Faculty Bibliography

Introduction: Non-tuberculous mycobacteria (NTM) is an intracellular microorganism that causes cavitary disease and nodular bronchiectatic disease of the lung. Patients with NTM appear to have impaired swallow function as represented by impaired airway protection and pharyngeal bolus clearance. It is unknown whether impaired swallowing contributes to the pathophysiology of NTM. Our aim is to determine swallow physiology in patients with bronchiectasis and NTM compared with a control group.
Method(s): Video fluoroscopy (VF) was prospectively collected from 195 patients: 132 patients with NTM (90 females; ages 30-90) and 63 agematched and sex-matched controlswith noNTM(39 females; ages 27-92). Two boluses of 3, 5, 10ml thin liquid, two 5ml puree Varibar, and cracker were analyzed per subject (N = 1755 swallows). Outcome measures included ordinal ratings of residue in the valleculae and pyriform sinuses.
Result(s): Inter-and intra-rater reliability of the ordinal ratings were assessed using one-way mixed intraclass correlation coefficients (ICC) (ICC(2,1)) on 20% of the data with good results (intra-rater: ICC = 0.92, 95% range CI 0.70-0.97 and inter-rater: ICC = 0.92, 95% range CI 0.81-0.97). The ratings of residue in the valleculae were significantly higher (worse) in the NTM group compared to the control group for one of the 3mL bolus (p = 0.008), for both 5 mL boluses (p = 0.009 and p = 0.004), both 10mL boluses (p = 0.0005 and p = 0.0006), puree (p = 0.006), cracker (p = 0.005). The ratings of residue in the pyriform sinuses were also significantly higher in the NTM group for 3 mL boluses (p = 0.0002 and p = 0.01), both 5 mL boluses (p = 0.0003 and p = 0.002), both 10mL boluses (p = 0.001 and p = 0.001), both puree trials (p<0.0001 and p<0.0001).
Conclusion(s): Future work is needed to elucidate responsiveness to swallowing treatment for patients with NTM

In humans and animal models, oxytocin increases social closeness, attachment and prosocial behaviors, while decreasing anxiety and stress levels. Efficiently triggering the release of endogenous oxytocin could serve as a powerful therapeutic intervention for disorders of social behavior and for anxiety. We designed a new version of a social sensorimotor synchronization task to investigate the role of social approval in inducing biochemical and psychological changes following behavioral synchrony in a sample of 80 college students. Social approval in the form of real time positive feedback increased well-being only in women, while increasing social closeness in both genders. Social disapproval in the form of real time negative feedback prevented a decrease in stress levels that otherwise women reported following engagement in either social or non-social synchronization. Surprisingly, for certain personality traits, negative social feedback during sensorimotor synchronization was psychologically beneficial irrespective of gender. Salivary oxytocin levels increased only in women after the social but not the non-social synchronization tasks. Oxytocin dynamics were independent of the type of real time feedback that subjects received, indicating the existence of distinct mechanisms for hormonal versus behavioral changes following synchronization. Nevertheless, changes in salivary oxytocin after positive social feedback correlated with changes in well-being and predicted changes in prosocial attitudes. Our findings show evidence of distinct mechanisms for behavioral versus hormonal changes following social sensorimotor synchronization, and indicate that gender and personality traits should be carefully considered when designing behavioral therapies for improving social attitudes and for stress management.

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors' platinum resistance identifies novel approach to treating these tumors.

Cochlear implants are one of the most successful neuroprosthetic devices that have been developed to date. Profoundly deaf patients can achieve speech perception after complete loss of sensory input. Despite the improvements many patients experience, there is still a large degree of outcome variability. It has been proposed that central plasticity may be a major factor in the different levels of benefit that patients experience. However, the neural mechanisms of how plasticity impacts cochlear implant learning and the degree of plasticity's influence remain unknown. Here, we review the human and animal research on three of the main ways that central plasticity affects cochlear implant outcomes.