Application of sequential multimodal analgesia before and after impacted mandibular third molar extraction: Protocol for a randomized controlled trial.

Background: Several analgesics have been applied under various protocols to control the moderate-to-severe postoperative pain caused by the surgical extraction of an impacted mandibular third molar. However, a consensus on optimal pain management while minimizing side effects is yet to be reached. Methods: This multi-center, prospective, double-blind, randomized controlled trial aims to evaluate the efficacy and safety of sequential multimodal analgesia combined with postoperative zaltoprofen along with multiple preemptive analgesics. A total of 80 participants with bilateral impacted mandibular third molar from two hospitals were randomized into two groups. Two surgical extractions were performed at one-month intervals, and in a crossover design, celecoxib or tramadol/acetaminophen was administered before one extraction and placebo before the other extraction. Following extraction, all subjects took zaltoprofen for 5 days. The outcome measures included pain at specific times, time and intensity of the first pain onset after extraction, need of rescue drugs, and occurrence and frequency of side effects. Conclusions: This ongoing clinical trial was designed to provide evidence regarding a new protocol for effective postoperative pain management of a commonly performed surgical extraction. The results of this study will provide guidance to clinicians regarding the timing and combination of oral analgesics in various oral surgeries performed under local anesthesia. Trial registration: KCT0005450, registered on October 7, 2020.

Topical Administration of Melatonin-Loaded Extracellular Vesicle-Mimetic Nanovesicles Improves 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis.

Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial exposure. Although melatonin has an excellent biosafety profile and a potential to treat AD, there is limited clinical evidence from controlled trials that support the use of melatonin as an AD treatment. The delivery of melatonin via the transdermal delivery system is also a challenge in designing melatonin-based AD treatments. In this study, we generated melatonin-loaded extracellular vesicle-mimetic nanoparticles (MelaNVs) to improve the transdermal delivery of melatonin and to evaluate their therapeutic potential in AD. The MelaNVs were spherical nanoparticles with an average size of 100 nm, which is the optimal size for the transdermal delivery of drugs. MelaNVs showed anti-inflammatory effects by suppressing the release of TNF-α and ß-hexosaminidase in LPS-treated RAW264.7 cells and compound 48/80-treated RBL-2H3 cells, respectively. MelaNVs showed a superior suppressive effect compared to an equivalent concentration of free melatonin. Treating a 2,4-dinitrofluorobenzene (DNCB)-induced AD-like mouse model with MelaNVs improved AD by suppressing local inflammation, mast cell infiltration, and fibrosis. In addition, MelaNVs effectively suppressed serum IgE levels and regulated serum IFN-γ and IL-4 levels. Taken together, these results suggest that MelaNVs are novel and efficient transdermal delivery systems of melatonin and that MelaNVs can be used as a treatment to improve AD.

Organogermanium Nanowire Cathodes for Efficient Lithium-Oxygen Batteries.

We report a technique for effectively neutralizing the generation of harmful superoxide species, the source of parasitic reactions, in lithium-oxygen batteries to generate stable substances. In organic electrolytes, organogermanium (Propa-germanium, Ge-132) nanowires can suppress solvated superoxide and induce strong surface-adsorption reaction due to their high anti-superoxide disproportionation activity. Resultantly, the effect of organogermanium nanowires mitigate toxic oxidative stress to stabilize organic electrolytes and promote good Li2O2 growth. These factors led to long duration of the electrolytes and impressive rechargeability of lithium-oxygen batteries.