Neurokinin receptor antagonists as potential non-hormonal treatments for vasomotor symptoms of menopause.

Vasomotor symptoms of menopause (VMS), otherwise known as hot flashes, can significantly impact women's quality of life. Up to 87% of women report hot flashes during or after their menopause transition, and can last for a median duration of 7.4 years. The current mainstay of treatment and the most effective treatment for VMS is hormone therapy with estrogen. However, hormone therapy is not without risk, and the discovery of an effective nonhormonal treatment option with neurokinin B receptor antagonists for VMS provides an encouraging and potentially practice-changing treatment option for all women. This review will discuss the pathophysiology and mechanism of action, as well as review the current compounds in development targeting the neurokinin receptors.

Biocatalytic Intramolecular C-H aminations via Engineered Heme Proteins: Full Reaction Pathways and Axial Ligand Effects.

Engineered heme protein biocatalysts provide an efficient and sustainable approach to develop amine-containing compounds through C-H amination. A quantum chemical study to reveal the complete heme catalyzed intramolecular C-H amination pathway and protein axial ligand effect was reported, using reactions of an experimentally used arylsulfonylazide with hemes containing L=none, SH- , MeO- , and MeOH to simulate no axial ligand, negatively charged Cys and Ser ligands, and a neutral ligand for comparison. Nitrene formation was found as the overall rate-determining step (RDS) and the catalyst with Ser ligand has the best reactivity, consistent with experimental reports. Both RDS and non-RDS (nitrene transfer) transition states follow the barrier trend of MeO-

Effect of Unilateral Cordotomy on Perception of Dysphagia.

OBJECTIVES: CO2 laser medial transverse cordotomy is a permanent static procedure performed to achieve adequate functional airway in cases of posterior glottic stenosis and bilateral vocal fold paralysis. Although it is the preferred method to manage long-term bilateral vocal fold immobility, it is widely believed that cordotomy has the potential to cause aspiration. The minimal existing data on the effect surgical enlargement of the glottic airway on swallowing function is heterogeneous. Through investigation of dysphagia after cordotomy, we hope to better understand the influence of glottic function and its role in dysphagia. The Eating Assessment Tool (EAT-10), is a validated dysphagia symptom-specific outcome measure. We hypothesized that EAT-10 scores would not change after CO2 laser cordotomy despite causing glottic insufficiency. METHODS: Retrospective review was performed on sequential patients having undergone unilateral CO2 laser cordotomy with complete pre- and postoperative EAT-10 questionnaire data available for evaluation. RESULTS: Fifteen patients were available for analysis; 10 patients underwent primary unilateral medial transverse cordotomy, 5 patients underwent revision cordotomy, and 20 unique procedures were included in the dataset. The median EAT-10 score during the visit prior to surgery was 3.5, whereas the post-surgery median score was 2. Furthermore, the median difference of 0 was statistically non-significant (P = .91). CONCLUSION: CO2 laser cordotomy does not contribute to patient-reported dysphagia despite creating glottic incompetence. This suggests vocal fold apposition may play a less significant role in normal swallowing function than widely believed.