Darren Smith

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen‐agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator‐led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)‐induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U‐shaped response curve with the greatest effect seen at 0.1 μM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen‐agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models.

The synthesis of 1-butyl-2,3-dimethyl-4-vinylimidazolium triflate, its polymerization, and ion exchange to yield a trio of 1-butyl-2,3-dimethyl-4-vinylimidazolium polymers is described. Irrespective of the nature of the anion, substitution at the 2-position of the imidazolium moiety substantially increases the distance between the anion and cation. The methyl substituent at the 2-position also served to expose the importance of H-bonding for the attractive potential between imidazolium moiety and anions in polymers without a methyl group at the 2-position. The thermal characteristics of poly(1-butyl-2,3-dimethyl-4-vinylimidazolium) salts and corresponding poly(1-ethyl-3-methyl-4-vinylimidazolium) salts were evaluated. While the mid-point glass transition temperatures, T_g-mid, for 1-ethyl-3-methyl-4-vinylimidazolium polymers with CF₃SO₃⁻, (CF₃SO₂)₂N⁻ and PF₆⁻ counterions, were 153 °C, 88 °C and 200 °C, respectively, the T_g-mid values for 1-butyl-2,3-dimethyl-4vinylimidazolium polymers with corresponding counter-ions were tightly clustered at 98 °C, 99 °C and 84 °C, respectively. This dramatically reduced influence of the anion type on the glass transition temperature was attributed to the increased distance between the center of the anions and cations in the 1-butyl-2,3-dimethyl-4-vinylimidazolium polymer set, and minimal H-bonding interactions between the respective anions and the 1-butyl-2,3-dimethyl-4-vinylimidazolium moiety. It is believed that this is the first observation of substantial independence of the glass transition of an ionic polymer on the nature of its counterion.

Background: Erich arch bars facilitate intermaxillary fixation, and traditional teaching questions and often argues against the use of arch bars in patients during primary and mixed dentition. Dental anatomy, risk of tooth avulsion, and potential disruption of developing permanent dentition are reasons cited. This study provides the only outcome data on the use of arch bars in children during primary and mixed dentition. Methods: Patients in primary and mixed dentition presenting with mandible fractures treated with arch bars from 2000 to 2010 were reviewed. Elements collected included demographics, medical history, fracture management, adverse outcomes, and dental health as determined by a pediatric dentist at follow-up. Results: A total of 154 mandible fractures in 79 patients were identified, with 23 patients (48 fractures) meeting inclusion criteria. Average age at injury was 9.10 years (range, 2.70 to 13.49 years), and average follow-up was 32.35 months (range, 0.43 to 131.84 months). Fracture types included condylar head (n = 9), condylar neck (n = 12), angle (n = 10), body (n = 4), and parasymphysis (n = 13) fractures. There were no periodontal defects, tooth avulsions, or disturbances to permanent dentition noted with regard to arch bar use. Conclusions: These data demonstrate that arch bars can be safely used in children during primary and mixed dentition with no periodontal defects, tooth avulsions, or disturbances to permanent dentition. Despite traditional teaching, the authors demonstrate arch bar use to be efficacious and safe in children during primary or mixed dentition. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.