Evaluating and Comparing the Correlation and Performance of PROMIS and FAAM ADL in a Foot and Ankle Patient Population.

BACKGROUND: There is a paucity of literature assessing 2 of the commonly used static Patient-Reported Outcomes Measurement Information System (PROMIS) forms (PROMIS Global-10 and PROMIS Physical Function Short Form 10a [PF SF 10a]) and the Foot and Ankle Ability Measure Activities of Daily Living (FAAM ADL). METHODS: The PROMIS Global-10, PROMIS PF SF 10a, and FAAM ADL were compared among new foot and ankle patients. Spearman rho (ρ) correlations were calculated, and ceiling and floor effects were determined. RESULTS: The FAAM ADL demonstrated strong correlations with PROMIS PF SF 10a, P = .88, 95% confidence interval (CI): 0.86-0.90, P < .001, and PROMIS Global-10 Physical Health (P = .75, 95% CI: 0.71-0.78, p < .001). The FAAM ADL and PROMIS Global-10 Mental Health demonstrated a moderate correlation (P = .41, 95% CI: 0.34-0.47, P < .001). No PROM demonstrated an appreciable floor effect. The PROMIS Global-10 Physical Health demonstrated the lowest ceiling effect (n=11 [1.6%]). CONCLUSION: Because the PROMIS Global-10 captures physical health adequately, provides mental health insight, and performs as well (if not better), we recommend the PROMIS Global-10 among the PROMs studied.Level of Evidence: Level III.

Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products.

The serotonin 5-HT2 receptors are important pharmaceutical targets involved in signaling pathways underlying various neurological, psychiatric, and cardiac functions and dysfunctions. As such, numerous ligands for the investigation of these receptors' activity and downstream effects have been developed synthetically or discovered in nature. For example, the heteroyohimbine natural product alstonine exhibits antispychotic activity mediated by 5-HT2A/2C agonism. In this work, we identified a heteroyohimbine metabolite containing a serotonin pharmacophore and truncated the scaffold, leading to the discovery of potent agonist activity of substituted tetrahydro-ß-carbolines across the 5-HT2 receptor family. Extensive SAR development resulted in compound 106 with EC50 values of 1.7, 0.58, and 0.50 nM at 5-HT2A, 5-HT2B, and 5-HT2C, respectively. Docking studies suggest a π-stacking interaction between the tetrahydro-ß-carboline core and conserved residue Trp6.48 as the structural basis for this activity. This work lays a foundation for future investigation of these compounds in neurological and psychiatric disorders.