Faculty Bibliography

The objective of this study was to understand the existing practices and attitudes regarding inpatient sleep at the 2020 US News and World Report (USNWR) Honor Roll pediatric (n = 10) and adult (n = 20) hospitals. Section chiefs of Hospital Medicine from these institutions were surveyed and interviewed between June and August 2021. Among 23 of 30 surveyed physician leaders (response rate = 77%), 96% (n = 22) rated patient sleep as important, but only 43% (n = 10) were satisfied with their institutions' efforts. A total of 96% (n = 22) of institutions lack sleep equity practices. Fewer than half (48%) of top hospitals have sleep-friendly practices, with the most common practices including reducing overnight vital sign monitoring (43%), decreasing ambient light in the wards (43%), adjusting lab and medication schedules (35%), and implementing quiet hours (30%). Major themes from qualitative interviews included: importance of universal sleep-friendly cultures, environmental changes, and external incentives to improve patient sleep.

OBJECTIVE:To compare the frequency of stone-related events among patients receiving thiazides, alkali citrate, and allopurinol without prior 24-hour urine testing.  It is unknown whether one preventative pharmacological therapy (PPT) medication class is more beneficial for reducing kidney stone recurrence when prescribed empirically. MATERIALS AND METHODS/METHODS:Using medical claims data from working-age adults with kidney stone disease diagnoses (2008-2018), we identified those prescribed thiazides, alkali citrate, or allopurinol. We excluded those who received 24-hour urine testing prior to initiating PPT and those with less than three years of follow-up. We fit multivariable regression models to estimate the association between the occurrence of a stone-related event (emergency department visit, hospitalization, or surgery for stones) and PPT medication class. RESULTS:Our cohort consisted of 1,834 (60%), 654 (21%), and 558 (18%) patients empirically prescribed thiazides, alkali citrate, or allopurinol, respectively. After controlling for patient factors including medication adherence and concomitant conditions that increase recurrence risk, the adjusted rate of any stone event was lowest for the thiazide group (14.8%) compared to alkali citrate (20.4%) or allopurinol (20.4%) (each p<0.001). Thiazides, compared to allopurinol, were associated with 32% lower odds of a subsequent stone event by three years (OR 0.68, 95% CI 0.53-0.88). No such association was observed when comparing alkali citrate to allopurinol (OR 1.00, 95% CI 0.75-1.34). CONCLUSIONS:Empiric PPT with thiazides is associated with significantly lower odds of subsequent stone-related events. When 24-hour urine testing is unavailable, thiazides may be preferred over alkali citrate or allopurinol for empiric PPT.

Vocalizations are often elaborate, rhythmically structured behaviors. Vocal motor patterns require close coordination of neural circuits governing the muscles of the larynx, jaw, and respiratory system. In the elaborate vocalization of Alston's singing mouse (Scotinomys teguina) each note of its rapid, frequency-modulated trill is accompanied by equally rapid modulation of breath and gape. To elucidate the neural circuitry underlying this behavior, we introduced the polysynaptic retrograde neuronal tracer pseudorabies virus (PRV) into the cricothyroid and digastricus muscles, which control frequency modulation and jaw opening, respectively. Each virus singly labels ipsilateral motoneurons (nucleus ambiguus for cricothyroid, and motor trigeminal nucleus for digastricus). We find that the two isogenic viruses heavily and bilaterally colabel neurons in the gigantocellular reticular formation, a putative central pattern generator. The viruses also show strong colabeling in compartments of the midbrain including the ventrolateral periaqueductal gray and the parabrachial nucleus, two structures strongly implicated in vocalizations. In the forebrain, regions important to social cognition and energy balance both exhibit extensive colabeling. This includes the paraventricular and arcuate nuclei of the hypothalamus, the lateral hypothalamus, preoptic area, extended amygdala, central amygdala, and the bed nucleus of the stria terminalis. Finally, we find doubly labeled neurons in M1 motor cortex previously described as laryngeal, as well as in the prelimbic cortex, which indicate these cortical regions play a role in vocal production. The progress of both viruses is broadly consistent with vertebrate-general patterns of vocal circuitry, as well as with circuit models derived from primate literature.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:The aim of this study was to obtain a reliable estimate of single-sided deafness (SSD) prevalence in the adult U.S. POPULATION/METHODS/: METHODS:A cross-sectional national epidemiologic study was performed. Participants were included from the National Health and Nutrition Examination Survey (NHANES). Each cohort includes a nationally representative sample of approximately 5,000 noninstitutionalized civilians. Subjects 20 years old and over with audiometric testing were included. SSD was defined as normal hearing (pure-tone average [PTA] of ≤25 dB) in one ear and severe or worse hearing (PTA > 70 dB) in the other, using both three- and four-frequency PTA definition. Prevalence was measured as a raw number (n) and percentage (%) of the sample. Weighted estimates of prevalence were calculated based on the 2019 U.S. population census. RESULTS:An estimated 345,064 Americans (estimated prevalence of 0.14%, 95% confidence interval = 0.08-0.24) had SSD. SSD was more prevalent in individuals 60 to 79 years of age (estimated 155,917 U.S. adults, prevalence of 0.25%). A higher prevalence of SSD was noted among women compared to men (215,430 U.S. adult women, prevalence of 0.17% vs. 131,726 U.S. adult men, prevalence of 0.11%). Using a three-frequency PTA definition resulted in an estimated prevalence of 0.11%. Finally, 27% of adults with SSD reported having "good" or "excellent" hearing despite their hearing loss. CONCLUSIONS:The prevalence of SSD in the United States is estimated at 0.11%-0.14% (271,122 to 345,064 adults), depending on PTA definition used. These individuals could potentially benefit from auditory rehabilitation, including cochlear implantation. LEVEL OF EVIDENCE/METHODS:2 Laryngoscope, 2021.

