Clinical Trials in Facial Plastic and Reconstructive Surgery.

Many facial plastic and reconstructive surgery providers are interested in incorporating clinical trials into their own practice. Clinical trials in facial plastics have made key contributions to current practices. Clinical trials range from investigating the safety and efficacy of Juvederm filler to reducing pain associated with injecting Juvederm. This article summarizes landmark clinical trials in facial plastic and reconstructive surgery and provides a framework for providers to get involved in clinical trials.

The Microbiology of Acute Exacerbations in Chronic Rhinosinusitis - A Systematic Review.

Background: Acute exacerbations (AE) in chronic rhinosinusitis (CRS) are a common and important clinical issue. However, relatively little is known regarding the underlying microbiology that drives exacerbations or how it relates to the microbiome of CRS. The purpose of this study is to examine the literature to characterize the microbiome associated with acute exacerbations in a chronic rhinosinusitis setting. Understanding this disease process may facilitate targeted antibiotic therapy, reduced antibiotic resistance, and offer more effective disease control and treatment efficacy. Objective: To characterize the microbiome associated with acute exacerbations of chronic rhinosinusitis (AECRS). Methods: We conducted a systematic review of the literature on Medline, Embase, and Web of Science databases from January 1990-June 2021 to identify studies related to AE in CRS. Exclusion criteria include non-English, non-human studies, and case reports. Studies without culture or PCR data were also excluded. Results: Fourteen studies were identified which provided detailed data regarding sinus microbiome in AECRS patients. In these patients, a total of 1252 individual isolates were identified. While common acute pathogens were identified in high frequencies in the sinonasal cultures (Staphylococcus pneumonia, Haemophilus influenza), the predominant bacteria were Staphylococcus aureus (including methicillin-sensitive Staphylococcus aureus) and Pseudomonas aeruginosa. Patient characteristics that may represent higher risk phenotypes were not consistently collected in the studies. Discussion of antimicrobial sensitivities and/or resistance were included in 7/14 studies. Conclusions: This systematic review identifies the predominant microbiology species that may contribute to AECRS. Further studies are needed to understand the pathogenic role of bacteria and viruses in AECRS and to identify associated comorbidities and patient phenotypes that may predispose to AE. The optimal treatment regimen for AECRS remains unclear.

Contextual Role of a Salt Bridge in the Phage P22 Coat Protein I-Domain.

The I-domain is a genetic insertion in the phage P22 coat protein that chaperones its folding and stability. Of 11 acidic residues in the I-domain, seven participate in stabilizing electrostatic interactions with basic residues across elements of secondary structure, fastening the ß-barrel fold. A hydrogen-bonded salt bridge between Asp-302 and His-305 is particularly interesting as Asp-302 is the site of a temperature-sensitive-folding mutation. The pKa of His-305 is raised to 9.0, indicating the salt bridge stabilizes the I-domain by ∼4 kcal/mol. Consistently, urea denaturation experiments indicate the stability of the WT I-domain decreases by 4 kcal/mol between neutral and basic pH. The mutants D302A and H305A remove the pH dependence of stability. The D302A substitution destabilizes the I-domain by 4 kcal/mol, whereas H305A had smaller effects, on the order of 1-2 kcal/mol. The destabilizing effects of D302A are perpetuated in the full-length coat protein as shown by a higher sensitivity to protease digestion, decreased procapsid assembly rates, and impaired phage production in vivo By contrast, the mutants have only minor effects on capsid expansion or stability in vitro The effects of the Asp-302-His-305 salt bridge are thus complex and context-dependent. Substitutions that abolish the salt bridge destabilize coat protein monomers and impair capsid self-assembly, but once capsids are formed the effects of the substitutions are overcome by new quaternary interactions between subunits.