Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate delays aging phenotypes in mice.

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period.

Pain Experience and Tolerance of Awake In-Office Upper Airway Procedures: Influencing Factors.

OBJECTIVES/HYPOTHESIS: Awake, unsedated in-office upper airway procedures are performed frequently and have high completion rates, yet less is known about the patients' pain experience and potentially influencing factors. It is also unclear if patients' pain experiences become worse with repeated procedures. We identified procedure- and patient-related factors that might influence procedural completion and pain scores. STUDY DESIGN: Retrospective chart review. METHODS: Pre-, intra-, and post-procedure pain scores were collected prospectively for awake unsedated upper airway procedures performed at a single institution over a 5-year period. Patient factors reviewed were demographics, body mass index, psychiatric and/or pain diagnosis, and related medications. Procedure factors reviewed were procedure type, route, side, and performance of the same procedure multiple times. Patients reported their pain level before, during, and after the procedure using a standard 0 to 10 scale. Maximum pain score change (PΔmax), or the difference between highest and lowest reported pain levels, was calculated. Descriptive and multivariate analyses were performed. RESULTS: Procedure completion was 98.7% for 609 first time patients and 99.0% in 60 patients undergoing 292 repeat procedures. PΔmax did not covary with age, gender, or BMI. PΔmax covaried with pain and psychiatric conditions and associated medications. PΔmax was highest for injection medialization and lowest for tracheoscopy. PΔmax decreased over time for those undergoing multiple identical procedures. CONCLUSIONS: Procedures were performed with a very high completion rate and low pain scores. Age, sex, and BMI did not affect pain experience. A combination of pain and psychiatric conditions did. Injection medialization had the highest PΔmax and tracheoscopy the lowest. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1580-E1588, 2021.

N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study.

BACKGROUND: Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth. METHODS: Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). RESULTS: About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects. CONCLUSION: We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy.