Faculty Bibliography

Neurodevelopmental disorders result from interactions between genetic predisposition and environmental risk factors, with infancy being the most vulnerable period. We designed a longitudinal study to determine how short-term antibiotic exposure during early postnatal life impacts the gut microbiome, neurodevelopment, and behavior, and whether these alterations were exacerbated by the neurodevelopmental disorder-associated 16p11.2 microdeletion (16pDel) mutation. The cephalosporin antibiotic, cefdinir, broadly altered the gut microbiome acutely, with persistent reductions in several Lachnospiraceae genera despite overall recovery. These alterations preceded long-term behavioral changes, including reduced juvenile sociability, compromised risk assessment, and deficits in associative learning. Remarkably, only cefdinir-exposed 16pDel mice had changes in hippocampal stem cell proliferation, subsequent adolescent cell numbers, and gene expression compared to other groups, demonstrating that genetic predisposition can modulate the effects of early-life antibiotic exposure on neurodevelopment. These alterations may be mediated by gastrointestinal disturbances, as cefdinir-exposed 16pDel males had increased intestinal permeability and shifted metabolite profiles including arginine biosynthesis and glycerophospholipid metabolism. Taken together, this study highlights how early-life microbial alterations affect behavior and reveals that genetic predisposition influences antibiotic-induced changes in hippocampal development. Further, these insights identify metabolic mechanisms as potential targets for intervention and may raise concerns regarding antibiotic use during infancy.

OBJECTIVES/OBJECTIVE:Home health care (HHC) plays a pivotal role in serving millions of US adults aging in place. Although the HHC population is growing rapidly in both size and diversity, driven by an aging US population and a changing demographic profile, there are increasing concerns of equity in HHC, particularly regarding how vulnerable populations are affected under current HHC practices. The purpose of this study was to examine the variations in accessing high-quality HHC in racial and ethnic minority groups and persons living with dementia. DESIGN/METHODS:Cross-sectional, secondary analysis. SETTING AND PARTICIPANTS/METHODS:Older adults who received HHC in 2016 from agencies with a star rating of overall care quality from the Home Health Compare program. METHODS:Start of care data from the 2016 HHC Outcome and Assessment Information Set was linked to Master Beneficiary Summary File, Home Health Compare, and Provider of Services file to address the aim. Multinomial regressions were used in analysis when risk-adjusting for individual and agency characteristics. RESULTS:Our risk-adjusted estimates, based on data from 574,682 older adults ≥65 years of age served by 8634 HHC agencies nationwide (2290 offering high-quality care, 4023 providing moderate-quality care, and 2321 delivering low-quality care), revealed significant disparities. Non-Hispanic Blacks (relative risk ratio, 0.62; 95% CI, 0.61-0.64) and Hispanics (relative risk ratio, 0.72; 95% CI, 0.70-0.74) were significantly less likely to receive care from high-quality agencies. Additionally, having dementia exacerbated disparities in accessing high-quality HHC between racial and ethnic minorities and White Americans. CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:Racial and ethnic minority individuals face significant disadvantages in accessing high-quality HHC, with persons living with dementia from these groups being the most disadvantaged. Further research is warranted to investigate the referral and admission processes for HHC. Our findings highlight the need for actions from clinicians and policymakers to tackle potential biases in the aforementioned care processes.

INTRODUCTION/UNASSIGNED:The intravoxel incoherent motion (IVIM) model of diffusion weighted imaging (DWI) provides imaging biomarkers for breast tumor characterization. It has been extensively applied for both diagnostic and prognostic goals in breast cancer, with increasing evidence supporting its clinical relevance. However, variable performance exists in literature owing to the heterogeneity in datasets and quantification methods. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:

Growing evidence suggests exposure to high temperatures may result in increased urban crime, a known driver of health and health inequity. Theoretical explanations have been developed to describe the heat-crime relationship without consensus yet achieved among experts. This scoping review aims to summarize evidence of heat-crime associations in U.S. cities. Further examination of empirical and translational inconsistencies in this literature will ensure future studies of urban heat-crime relationships in the U.S., and their policy impacts are informed by a thorough understanding of existing evidence. We performed a comprehensive literature search of empirical studies on heat-crime relationships in U.S. cities published between January 2000 and August 2023. The included studies were qualitatively synthesized based on operationalized exposures, outcomes, covariates, methodologies, theoretical framing, and policy implications. In total, 46 studies were included in this review. Most studies (93%) reported significant, positive associations between urban heat exposure and both violent and non-violent crime outcomes. The shape and strength of these associations varied based on operational definitions of urban heat exposures, crime outcomes, and relevant covariates in employed methods. We also found inconsistencies in the theoretical explanations and policy implications reported across studies. Climate-driven extreme heat events are projected to increase in frequency and severity. Our findings underscore the urgency of refining the understanding and translation of the complex relationship between urban heat and crime. In this review, we highlight opportunities to improve the methodological quality and responsible policy translation of future research in U.S. cities, which has implications for research globally.

The objective of this study was to establish recommendations for thromboprophylaxis in patients with endogenous Cushing's syndrome (CS), addressing the elevated risk of venous thromboembolism (VTE) associated with hypercortisolism. A Delphi method was used, consisting of 4 rounds of voting and subsequent discussions. The panel included 18 international experts from 11 countries and 4 continents. Consensus was defined as ≥75% agreement among participants. Recommendations were structured into the following categories: thromboprophylaxis, perioperative management, and VTE treatment. Consensus was reached on several critical areas, resulting in 14 recommendations. Key recommendations include: thromboprophylaxis should be considered at time of CS diagnosis and continued for 3 months after biochemical remission, provided there are no obvious contraindications. The standard weight-based prophylactic dose of low molecular-weight heparin is the preferred agent for thromboprophylaxis in patients with CS. Additionally, perioperatively and around inferior petrosal sinus sampling, thromboprophylaxis should be reconsidered if not already initiated at diagnosis. For VTE treatment, extended thromboprophylaxis is advised continuing for 3 months after Cushing is resolved. These Delphi consensus-based recommendations aim to standardize care practices and enhance patient outcomes in CS by providing guidance on thromboprophylaxis, including its initiation and continuation across various disease states, as well as the preferred agents to use. The panel also highlighted key areas for further research, particularly regarding the use of direct oral anticoagulants in CS and the management of mild CS and mild autonomous cortisol secretion. Additionally, the optimal duration of anticoagulant prophylaxis following curative treatment remains uncertain.

PURPOSE/OBJECTIVE:CAR T-cell therapy is an emerging anti-cancer therapeutic using modified T cells to attack a patient's cancer. The purpose of this study was to assess chest CT findings in patients undergoing CAR T-cell therapy to determine the most common CT manifestations. METHODS:We performed a retrospective test-retest study analyzing cases of patients who received CAR T-cell therapy who underwent chest CT prior to therapy and after therapy; a total of 349 patients were identified. CAR T-cell therapy was first administered in the mid 2010's, however we assessed for pre-treatment scans prior to this date. We reviewed patient's charts to collect demographic and clinical data. Two cardiothoracic radiologists reviewed chest CT scans prior to and post CAR T-cell therapy to determine new radiologic features post therapy. We analyzed which findings correlated with specific radiologic features on chest CT using student's t-tests or Chi squared tests. RESULTS:Pleural effusion was the most common CT manifestation resulting from CAR T-cell therapy, found in 26.3 % of patients. Patients with CT manifestations were more likely to present with dyspnea and cough (p = 0.000031 and p = 0.02, respectively). DISCUSSION/CONCLUSIONS:New symptoms in patients treated with CAR T-cell therapy may be an important harbinger of radiologic abnormalities. Clinicians should have a high index of suspicion for pleural effusions in patients presenting with symptoms who have undergone CAR T-cell therapy.

Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored. This review synthesizes current neuroscientific findings and introduces the dialectical-integration network (DIN) hypothesis, which identifies key brain regions such as the dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), dorsal lateral prefrontal cortex (DLPFC), nucleus accumbens, basal ganglia, and amygdala. These regions, along with networks like the default mode network (DMN) and frontoparietal network (FPN), facilitate holistic reasoning, conflict resolution, and sensory-emotional integration. The psychological benefits of dialectical thinking include enhanced cognitive flexibility, reduced emotional extremes, and improved conflict resolution. This review emphasizes the need for cross-cultural and neuroscientific research to explore the principle of change, a core aspect of dialectical cognition. By bridging cultural psychology and cognitive neuroscience, this work offers theoretical and methodological insights into culturally shaped cognitive styles, with practical applications in education, mental health, and intercultural communication. The DIN model provides a framework for future research on dynamic neural interactions supporting dialectical thinking.

OBJECTIVE/UNASSIGNED:This mixed methods study explores gender differences in, and reasons for, toothbrushing and flossing among Mexican-origin adults. METHODS/UNASSIGNED:Interviews and surveys about oral hygiene behaviors were collected from 72 adults (ages 21-40) living on the California-Mexico border. Interviews were audio-recorded, transcribed in their original language (English/Spanish), then coded. Survey responses were linked to coded transcripts in Dedoose. Qualitative reports were thematically analyzed for each behavior, stratified into four groups by gender and whether or not participants met American Dental Association (ADA) weekly guidelines (brushing ≥ 14/week; flossing ≥ 7/week). Self-reported weekly frequencies of brushing and flossing were collected continuously, and then dichotomized as meeting guidelines or not. Kruskal-Wallis and chi-square tests assessed differences in hygiene behavior frequency by gender. Negative binomial and logistic regressions were performed, accounting for socio-demographic characteristics. RESULTS/UNASSIGNED:= 0.0099) times the rate of weekly brushing than men in the full model; flossing frequency differences were not found. Men and women, whether ADA guidelines were met or not, identified similar brushing and flossing facilitators (health concerns, aesthetics), and barriers (lack of time, not being home). Some women (mothers) were motivated to brush to be role models for their children. Self-efficacy, or confidence in ability to brush or floss, was described differently by adults who met ADA guidelines (high self-efficacy) compared to the adults not meeting guidelines (low self-efficacy). CONCLUSIONS/UNASSIGNED:Integrating quantitative and qualitative data obtained from Mexican-origin adults identified few differences in both oral hygiene behaviors and the factors that influence their enactment.

STATEMENT OF THE CLINICAL PROBLEM ADDRESSED BY THE CASE/UNASSIGNED:We report an atypical clinical presentation of a rapidly progressive neurologic emergency that required prompt investigation and treatment of impending respiratory failure. We discuss the differential diagnosis, evaluation, emergency management, and treatment options of patients with atypical variants of this disorder. BRIEF DESCRIPTION OF CASE PRESENTATION/UNASSIGNED:A 56-year-old woman with a history of hypothyroidism, anxiety, and depression presented to the emergency department 3 weeks after an upper respiratory and ear infection with cough, pain with sinus palpation, tingling in her fingers bilaterally and right foot, hives, and an episode of blurry vision on awakening. She was discharged home with antibiotics. That evening, she developed rapidly progressing hoarseness and dysphagia and returned to the emergency department. An initial examination and laryngoscopy revealed complete left vocal cord paralysis, consistent with a left cranial nerve X palsy, which prompted a neurologic evaluation. Her examination progressively worsened over the next day requiring mechanical ventilation and ICU admission. SUMMARY OF THE KEY TEACHING POINT IN THE CASE/UNASSIGNED:New-onset bulbar cranial neuropathies should raise concern for neurologic disorders that can be rapidly progressive and result in respiratory failure. Urgent diagnosis and treatment are warranted.

BACKGROUND:No empirical data support the 54-58mm external diameter of intravaginal rings (rings) currently available and in development for contraception and other indications. Understanding how external diameter affects preference, adherence, and acceptability is critical for optimizing future product development. OBJECTIVES/OBJECTIVE:Our primary objectives were to determine which of three non-medicated rings of differing external diameters was preferred and yielded the highest adherence. Secondary objectives were comparing acceptability, patterns of adherence, and safety of the three rings. STUDY DESIGN/METHODS:In an open-label, three-way crossover trial, healthy, HIV-uninfected, monogamous, sexually active, non-pregnant,18-40-year-old cisgender women and their male partners in Atlanta, GA and the Bronx, NY were randomly assigned to the sequence of using three non-medicated silicone rings (46mm, 56mm, 66mm external diameters)continuously for approximately 30 days each (90 days total; November 2021-December 2022). We tested whether end of study preference for any of the three rings was greater than 0.33 (binomial proportion, exact test). We used mixed-effect regression models with random intercepts by participant to compare adherence (ring never out for longer than 30 minutes in 24 hours); and probability of removals (including reasons for removal), expulsions, and the ring being out of the vagina all day, per ring, per day of use with the 56mm ring as the reference group; and to compare scores on a novel 19-item acceptability scale with items related to ease and experience of use, and impact on sex. RESULTS:23/24 women completed the study (median age 26.7 years [SD 3.78]). Most were college graduates (92%), White (63%), non-Hispanic (79%), single (79%), and nulliparous (92%). At study end, 59% preferred the smallest (46mm) ring versus 18% each for the 56mm and 66mm rings (p=0.0045). The proportion of participants who were adherent did not differ significantly by ring (46mm, 78%; 56mm, 75%; 66mm, 59%; p=0.30), however, odds of expulsion were higher for the 46mm (OR 5.72, 95% CI: 1.25-26.1) and 66mm (OR 25.9, 95% CI: 6.11-109) rings than the 56mm ring. The 66mm ring also had greater odds of being out (removal or expulsion, any length of time) than the 56mm ring (OR 6.50, 95% CI 3.46-12.2). Mean acceptability scale scores were identical (4.54/5) for the 46mm and 56mm (smallest and medium) rings and significantly higher than the largest, 66mm ring (3.94/5; p<0.001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Although the 46mm ring was preferred by more women and had higher rates of adherence compared to the other two rings, the 56mm ring was rated as equally acceptable with significantly fewer reports of expulsions/removals compared to the other two rings. These data confirm that the current 54-58mm diameter of vaginal rings on the market and in development is acceptable and performs well. Future studies should explore the effect of other mechanical attributes, such as compressibility, on preference, adherence, and acceptability, as well as investigating ring characteristics in other populations.