Endoscopic Versus Microscopic Transcanal Resection of Glomus Tympanicum: A Retrospective Comparative Study.

OBJECTIVE: Comparison of outcomes of microscopic and endoscopic resection of glomus tympanicum (GT) tumors. STUDY DESIGN: Retrospective case review. SETTING: Single tertiary referral center. PATIENTS: All adult patients undergoing transcanal GT resection without mastoidectomy from 2007 to 2021. INTERVENTIONS: Surgical resection-endoscopic versus microscopic approach. MAIN OUTCOME MEASURES: Primary outcomes were tumor recurrence at 1 year and presence of residual tumor at conclusion of surgery. Secondary outcome measures included operative time, postoperative air-bone gap, postoperative symptom resolution, and surgical complications. RESULTS: Thirty-eight patients underwent resection of GT (74% female; mean age, 59 years). Twenty-nine cases were performed microscopically, and nine cases were performed endoscopically. Both endoscopic and microscopic approaches yielded high rates of complete tumor resection (27/29 microscopic cases, 7/9 endoscopic cases). There was no significant difference in mean operative time (2.3 hours for microscopic; 2.6 hours for endoscopic). On average, air-bone gaps (ABGs) decreased by 6.3 dB after endoscopic resection compared with 1.0 dB after microscopic resection ( p = 0.064). No patients were found to have tumor recurrence during an average follow-up interval of 21 months. CONCLUSIONS: These results suggest comparable outcomes with both endoscopic and microscopic approaches for GT resection, and decisions regarding preferred approach should be dictated by surgeon preference.

Relative predictive value of sociodemographic factors for chronic diseases among All of Us participants: a descriptive analysis.

BACKGROUND: Although sociodemographic characteristics are associated with health disparities, the relative predictive value of different social and demographic factors remains largely unknown. This study aimed to describe the sociodemographic characteristics of All of Us participants and evaluate the predictive value of each factor for chronic diseases associated with high morbidity and mortality. METHODS: We performed a cross-sectional analysis using de-identified survey data from the All of Us Research Program, which has collected social, demographic, and health information from adults living in the United States since May 2018. Sociodemographic data included self-reported age, sex, gender, sexual orientation, race/ethnicity, income, education, health insurance, primary care provider (PCP) status, and health literacy scores. We analyzed the self-reported prevalence of hypertension, coronary artery disease, any cancer, skin cancer, lung disease, diabetes, obesity, and chronic kidney disease. Finally, we assessed the relative importance of each sociodemographic factor for predicting each chronic disease using the adequacy index for each predictor from logistic regression. RESULTS: Among the 372,050 participants in this analysis, the median age was 53 years, 59.8% reported female sex, and the most common racial/ethnic categories were White (54.0%), Black (19.9%), and Hispanic/Latino (16.7%). Participants who identified as Asian, Middle Eastern/North African, and White were the most likely to report annual incomes greater than $200,000, advanced degrees, and employer or union insurance, while participants who identified as Black, Hispanic, and Native Hawaiian/Pacific Islander were the most likely to report annual incomes less than $10,000, less than a high school education, and Medicaid insurance. We found that age was most predictive of hypertension, coronary artery disease, any cancer, skin cancer, diabetes, obesity, and chronic kidney disease. Insurance type was most predictive of lung disease. Notably, no two health conditions had the same order of importance for sociodemographic factors. CONCLUSIONS: Age was the best predictor for the assessed chronic diseases, but the relative predictive value of income, education, health insurance, PCP status, race/ethnicity, and sexual orientation was highly variable across health conditions. Identifying the sociodemographic groups with the largest disparities in a specific disease can guide future interventions to promote health equity.

Surgical Management and Outcomes of Pediatric Congenital Head and Neck Teratomas: A Scoping Review.

