MD-granting medical schools had a mean (SE) standardized area score of 0.38 (0.08) points, which was significantly higher than the standardized area scores of dental schools (mean [SE], -0.21 [0.14] points), DO-granting medical schools (mean [SE], -0.22 [0.13] points), graduate nursing schools (mean [SE], -0.21 [0.19] points), and undergraduate nursing schools (mean [SE], -0.05 [0.10] points). Conclusions and Relevance: In this study, there was widespread interest from health professions educational leaders in understanding and enhancing social mission commitment. Future work may focus on identifying and promoting best practices using the framework described, providing schools with continued opportunities for self-assessment, and further validating the self-assessment survey.

Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction.

High salt intake is a known risk factor of cardiovascular diseases. Our recent study demonstrated that long-term high salt intake impairs transient receptor potential channel M5 (TRPM5)-mediated aversion to high salt concentrations, consequently promoting high salt intake and hypertension; however, it remains unknown whether TRPM5 activation ameliorates cardiovascular dysfunction. Herein we found that bitter melon extract (BME) and cucurbitacin E (CuE), a major compound in BME, lowered high salt-induced hypertension. Long-term BME intake significantly enhanced the aversion to high salt concentrations by upregulating TRPM5 expression and function, eventually decreasing excessive salt consumption in mice. Moreover, dietary BME ameliorated high salt-induced cardiovascular dysfunction and angiotensin II-induced hypertension in vivo. The mechanistic evidence demonstrated that dietary BME inhibited high salt-induced RhoA/Rho kinase pathway overactivation, leading to reduced phosphorylation levels of myosin light chain kinase and myosin phosphatase targeting subunit 1. Furthermore, CuE inhibited vasoconstriction by attenuating L-type Ca2+ channel-induced Ca2+ influx in vascular smooth muscle cells. To summarize, our findings indicate that dietary BME has a beneficial role in antagonizing excessive salt consumption and thus appears promising for the prevention of high salt-induced cardiovascular dysfunction.

Activation of Transient Receptor Potential Melastatin Subtype 8 Attenuates Cold-Induced Hypertension Through Ameliorating Vascular Mitochondrial Dysfunction.

BACKGROUND: Environmental cold-induced hypertension is common, but how to treat cold-induced hypertension remains an obstacle. Transient receptor potential melastatin subtype 8 (TRPM8) is a mild cold-sensing nonselective cation channel that is activated by menthol. Little is known about the effect of TRPM8 activation by menthol on mitochondrial Ca2+ homeostasis and the vascular function in cold-induced hypertension. METHODS AND RESULTS: Primary vascular smooth muscle cells from wild-type or Trpm8-/- mice were cultured. In vitro, we confirmed that sarcoplasmic reticulum-resident TRPM8 participated in the regulation of cellular and mitochondrial Ca2+ homeostasis in the vascular smooth muscle cells. TRPM8 activation by menthol antagonized angiotensin II induced mitochondrial respiratory dysfunction and excess reactive oxygen species generation by preserving pyruvate dehydrogenase activity, which hindered reactive oxygen species-triggered Ca2+ influx and the activation of RhoA/Rho kinase pathway. In vivo, long-term noxious cold stimulation dramatically increased vasoconstriction and blood pressure. The activation of TRPM8 by dietary menthol inhibited vascular reactive oxygen species generation, vasoconstriction, and lowered blood pressure through attenuating excessive mitochondrial reactive oxygen species mediated the activation of RhoA/Rho kinase in a TRPM8-dependent manner. These effects of menthol were further validated in angiotensin II-induced hypertensive mice. CONCLUSIONS: Long-term dietary menthol treatment targeting and preserving mitochondrial function may represent a nonpharmaceutical measure for environmental noxious cold-induced hypertension.

Activation of TRPV4 by dietary apigenin antagonizes renal fibrosis in deoxycorticosterone acetate (DOCA)-salt-induced hypertension.

Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remains elusive. In the present study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks. Apigenin significantly attenuated the DOCA-salt-induced structural and functional damage to the kidney, which was accompanied by reduced expression of transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signaling pathway and extracellular matrix proteins. Immunochemistry, cell-attached patch clamp and fluorescent Ca2+ imaging results indicated that TRPV4 was expressed and activated by apigenin in both the kidney and renal cells. Importantly, knockout of TRPV4 in mice abolished the beneficial effects of apigenin that were observed in the DOCA-salt hypertensive rats. Additionally, apigenin directly inhibited activation of the TGF-ß1/Smad2/3 signaling pathway in different renal tissues through activation of TRPV4 regardless of the type of pro-fibrotic stimulus. Moreover, the TRPV4-mediated intracellular Ca2+ influx activated the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway, which inhibited the TGF-ß1/Smad2/3 signaling pathway. In summary, dietary apigenin has beneficial effects on hypertension-induced renal fibrosis through the TRPV4-mediated activation of AMPK/SIRT1 and inhibition of the TGF-ß1/Smad2/3 signaling pathway. This work suggests that dietary apigenin may represent a promising lifestyle modification for the prevention of hypertension-induced renal damage in populations that consume a high-sodium diet.