Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3β:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.

Limited toxicity data on electronic cigarette (ECIG) impede evidence-based policy recommendations. We compared two popular mixed fruit flavored ECIG-liquids with and without nicotine aerosolized at 40 W (E-smoke) with respect to particle number concentrations, chemical composition, and response on physiologically relevant human bronchial and alveolar lung mucosa models cultured at air–liquid interface. E-smoke was characterized by significantly increased particle number concentrations with increased wattage (25, 40, and 55 W) and nicotine presence. The chemical composition of E-smoke differed across the two tested flavors in terms of cytotoxic compounds including p-benzoquinone, nicotyrine, and flavoring agents (for example vanillin, ethyl vanillin). Significant differences in the expression of markers for pro-inflammation, oxidative stress, tissue injury/repair, alarm anti-protease, anti-microbial defense, epithelial barrier function, and epigenetic modification were observed between the flavors, nicotine content, and/ or lung models (bronchial or alveolar). Our findings indicate that ECIG toxicity is influenced by combination of multiple factors including flavor, nicotine content, vaping regime, and the region of respiratory tree (bronchial or alveolar). Toxic chemicals and flavoring agents detected in high concentrations in the E-smoke of each flavor warrant independent evaluation for their specific role in imparting toxicity. Therefore, multi-disciplinary approaches are warranted for comprehensive safety profiling of ECIG.

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Objectives: Previous studies have shown that hot saline solution (HSS) nasal irrigation is effective against nasal bleeding and is used to treat nasal hemorrhage. In a pilot study, we evaluated hot saline nasal irrigation in comparison to a routinely used nasal packing in terms of self-reported complications and mucosal healing after functional endoscopic sinus surgery.Methods: Patients undergoing surgery for bilateral chronic rhinosinusitis received polyvinyl acetate (PVA) nasal packing in the left nostril, and the right nostril was rinsed with 47 C sterile saline immediately after surgery. Patients' experiences of pain, bleeding, and other types of uncomfortable experiences were measured using a visual analog scale for each nostril before, during, and immediately after nasal packing removal. Two weeks post-surgery, the assessments were repeated including an endoscopic evaluation of the mucosa by the surgeon.Results: Twenty-seven patients completed the study. Prior to removal of the packing, the patients experienced significantly more pain and other uncomfortable experiences in the nostril treated with nasal packing, as compared to the nostril solely rinsed with hot saline. After removal, patients reported significantly more uncomfortable experiences from the packing treated nostril. Two weeks post-surgery, no difference in mucosal healing was observed between the two nostrils. Conclusions:The results from this study indicate that irrigation with HSS could be an alternative postoperative treatment to conventional PVA nasal packing. Hot saline irrigation may contribute to patients experiencing improved control of postoperative bleeding, pain, and less suffering of other causes as well as health-economic benefits, without affecting the mucosal healing up to 2 weeks post-surgery.

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