A Conditioned Behavioral Paradigm for Assessing Onset and Lasting Tinnitus in Rats

Numerous behavioral paradigms have been developed to assess tinnitus-like behavior in animals. Nevertheless, they are often limited by prolonged training requirements, as well as an inability to simultaneously assess onset and lasting tinnitus behavior, tinnitus pitch or duration, or tinnitus presence without grouping data from multiple animals or testing sessions. To enhance behavioral testing of tinnitus, we developed a conditioned licking suppression paradigm to determine the pitch(s) of both onset and lasting tinnitus-like behavior within individual animals. Rats learned to lick water during broadband or narrowband noises, and to suppress licking to avoid footshocks during silence. After noise exposure, rats significantly increased licking during silent trials, suggesting onset tinnitus-like behavior. Lasting tinnitus-behavior, however, was exhibited in about half of noise-exposed rats through 7 weeks post-exposure tested. Licking activity during narrowband sound trials remained unchanged following noise exposure, while ABR hearing thresholds fully recovered and were comparable between tinnitus(+) and tinnitus(-) rats. To assess another tinnitus inducer, rats were injected with sodium salicylate. They demonstrated high pitch tinnitus-like behavior, but later recovered by 5 days post-injection. Further control studies showed that 1): sham noise-exposed rats tested with footshock did not exhibit tinnitus-like behavior, and 2): noise-exposed or sham rats tested without footshocks showed no fundamental changes in behavior compared to those tested with shocks. Together, these results demonstrate that this paradigm can efficiently test the development of noise- and salicylate-induced tinnitus behavior. The ability to assess tinnitus individually, over time, and without averaging data enables us to realistically address tinnitus in a clinically relevant way. Thus, we believe that this optimized behavioral paradigm will facilitate investigations into the mechanisms of tinnitus and development of effective treatments

Primary Hurthle cell thyroid carcinoma treated with surgery: A single institution experience of 92 patients

https://openworks.mdanderson.org/sumexp23/1062/thumbnail.jp

Bleeding risk associated with resection of the middle turbinate during functional endoscopic sinus surgery

BACKGROUND: The decision to resect the middle turbinate (MT) during functional endoscopic sinus surgery is controversial. Although there have been a variety of studies that examined the functional outcome related to this maneuver, very few studies evaluated the potential for complications, in particular, epistaxis. OBJECTIVE: We sought to determine if resection of the MT during functional endoscopic sinus surgery leads to an increased risk for postoperative bleeding. METHODS: Patients who underwent functional endoscopic sinus surgery for chronic sinusitis or nasal polyposis between 2004 and 2014 at a single institution were analyzed for bleeding and other complications after resection of the MT. RESULTS: Between 2004 and 2014, 1185 sinus surgeries were performed by 18 surgeons. A propensity matched set of 228 patients who underwent turbinate resection, and 228 controls were selected based on predicted probabilities from a logistic regression that predicted turbinate resection and that was adjusted for age, sex, and procedure. There were 89 patients with bilateral turbinates removed and 139 with unilateral turbinates removed. There was no significant difference in major bleeding or other complication rates between the two groups. Patients who underwent resection of at least one MT were 3.95 times more likely to have minor bleeding compared with those who did not; this risk increased with the number of turbinates resected (trend p = 0.008). Patients on anticoagulation medications were at a significant risk of bleeding if their MT was removed (p = 0.007), whereas patients on aspirin or antiplatelet therapy were not at a significant risk. CONCLUSION: There was no increased risk of major bleeding or other complication associated with resection of the MT. However, there was a significantly increased minor bleeding rate associated with MT resection, particularly if the patient was on anticoagulants

Top and side views of the behavioral testing chamber.

<p>The horizontal waterspout is located in the front of the wire mesh chamber and connected to a syringe pump for water delivery. Speakers were mounted to the chamber walls on both sides of the waterspout, so that sound could be presented bilaterally to the animal. Sounds levels and frequencies were calibrated using a microphone (ACO Pacific, Belmont, CA) and the chamber was tested to ensure that sound presentation did not vibrate the chamber. The stainless steel grid floor was electrified to deliver footshocks. Behavioral sessions were monitored with a USB camera placed above the testing chamber.</p

ABR hearing thresholds for tinnitus⁽⁺⁾, tinnitus^(-), and control rats prior to intense noise or sham exposure, and on post-exposure day 0 and post-exposure week 7.

<p>Thresholds were elevated across all frequencies in tinnitus⁽⁺⁾ and tinnitus^(-) rats at post-exposure day 0, revealing immediate and significant hearing loss. By post-exposure week 7, however, thresholds recovered to pre-exposure levels. At all time points, thresholds were similar between tinnitus⁽⁺⁾ and tinnitus^(-) rats. There were no threshold elevations in control rats. Error bars represent standard error of the mean.</p

Licking rates during silent trials prior to injections (post-exposure week 8), as well as 3 hours and 5 days following saline (A) or salicylate (B) injections.

<p>After saline injections, no changes in licking rate were observed. Three hours following salicylate injections, however, all nine animals increased licking behavior during silent trials, though most robustly following high-frequency narrowband sound trials. The licking rates during silent trials returned to pre-injection levels by 5 days post-injection.</p

Baseline licking rates of eventual tinnitus⁽⁺⁾, tinnitus^(-), and control (ctrl) rats during different narrowband sound trials (A-E).

<p>Tinnitus^<b>(+)</b> refers to rats that later exceeded 1 lick/trial for one or more silent trial categories over weeks 5 through 7 weeks following noise exposure; tinnitus^<b>(-)</b> refers to noise-exposed rats that did not meet that criteria. For all rats, licking rates did not significantly change between training sessions 14 through 16. These rates were comparable between all groups of rats.</p

Licking rates over time for tinnitus⁽⁺⁾, tinnitus^(-), and control rats during narrowband sound trials (A-E).

<p>Tinnitus^<b>(+)</b> refers to rats that later exceeded 1 lick/trial for one or more silent trial categories over weeks 5 through 7 weeks following noise exposure; tinnitus^<b>(-)</b> refers to noise-exposed rats that did not meet that criteria. No significant changes in sound trial licking were observed for any group of rats.</p

Illustrations showing phase 4 behavioral training during 6–8 and 10–12 kHz sound and silent trials.

<p>The “x 3” and “x 1” notations refer to the number of spout licks required to obtain a water reward and a variable shock, respectively.</p

Baseline rates of licking during silent trials (training sessions 11–16).

<p>Tinnitus^<b>(+)</b> refers to rats that later exceeded 1 lick/trial for one or more silent trial categories over weeks 5 through 7 week following noise exposure; tinnitus^<b>(-)</b> refers to noise-exposed rats that did not meet that criteria. A silent trial category was determined by the narrowband sound trial that preceded it (i.e. 6–8 kHz, 10–12 kHz, 14–16 kHz, 22–24 kHz, 30–32 kHz) (A-E). From baseline test sessions 13–16, all rats exhibited stable baseline behavior (≤ 1 average lick/trial) for every silent trial category, as indicated by the dashed line and shaded area. There were no significant differences between tinnitus⁽⁺⁾, tinnitus^(-), or control (ctrl) rats in baseline silent trial licking.</p