Two structurally related fluorescent imaging probes allow optical imaging of bacterial leg infection models in living athymic and immunocompetent mice. Structurally, the probes are comprised of a deep-red fluorescent squaraine rotaxane scaffold with two appended bis(zinc(II)-dicolylamine) (bis(Zn-DPA)) targeting ligands. The bis(Zn-DPA) ligands have high affinity for the anionic phospholipids and related biomolecules that reside within the bacterial envelope, and they are known to selectively target bacterial cells over the nearly uncharged membrane surfaces of healthy mammalian cells. Planar, whole-animal optical imaging studies showed that intravenous dosing of either probe (10 nmol) allowed imaging of localized infections of Grampositive Staphylococcus aureus and Gram-negative Salmonella enterica serovar typhimurium. High selectivity for the infected target leg (T) over the contralateral non-target leg (NT) was reflected by T/NT ratios up to six. The infection imaging signal was independent of mouse humoral immune status, and there was essentially no targeting at a site of sterile inflammation induced by injection of λ-carrageenan. Furthermore, the fluorescent probe imaging signal colocalized with the bioluminescence signal from a genetically engineered strain of S. enterica serovar typhimurium. Although not highly sensitive (the localized infection must contain at least 10 6 colony forming units for fluorescence visualization) the probes are remarkably selective for bacterial cells considering their low molecular weight (<1.5 kDa) and simple structural design. The more hydrophilic of the two probes produced a higher T/NT ratio in the early stages of the imaging experiment and washed out more rapidly from the blood clearance organs (liver, kidney). Therefore, it is best suited for longitudinal studies that require repeated dosing and imaging of the same animal. The results indicate that fluorescent probes based on squaraine rotaxanes should be broadly useful for in vivo animal imaging studies, and they further validate the ability of imaging probes with bis(Zn-DPA) ligands to selectively target bacterial infections in living animals.

Cochlear implantation in unilateral sudden hearing loss with a normal functioning contralateral ear might prove to be an effective therapy. Tinnitus is reduced as is the signal-to-noise ratio, which still allows 50% speech discrimination. All patients felt that they localized sound better, and most felt that they understood speech better. Further studies should be conducted to compare the success of hearing rehabilitation of cochlear rehabilitation and traditional modalities such as contralateral routing of signal and bone-anchored hearing aids.

Despite a considerable expansion in our therapeutic repertoire for management of other malignancies, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Upon normalizing National Institutes of Health-awarded R01 and R01-equivalent grants by incidence, thyroid cancer ($214) and HNC ($1329) received the fewest funding dollars. Upon adjusting funding totals by mortality, HNC was 7th out of 9 cancers evaluated ($6138). These findings highlight HNC as an underfunded disease versus other cancers. As data detailing grant applications (including unsuccessful grants) are not publicly available, it is not clear if these disparities stem from fewer applications or fewer opportunities. Our hope is that this commentary will spur further investigation into strategies to increase HNC inquiry and funding for trainees as well as early-stage and established investigators.

These findings reinforce the importance of supporting further HNSCC drug discovery as modern treatment strategies using systemic therapy have resulted in measurable improvements in oncologic outcomes. Laryngoscope, 127:2565-2569, 2017.

No abstract