N-Branched Tricyclic Guanidines as Novel Melanocortin-3 Receptor Agonists and Melanocortin-4 Receptor Antagonists.

The melanocortin receptors are a class of centrally and peripherally expressed G protein-coupled receptors, of which the MC3R and MC4R subtypes are implicated in the regulation of appetite and energy homeostasis and can serve as potential therapeutic targets for disorders such as obesity and cachexia. An unbiased high-throughput mixture-based library screen was implemented to identify novel ligands with an emphasis on the identification of nanomolar-potent agonists of the mouse melanocortin-3 receptor. This screen yielded the discovery of an N-branched tricyclic guanidine scaffold (TPI2408) that contained three nanomolar potent mMC3R agonists and additional compounds that possessed antagonism for the mMC4R.

Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity.

Background: Rare variants in melanocortin 4 receptor gene (MC4R) result in a severe form of early-onset obesity; however, it is unclear how these variants may affect abdominal fat distribution, intrahepatic fat accumulation, and related metabolic sequelae.

Methods: Eight hundred seventy-seven youth (6-21 years) with overweight/obesity, recruited from the Yale Pediatric Obesity Clinic in New Haven, CT, underwent genetic analysis to screen for functionally damaging, rare variants (MAF < 0.01) in MC4R.

Perceived everyday discrimination, socioeconomic status, and mammography behavior.

Black women (BW) experience age-adjusted breast cancer mortality rates that are 40% higher than White women. Although, screening rates for breast cancer are similar between White and Black women, differences in mammography utilization exist among women with lower socioeconomic status (SES). Moreover, perceived everyday discrimination (PED) has been shown to have an inverse relationship on health screening behavior among BW.

Preoperative Immersive Virtual Reality Applied to Percutaneous Nephrolithotomy: A Prospective Randomized Clinical Study of Surgical Planning and Clinical Outcomes.

Purpose: Percutaneous nephrolithotomy (PCNL) is the procedure of choice for the management of complex or large renal stones. A major challenge for the surgeon, however, is the need to assimilate the nearly 2000 static images from a CT scan into a functional mental image to enable surgical planning. Accordingly, we investigated the potential of immersive virtual reality (iVR) to enhance surgical planning and its impact on the outcomes among patients undergoing PCNL.

Separate mechanisms regulating accumbal taurine levels during baseline conditions and following ethanol exposure in the rat.

Ethanol-induced dopamine release in the nucleus accumbens (nAc) is associated with reward and reinforcement, and for ethanol to elevate nAc dopamine levels, a simultaneous increase in endogenous taurine is required within the same brain region. By employing in vivo microdialysis in male Wistar rats combined with pharmacological, chemogenetic and metabolic approaches, our aim with this study was to identify mechanisms underlying ethanol-induced taurine release. Our results demonstrate that the taurine elevation, elicited by either systemic or local ethanol administration, occurs both in presence and absence of action potential firing or NMDA receptor blockade.