MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of ß-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD) precursors, nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) extend healthspan and ameliorate some age-related conditions in model organisms. However, early-phase trials of NAD precursors have yielded varying results and their pharmacokinetics remain incompletely understood. Here, we report the pharmacokinetics and pharmacodynamics of MIB-626, a microcrystalline unique polymorph ßNMN formulation. METHODS: In this double-blind, placebo-controlled study, 32 overweight or obese adults, 55-80 years, were block-randomized, stratified by sex, to 1 000-mg MIB-626 once daily, twice daily, or placebo for 14 days. NMN, NAD, and NAD metabolome were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Participant characteristics were similar across groups. MIB-626 was well tolerated and frequency of adverse events was similar across groups. Blood NMN concentrations on Day 14 in MIB-626-treated groups were significantly higher compared to placebo (1.7-times and 3.7-times increase above baseline in 1 000 mg once-daily and twice-daily groups in mean AUClast, respectively). MIB-626 treatment was associated with substantial dose-related increases in blood NAD levels. Blood levels of NAD metabolites were higher in NMN-treated participants on Days 8 and 14 than at baseline. Changes in NMN or NAD levels were not related to sex, body mass index, or age. Very little unmodified NMN was excreted in the urine. CONCLUSION: MIB-626 1 000 mg once-daily or twice-daily regimens were safe and associated with substantial dose-related increases in blood NAD levels and its metabolome. These foundational data that were obtained using a pharmaceutical-grade ßNMN, standardized sample collection, and validated liquid chromatography-tandem mass spectrometry assays, should facilitate design of efficacy trials in disease conditions.

Does Smear Layer Removal Influence Root Canal Therapy Outcome? A Systematic Review.

OBJECTIVE: The aim of this systematic review was to determine whether the smear layer (SL) removal procedure influences the outcome of root canal treatment. STUDY DESIGN: We performed a search on Pubmed, Scopus, ISI Web of Science, Cochrane Library, Lilacs and SIGLE. We included randomized controlled clinical trials (RCT), with clinical and radiographic outcomes, conducted on subjects who had undergone root canal therapy. The protocol differed only in the SL removal or maintenance procedure. We evaluated the papers for risk of bias according to the Cochrane assessment tool. RESULTS: A total of 1,983 articles were found, after removal of duplicates, 892 remained. We included two studies in this review. One study revealed a low risk of bias and a high success rate for the SL removal group compared to the non SL removal group (P = 0.04), while the other study had a high risk of bias and found no difference between the SL removal and non SL removal groups (P = 1.00). CONCLUSION: We concluded that the SL removal for root canal treatment of primary teeth with initial clinical signs and symptoms or pulpal necrotic status, could benefit the outcome, although further RCT should be performed to achieve evidence.