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Objective To assess upper airway volume changes after rapid maxillary expansion (RME) with three different expanders. Trial design Three-arm parallel randomized clinical trial. Methods Sixty-six patients, 10–16 years old, in permanent dentition, with maxillary transverse deficiency were recruited and assigned with block randomization (1:1:1 ratio) and allocation concealment to three groups of 22 patients each (Hyrax, Hybrid-Hyrax, and Keles keyless expander). The primary outcome (overall upper airway volume change) and secondary outcomes (volume changes in the nasal cavity, nasopharynx, oropharynx, and hypopharynx) were blindly assessed on the initial (T0) and final (T1, 6 months at appliance removal) cone beam computed tomography. Differences across groups were assessed with crude or adjusted for confounders (gender, age, growth stage, skeletal pattern, baseline airway volume, and amount of expansion) linear regression models. Results Fifty-one patients were analysed (19, 19, and 13 in the Hyrax, Hybrid-Hyrax, and Keles groups). Maxillary expansion resulted in considerable increases in total airway volume in the Hybrid-Hyrax group (+5902.1 mm3) and less in the Hyrax group (+2537.9 mm3) or the Keles group (+3001.4 mm3). However, treatment-induced changes for the primary and all secondary outcomes were of small magnitude and no significant difference was seen among the three expanderes in the total airway volume in either crude or adjusted analyses (P > 0.05 in all instances). Finally, among pre-peak patients (CVM 1–3), the Hybrid-Hyrax expander was associated with significantly greater increases in total airway volume compared to the Hyrax expander (P = 0.02). Conclusions RME resulted in relatively small increases in total upper airway volume and its separate compartments, with mostly no statistically significant differences across the Hyrax, Hybrid-Hyrax, and Keles groups. Limitations Significantly greater attrition was found in the Keles group due to appliance failure. The current trial might possibly be under-powered to detect differences between groups, if such exist. Harms Keles expanders blocked during activations and required substitution for completion of treatment. Protocol The protocol was not published before trial commencement. Registration Australian and New Zealand Clinical Trial Registry (ACTRN12617001136392). [ABSTRACT FROM AUTHOR]

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB to S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains. Many isolates of the predominant Asian community-associated methicillin-resistant S. aureus lineage sequence type (ST) 59 harbor seb, implying a significant role of SEB in the observed hypervirulence of this lineage. We created an isogenic seb mutant in a representative ST59 isolate and assessed its virulence potential in mouse infection models. We detected a significant contribution of seb to systemic ST59 infection that was associated with a cytokine storm. Our results directly demonstrate that seb contributes to S. aureus pathogenesis, suggesting the value of including SEB as a target in multipronged antistaphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of community-associated methicillin-resistant S. aureus infection. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection. Here we show that the Staphylococcus aureus Pmt ABC transporter defends the bacteria from killing by important human AMPs and elimination by human neutrophils. By showing that Pmt contributes to virulence during skin infection in an AMP-dependent manner, we provide evidence that AMP resistance plays a key role in bacterial infection. [ABSTRACT FROM AUTHOR]

Community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) are on a global rise. However, analysis of virulence characteristics has been limited almost exclusively to the US endemic strain USA300. CA-MRSA strains that do not produce Panton-Valentine leukocidin (PVL) have not been investigated on a molecular level. Therefore, we analyzed virulence determinants in a PVL-negative CA-MRSA strain, ST72, from Korea. Genome-wide analysis identified 3 loci that are unique to that strain, but did not affect virulence. In contrast, phenol-soluble modulins (PSMs) and the global virulence regulator Agr strongly affected lysis of neutrophils and erythrocytes, while α-toxin and Agr had a major impact on in vivo virulence. Our findings substantiate the general key roles these factors play in CA-MRSA virulence. However, our analyses also showed noticeable differences to strain USA300, inasmuch as α-toxin emerged as a much more important factor than PSMs in experimental skin infection caused by ST72. [ABSTRACT FROM AUTHOR]

Phenol-soluble modulins (PSMs) are a recently discovered family of amphipathic, alpha-helical peptides that have multiple roles in staphylococcal pathogenesis and contribute to a large extent to the pathogenic success of virulent staphylococci, such as Staphylococcus aureus. PSMs may cause lysis of many human cell types including leukocytes and erythrocytes, stimulate inflammatory responses, and contribute to biofilm development. PSMs appear to have an original role in the commensal lifestyle of staphylococci, where they facilitate growth and spreading on epithelial surfaces. Aggressive, cytolytic PSMs seem to have evolved from that original role and are mainly expressed in highly virulent S. aureus. Here, we will review the biochemistry, genetics, and role of PSMs in the commensal and pathogenic lifestyles of staphylococci, discuss how diversification of PSMs defines the aggressiveness of staphylococcal species, and evaluate potential avenues to target PSMs for drug development against staphylococcal infections. [ABSTRACT FROM AUTHOR]