ObjectiveMelanocortin-4 receptors (MC4Rs) are highly expressed by dopamine-secreting neurons of the mesolimbic tract, but their functional role has not been fully resolved. Voluntary wheel running (VWR) induces adaptations in the mesolimbic dopamine system and has a myriad of long-term beneficial effects on health. In the present experiments we asked whether MC4R function regulates the effects of VWR, and whether VWR ameliorates MC4R-associated symptoms of the metabolic syndrome.MethodsElectrically evoked dopamine release was measured in slice preparations from sedentary wild-type and MC4R-deficient Mc4rK314X (HOM) rats. VWR was assessed in wild-type and HOM rats, and in MC4R-deficient loxTBMc4r mice, wild-type mice body weight-matched to loxTBMc4r mice, and wild-type mice with intracerebroventricular administration of the MC4R antagonist SHU9119. Mesolimbic dopamine system function (gene/protein expression) and metabolic parameters were examined in wheel-running and sedentary wild-type and HOM rats.ResultsSedentary obese HOM rats had increased electrically evoked dopamine release in several ventral tegmental area (VTA) projection sites compared to wild-type controls. MC4R loss-of-function decreased VWR, and this was partially independent of body weight. HOM wheel-runners had attenuated markers of intracellular D1-type dopamine receptor signaling despite increased dopamine flux in the VTA. VWR increased and decreased ΔFosB levels in the nucleus accumbens (NAc) of wild-type and HOM runners, respectively. VWR improved metabolic parameters in wild-type wheel-runners. Finally, moderate voluntary exercise corrected many aspects of the metabolic syndrome in HOM runners.ConclusionsCentral dopamine dysregulation during VWR reinforces the link between MC4R function and molecular and behavioral responding to rewards. The data also suggest that exercise can be a successful lifestyle intervention in MC4R-haploinsufficient individuals despite reduced positive reinforcement during exercise training.

Objectives/Hypothesis: To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP).Study Design: Prospective, multi-institutional cohort study.Methods: Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence.Results: The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P < .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P < .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites.Conclusions: RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location.

Background: There is an increasing array of treatment options for addressing clinically significant thyroid nodules, including radiofrequency ablation (RFA). While effective, the cost compared to alternative approaches has not been well elucidated.Methods: This study involved a retrospective chart review, focusing on variable direct cost (VDC) of each procedure, from April 2016 to January 2020. We analyzed costs for 53 open lobectomies and 16 RFA procedures. Results: Cost effectiveness depended on the simulated cost of the RFA probe.In comparison to open lobectomy, the VDC to perform RFA was $597 (19%) cheaper when the simulated probe cost was $1500 and $403 (13%) more expensive for a probe cost of $2500. Statistical significance was achieved for both these differences. Conclusions: If cost per RFA probe can be less than $2100-the break-even dollar amount between open lobectomy and RFA-there would be considerable cost savings for treating thyroid nodules.

Squid processing byproducts and scallop viscera were homogenized and subjected to hydrolysis at 55°C for 1.5 hr, followed by pasteurization at 75°C for 30 min. The respective hydrolysates were incorporated into diets in which 30–70% of fishmeal (FM) was replaced with soybean meal (SBM) and evaluated as is (wet), dried, or impregnated into SBM for their effects on growth of European seabass, Dicentrarchus labrax; California yellowtail, Seriola lalandi; and barramundi, Lates calcarifer, in a series of 8‐week experiments. No adverse thermal deterioration in the quality of hydrolysate occurred because of drum drying, compared to the wet hydrolysate. No differences were observed in growth of California yellowtail between SBM mixed with dry hydrolysate and SBM impregnated with wet hydrolysate. Dietary inclusion of hydrolysate improved feed attractability and growth and was beneficial in the early juvenile stage but not in the growout stage for European seabass and California yellowtail. However, in barramundi, no discernable benefit was observed from the addition of hydrolysates. The improved feed attractability and growth appear to be dependent on species and type of hydrolysate. The texture of fillets of yellowtail fed 70% FM replacement with SBM + squid hydrolysate diets was significantly firmer than without squid hydrolysate.

ImportanceMarked variation in hospital costs and payments is a target for health care reform efforts. Limited data exist to explain variability in prices for head and neck surgical procedures.ObjectiveTo characterize variations in hospital price markup for head and neck cancer surgery, and examine associations with market concentration and hospital for-profit status.Design, Setting, and ParticipantsIn this cross-sectional study, the Nationwide Inpatient Sample was used to identify 150 275 patients who underwent head and neck cancer surgery for a malignant upper aerodigestive tract neoplasm from 2001 to 2011. The markup ratio (charges to costs) was modeled as a continuous and categorical variable. Hospital market concentration was evaluated using a variable-radius Herfindahl-Hirschman Index from the 2000, 2003, 2006, and 2009 Hospital Market Structure files. Data were analyzed from May 2019 to July 2019.Main Outcomes and MeasuresMultivariable regression was used to evaluate associations between hospital and patient variables and hospital markup.ResultsThere were 150 275 patients (mean [SD] age, 61.8 [12.6] years; 104 974 [70.0%] male) from 2001 to 2011 for whom hospital market information was available. Hospital markup ratios ranged from 0.8 to 8.7, with a mean markup ratio of 2.8 (95% CI, 2.7-2.9). Hospitals in the lowest markup ratio quartile had a mean markup ratio of 1.8 (95% CI, 1.8-1.9), while hospitals in the top markup ratio quartile (extreme markup) had a mean markup ratio of 4.1 (95% CI, 4.0-4.2). Extreme markup hospitals were more often large (77.5% vs 66.6%), private for-profit hospitals (19.0% vs 1.3%), and were less likely to be high-volume hospitals (21.0% vs 9.4%) or in competitive markets (64.4% vs 82.0%). Postoperative complications occurred more often in extreme markup hospitals (22.7% vs 17.1%). On multivariate analysis, a significantly higher markup was associated with private, for-profit hospitals (47.9%; 95% CI, 33.3%-64.2%), hospitals in the West (25.5%; 95% CI, 12.6%-39.8%), Hispanic race (9.8%; 95% CI, 4.4%-15.5%), prior radiation therapy (5.3%; 95% CI, 1.3%-9.4%), comorbidity (3.5%; 95% CI, 1.7%-5.4%), and complications (2.8%; 95% CI, 0.3%-5.4%). Hospital market concentration modified the association between hospital for-profit status and markup, with higher markups in for-profit hospitals in moderately concentrated and concentrated (less competitive) markets.Conclusions and RelevanceIn this cross-sectional study, there was wide variation in hospital markup for head and neck cancer surgery, with a 4-fold increase in charges relative to costs in 25% of hospitals. Variations in surgical price were primarily associated with hospital profit status. These data suggest that greater transparency is needed to address disparities in hospital pricing.