A Critical Role for HlgA in Staphylococcus aureus Pathogenesis Revealed by A Switch in the SaeRS Two-Component Regulatory System.

Cytolytic pore-forming toxins including alpha hemolysin (Hla) and bicomponent leukotoxins play an important role in the pathogenesis of Staphylococcus aureus. These toxins kill the polymorphonuclear phagocytes (PMNs), disrupt epithelial and endothelial barriers, and lyse erythrocytes to provide iron for bacterial growth. The expression of these toxins is regulated by the two-component sensing systems Sae and Agr. Here, we report that a point mutation (L18P) in SaeS, the histidine kinase sensor of the Sae system, renders the S. aureus Newman hemolytic activity fully independent of Hla and drastically increases the PMN lytic activity. Furthermore, this Hla-independent activity, unlike Hla itself, can lyse human erythrocytes. The Hla-independent activity towards human erythrocytes was also evident in USA300, however, under strict agr control. Gene knockout studies revealed that this Hla-independent Sae-regulated activity was entirely dependent on gamma hemolysin A subunit (HlgA). In contrast, hemolytic activity of Newman towards human erythrocytes from HlgAB resistant donors was completely dependent on agr. The culture supernatant from Newman S. aureus could be neutralized by antisera against two vaccine candidates based on LukS and LukF subunits of Panton-Valentine leukocidin but not by an anti-Hla neutralizing antibody. These findings display the complex involvement of Sae and Agr systems in regulating the virulence of S. aureus and have important implications for vaccine and immunotherapeutics development for S. aureus disease in humans.

Efficiency of piezotome-corticision assisted orthodontics in alleviating mandibular anterior crowding-a randomized clinical trial.

OBJECTIVES: The aim of this clinical trial was to investigate the duration of mandibular-crowding alleviation with piezotome-corticision orthodontics compared with conventional orthodontics. DESIGN: Single-centre, two-arm parallel group randomized controlled trial. SETTING: Orthodontic clinic at the University of Connecticut. ETHICAL APPROVAL: The study was approved by the Institutional Review Board (IRB # 12-0147-2). SUBJECTS AND METHODS: Forty-one adult subjects from a single centre with more than 5mm of mandibular anterior crowding were randomly allocated using block randomization into experimental and control groups. The experimental group received a corticision procedure with a piezotome on the labial aspect of the mandibular incisors in conjunction to a self-ligation fixed orthodontic appliance. The control group received the self-ligation fixed orthodontic appliance and no corticision. Same archwire sequence (0.014 inch followed by 0.014 × 0.025 inch copper-nickel-titanium) was followed for both groups. Mandibular study casts taken every 4-5 weeks were used to assess changes in the irregularity index by blinded outcome assessors. OUTCOME MEASURES: The time to alignment was calculated in days. RESULTS: Twenty-nine subjects (16 experimental and 13 control) completed the study. Overall, no significant difference in the time required to correct mandibular crowding with piezotome-corticision assisted (102.1 ± 34.7 days; 95% CI, 83.6 to 120.6) and conventional orthodontics (112 ± 46.2 days; 95% CI, 84-139.9) was observed. No complications with treatment or unintended consequences were observed on any of the subjects. LIMITATIONS: A high attrition rate. CONCLUSIONS: This randomized clinical trial found no evidence that piezotome-corticision assisted orthodontics was more efficient in alleviating mandibular anterior crowding. REGISTRATION: ClinicalTrials.gov, Identifier: NCT02026258. FUNDING: Division of Orthodontics, University of Connecticut. CONFLICT OF INTEREST: None.

Failure rates of mini-implants placed in the infrazygomatic region.

BACKGROUND: The purpose of this pilot study was to evaluate the failure rates of mini-implants placed in the infrazygomatic region and to evaluate factors that affect their stability. METHODS: A retrospective cohort study of 30 consecutive patients (55 mini-implants) who had infrazygomatic mini-implants at a University Clinic were evaluated for failure rates. Patient, mini-implant, orthodontic, surgical, and mini-implant maintenance factors were evaluated by univariate logistic regression models for association to failure rates. RESULTS: A 21.8 % failure rate of mini-implants placed in the infazygomatic region was observed. None of the predictor variables were significantly associated with higher or lower odds for failed implants. CONCLUSIONS: Failure rates for infrazygomatic mini-implants were slightly higher than those reported in other maxilla-mandibular osseous locations. No predictor variables were found to be associated to the failure rates.

Dental enamel: genes define biomechanics.

Regulated gene expression assembles an extracellular proteinaceous matrix to control biomineralization and the resultant biomechanical function of tooth enamel. The importance of the dominant enamel matrix protein, amelogenin (Amel); a minor transiently expressed protein, dentin sialoprotein (Dsp); an electrogenic sodium bicarbonate cotransporter (NBCe1); the timely removal of the proteinaceous matrix by a serine protease, Kallikrein-4 (Klk4); and the late-stage expression of Amelotin (Amtn) on enamel biomechanical function were demonstrated and measured using mouse models.