Objective: To perform a scoping review to characterize postoperative outcomes of pediatric patients (ages 0-18) with a history of congenital head and neck teratomas. Data Sources: PubMed, EMBASE, Web of Science, Cochrane, Clinicaltrails.gov. Review Methods: A search of multiple databases was performed. Studies were included if they detailed the surgical management and outcomes of pediatric patients with a history of congenital head and neck teratomas. Results: One hundred and eight studies totaling 137 patients were identified. The median gestational age at birth was 37 weeks. Respiratory distress, prompting emergent endotracheal intubation or tracheostomy, was present in most patients (58%). The ex utero intrapartum treatment (EXIT) procedure was utilized for 21 (15%) patients. The teratomas were resected after a median duration of 4 days from birth. The most common postsurgical complications were vocal cord paralysis (3%), hemorrhage (2%), and tracheomalacia (2%). Death occurred perioperatively in 2 patients (2%). Twenty-six patients (19%) required additional surgery, and 5 patients (4%) needed adjuvant chemotherapy. Patients were monitored for a median duration of 24 months with a recurrence rate of 6%. Four recurrent cases (50%) had intracranial extension, and 88% of the recurrent cases were mature teratomas at initial histopathological diagnosis. Conclusion: Most patients with congenital head and neck teratomas require emergent airway management perinatally. Excisional and surgical complications are rare, and most patients are cured of their disease with a single operation. Recurrent teratomas tend to have an intracranial extension and are likely to be of mature pathology at the time of initial diagnosis.

Cholinergic modulation of sensory perception and plasticity.

Sensory systems are highly plastic, but the mechanisms of sensory plasticity remain unclear. People with vision or hearing loss demonstrate significant neural network reorganization that promotes adaptive changes in other sensory modalities as well as in their ability to combine information across the different senses (i.e., multisensory integration. Furthermore, sensory network remodeling is necessary for sensory restoration after a period of sensory deprivation. Acetylcholine is a powerful regulator of sensory plasticity, and studies suggest that cholinergic medications may improve visual and auditory abilities by facilitating sensory network plasticity. There are currently no approved therapeutics for sensory loss that target neuroplasticity. This review explores the systems-level effects of cholinergic signaling on human visual and auditory perception, with a focus on functional performance, sensory disorders, and neural activity. Understanding the role of acetylcholine in sensory plasticity will be essential for developing targeted treatments for sensory restoration.

Glutamate Receptors Mediate Changes to Dendritic Mitochondria in Neurons Grown on Stiff Substrates.

The stiffness of brain tissue changes during development and disease. These changes can affect neuronal morphology, specifically dendritic arborization. We previously reported that N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors regulate dendrite number and branching in a manner that is dependent on substrate stiffness. Since mitochondria affect the shape of dendrites, in this study, we determined whether the stiffness of substrates on which rat hippocampal neurons are grown affects mitochondrial characteristics and if glutamate receptors mediate the effects of substrate stiffness. Dendritic mitochondria are small, short, simple, and scarce in neurons cultured on substrates of 0.5 kPa stiffness. In contrast, dendritic mitochondria are large, long, complex, and low in number in neurons grown on substrates of 4 kPa stiffness. Dendritic mitochondria of neurons cultured on glass are high in number and small with complex shapes. Treatment of neurons grown on the stiffer gels or glass with the NMDA and AMPA receptor antagonists, 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively, results in mitochondrial characteristics of neurons grown on the softer substrate. These results suggest that glutamate receptors play important roles in regulating both mitochondrial morphology and dendritic arborization in response to substrate stiffness.

An optimized procedure for robust volitional cocaine intake in mice.

