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The cardiotoxicity associated with des -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT 2B ) has solidified the receptor's place as an "antitarget" in drug discovery. Conversely, a growing body of evidence has highlighted the utility of 5-HT 2B antagonists for the treatment of pulmonary arterial hypertension (PAH), valvular heart disease (VHD), and related cardiopathies. In this Perspective, we summarize the link between the clinical failure of fenfluramine-phentermine (fen-phen) and the subsequent research on the role of 5-HT 2B in disease progression, as well as the development of drug-like and receptor subtype-selective 5-HT 2B antagonists. Such agents represent a promising class for the treatment of PAH and VHD, but their utility has been historically understudied due to the clinical disasters associated with 5-HT 2B . Herein, it is our aim to examine the current state of 5-HT 2B drug discovery, with an emphasis on the receptor's role in the central nervous system (CNS) versus the periphery.

Kir6.2/SUR1 is an ATP-regulated potassium channel that acts as an intracellular metabolic sensor, controlling insulin and appetite-stimulatory neuropeptides secretion. In this Letter, we present the SAR around a novel Kir6.2/SUR1 channel opener scaffold derived from an HTS screening campaign. New series of compounds with tractable SAR trends and favorable potencies are reported., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The literature demonstrates an association between aspects of caregiving and support with caregiver burden and differences by race. Our objective was to examine correlates of caregiver wellbeing, and if the effect is moderated by race., Methods: The National Study of Caregiving (NSOC) is a survey of unpaid and familial caregivers affiliated with participants in the National Health and Aging Trends Study, a nationally representative survey of Medicare beneficiaries. A total of 899 participants were examined cross-sectionally with logistic and multinomial logistic regression models to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI) for NSOC Round 3 (2017), stratified by race, to determine the association between aspects of caregiving and support variables with the two outcomes, three-level caregiving gains, and response to the statement "life has meaning and purpose.", Results: Among black caregivers with no family or friends to help, there were lower gains compared to very high gains (aOR: 2.82, 95% CI: 1.18, 6.77). Black and white caregivers who endorsed lower ratings regarding being appreciated by the care recipient had lower gains for "life has meaning and purpose" (aOR: 2.46, 95% CI: 1.00, 6.02; aOR: 1.65, 95% CI: 1.06, 2.56). Black caregivers with lower ratings regarding being appreciated had lower gains compared to very high gains (aOR: 5.04, 95% CI: 1.48, 17.17). White caregivers endorsing lower ratings to the same question had lower gains compared to very high gains (aOR: 3.27, 95% CI: 1.77, 6.04), and those with more help had lower gains (aOR: 0.81, 95% CI: 0.70, 0.93)., Conclusion: The relationship between various correlates and positive aspects of caregiving is moderated by black and white races. Further study on the impact of aspects of caregiving and support networks for caregivers may shed light on factors contributing to racial differences and areas for intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Parr and Mielenz.)