The present study seeks to examine individuals' stream of thought in real time. Specifically, we asked participants to speak their thoughts freely out loud during a typical resting-state condition. We first examined the feasibility and reliability of the method and found that the oral reporting method did not significantly change the frequency or content characteristics of self-generated thoughts; moreover, its test-retest reliability was high. Based on methodological feasibility, we combined natural language processing (NLP) with the Bidirectional Encoder Representation from Transformers (BERT) model to directly quantify thought content. We analyzed the divergence of self-generated thought content and expressions of sadness and empirically verified the validity and behavioral significance of the metrics calculated by BERT. Furthermore, we found that reflection and brooding could be differentiated by detecting the divergence of self-generated thought content and expressions of sadness, thus deepening our understanding of rumination and depression and providing a way to distinguish adaptive from maladaptive rumination. Finally, this study provides a new framework to examine self-generated thoughts in a resting state with NLP, extending research on the continuous content of instant self-generated thoughts with applicability to resting-state functional brain imaging.

For the past half-century, cognitive and social scientists have struggled with the irrationalities of human choice behavior; people consistently make choices that are logically inconsistent. Is human choice behavior evolutionarily adaptive or is it an inefficient patchwork of competing mechanisms? In this review, I present an interdisciplinary synthesis arguing for a novel interpretation: choice is efficiently irrational. Connecting findings across disciplines suggests that observed choice behavior reflects a precise optimization of the trade-off between the costs of increasing the precision of the choice mechanism and the declining benefits that come as precision increases. Under these constraints, a rationally imprecise strategy emerges that works toward optimal efficiency rather than toward optimal rationality. This approach rationalizes many of the puzzling inconsistencies of human choice behavior, explaining why these inconsistencies arise as an optimizing solution in biological choosers.

OBJECTIVE:Preimplantation Genetic Testing - Aneuploidy (PGT-A) for embryo selection has undergone significant advancements in the last 2 decades and yet many studies still fail to demonstrate any clinical benefits over traditional embryo morphology selection (Mo-S). To understand this conundrum, we performed a multi-center clinical study of PGT-A patients, where Mo-S and euploid selection (Eu-S) outcomes were directly compared. METHOD:All suitable blastocysts were biopsied and analyzed for chromosome copy number. Outcomes (positive beta hCG, implantation, ongoing pregnancy, and live birth rates) for Eu-S were compared to Mo-S using single embryo transfers. RESULTS:Compared to Eu-S embryos, Mo-S embryos resulted in significant reduction of outcomes for positive beta hCG (p = 0.0005), implantation (p = 0.0008), ongoing pregnancy (p = 0.0046), livebirth (p = 0.0112), babies per transfer (p = 0.0112), and babies per embryo transferred (p = 0.0112). Morphology selection resulted in patients of all age groups having non-euploid embryos chosen for transfer. Post-hoc evaluation of individual clinic performances showed variable transfer outcomes that could potentially confound the true benefits of PGT-A. CONCLUSION:Embryo chromosome status is central to improved embryo transfer outcomes and sole reliance on current morphology-based selection practices, without Eu-S, will always compromise outcomes. Often overlooked but a major effector of successful PGT-A outcomes are individual clinic performances.

Dopamine (DA) is a critical regulator of striatal network activity and is essential for motor activation and reward-associated behaviors. Previous work has shown that DA is influenced by the reward value of food, as well as by hormonal factors implicated in the regulation of food intake and energy expenditure. Changes in striatal DA signaling also have been linked to aberrant eating patterns. Here we test the effect of leptin, an adipocyte-derived hormone involved in feeding and energy homeostasis regulation, on striatal DA release and uptake. Immunohistochemical evaluation identified leptin receptor expression throughout mouse striatum, including on striatal cholinergic interneurons and their extensive processes. Using fast-scan cyclic voltammetry, we found that leptin causes a concentration-dependent increase in evoked extracellular DA concentration ([DA]_o) in dorsal striatum and nucleus accumbens (NAc) core and shell in male mouse striatal slices, and also an increase in the rate of DA uptake. Further, we found that leptin increases cholinergic interneuron excitability, and that the enhancing effect of leptin on evoked [DA]_o is lost when nicotinic acetylcholine (ACh) receptors are antagonized or when examined in striatal slices from mice lacking ACh synthesis. Evaluation of signaling pathways underlying leptin's action revealed a requirement for intracellular Ca²⁺, and the involvement of different downstream pathways in dorsal striatum and NAc core versus NAc shell. These results provide the first evidence for dynamic regulation of DA release and uptake by leptin within brain motor and reward pathways, and highlight the involvement of cholinergic interneurons in this process.SIGNIFICANCE STATEMENTGiven the importance of striatal dopamine in reward, motivation, motor behavior and food intake, identifying the actions of metabolic hormones on dopamine release in striatal subregions should provide new insight into factors that influence dopamine-dependent motivated behaviors. We find that one of these hormones, leptin, boosts striatal dopamine release through a process involving striatal cholinergic interneurons and nicotinic acetylcholine receptors. Moreover, we find that the intracellular cascades downstream from leptin receptor activation underlying enhanced dopamine release differ among striatal subregions. Thus, we not only show that leptin regulates dopamine release, but also identify characteristics of this process that could be harnessed to alter pathological eating behaviors.