Substance use disorder (SUD) is a behavioral disorder characterized by volitional drug consumption. Mouse models of SUD allow for the use of molecular, genetic, and circuit-level tools, providing enormous potential for defining the underlying mechanisms of this disorder. However, the relevance of results depends on the validity of the mouse models used. Self-administration models have long been the preferred preclinical model for SUD as they allow for volitional drug consumption, thus providing strong face validity. While previous work has defined the parameters that influence intravenous cocaine self-administration in other species-such as rats and primates-many of these parameters have not been explicitly assessed in mice. In a series of experiments, we showed that commonly used mouse models of self-administration, where behavior is maintained on a fixed-ratio schedule of reinforcement, show similar levels of responding in the presence and absence of drug delivery-demonstrating that it is impossible to determine when drug consumption is and is not volitional. To address these issues, we have developed a novel mouse self-administration procedure where animals do not need to be pretrained on sucrose and behavior is maintained on a variable-ratio schedule of reinforcement. This procedure increases rates of reinforcement behavior, increases levels of drug intake, and results in clearer delineation between drug-reinforced and saline conditions. Together, these data highlight a major issue with fixed-ratio models in mice that complicates subsequent analysis and provide a simple approach to minimize these confounds with variable-ratio schedules of reinforcement. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Subcortical T1-Rho MRI Abnormalities in Juvenile-Onset Huntington's Disease.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the huntingtin gene. An increased CAG repeat length is associated with an earlier disease onset. About 5% of HD cases occur under the age of 21 years, which are classified as juvenile-onset Huntington's disease (JOHD). Our study aims to measure subcortical metabolic abnormalities in JOHD participants. T1-Rho (T1ρ) MRI was used to compare brain regions of 13 JOHD participants and 39 controls. Region-of-interest analyses were used to assess differences in quantitative T1ρ relaxation times. We found that the mean relaxation times in the caudate (p < 0.001), putamen (p < 0.001), globus pallidus (p < 0.001), and thalamus (p < 0.001) were increased in JOHD participants compared to controls. Furthermore, increased T1ρ relaxation times in these areas were significantly associated with lower volumes amongst participants in the JOHD group. These findings suggest metabolic abnormalities in brain regions previously shown to degenerate in JOHD. We also analyzed the relationships between mean regional T1ρ relaxation times and Universal Huntington's Disease Rating Scale (UHDRS) scores. UHDRS was used to evaluate participants' motor function, cognitive function, behavior, and functional capacity. Mean T1ρ relaxation times in the caudate (p = 0.003), putamen (p = 0.005), globus pallidus (p = 0.009), and thalamus (p = 0.015) were directly proportional to the UHDRS score. This suggests that the T1ρ relaxation time may also predict HD-related motor deficits. Our findings suggest that subcortical metabolic abnormalities drive the unique hypokinetic symptoms in JOHD.

d-Serine administration affects nitric oxide synthase 1 adaptor protein and DISC1 expression in sex-specific manner.

Antipsychotic medications are inefficient at treating symptoms of schizophrenia (SCZ), and N-methyl d-aspartate receptor (NMDAR) agonists are potential therapeutic alternatives. As such, these agonists may act on different pathways and proteins altered in the brains of patients with SCZ than do antipsychotic medications. Here, we investigate the effects of administration of the antipsychotic haloperidol and NMDAR agonist d-serine on function and expression of three proteins that play significant roles in SCZ: nitric oxide synthase 1 adaptor protein (NOS1AP), dopamine D2 (D2) receptor, and disrupted in schizophrenia 1 (DISC1). We administered haloperidol or d-serine to male and female Sprague Dawley rats via intraperitoneal injection for 12 days and subsequently examined cortical expression of NOS1AP, D2 receptor, and DISC1. We found sex-specific effects of haloperidol and d-serine treatment on the expression of these proteins. Haloperidol significantly reduced expression of D2 receptor in male, but not female, rats. Conversely, d-serine reduced expression of NOS1AP in male rats and did not affect D2 receptor expression. d-serine treatment also reduced expression of DISC1 in male rats and increased DISC1 expression in female rats. As NOS1AP is overexpressed in the cortex of patients with SCZ and negatively regulates NMDAR signaling, we subsequently examined whether treatment with antipsychotics or NMDAR agonists can reverse the detrimental effects of NOS1AP overexpression in vitro as previously reported by our group. NOS1AP overexpression promotes reduced dendrite branching in vitro, and as such, we treated cortical neurons overexpressing NOS1AP with different antipsychotics (haloperidol, clozapine, fluphenazine) or d-serine for 24 h and determined the effects of these drugs on NOS1AP expression and dendrite branching. While antipsychotics did not affect NOS1AP protein expression or dendrite branching in vitro, d-serine reduced NOS1AP expression and rescued NOS1AP-mediated reductions in dendrite branching. Taken together, our data suggest that d-serine influences the function and expression of NOS1AP, D2 receptor, and DISC1 in a sex-specific manner and reverses the effects of NOS1AP overexpression on dendrite morphology.