Faculty Bibliography

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control of cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following the discovery that they predominantly function by inhibiting dendritic-targeting somatostatin (SST) expressing INs, thereby disinhibiting PCs. This VIP-SST disinhibitory circuit motif is observed throughout the neocortex from mice to humans, and serves as a key mechanism for top-down (feedback) and context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found to play an important role in sensory processing, control of executive functions, attention, sensorimotor integration and other cortico-cortical and thalamocortical feedback interactions. Furthermore, VIP INs have been implicated in mediating the effects of reinforcement signals, both reward and aversive, via their responsiveness to neuromodulators such as acetylcholine (ACh), and in facilitating synaptic plasticity and learning. While it is evident from transcriptomic analyses that VIP INs are a molecularly heterogeneous group, the physiological significance of this diversity is unclear at present. Here, we have characterized the functional diversity of VIP INs in the primary somatosensory cortex by leveraging intersectional genetic approaches to study distinct VIP IN subtypes. We found that VIP INs can be divided into four different populations: a group that expresses the Ca²⁺-binding protein calretinin (CR), two distinct groups that express the neuropeptide cholecystokinin (CCK), and a group that does not express either CR or CCK (non-CCK non-CR; or nCCK nCR). VIP neurons in each group exhibit different laminar distributions, axonal and dendritic arbors, intrinsic electrophysiological properties, and efferent connectivity, VIP/CR INs target almost exclusively SST INs, VIP/nCCK nCR INs also mainly target SST INs but also have connections to parvalbumin (PV) expressing INs. These two groups have essentially no connectivity to pyramidal cells (PCs). On the other hand, the two types of VIP/CCK INs target PCs, but differ in the degree to which synaptic release from each type is modulated by endocannabinoids. We also found that long-range inputs differentially recruit distinct VIP IN groups. Intriguingly, we find that distinct VIP IN populations target distinct SST INs subtypes in turn, indicating the presence of specialized VIP-SST disinhibitory subcircuits. Activation of distinct VIP IN subpopulations in vivo results in differential effects on the cortical network, thus providing evidence for modularity in VIP IN-mediated actions during cortical information processing.

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.

The substantial carbon footprint imparted by medical services warrants increased attention to their environmental impact. National guideline organizations such as the US Preventive Services Task Force (USPSTF) recommend multiple modalities for average-risk colorectal cancer (CRC) screening with varying resource intensity. The aim of this study was to quantify the environmental burden for 2 of the most used CRC screening modalities, colonoscopy and the multi-target stool DNA (mt-sDNA) test. A validated CRC microsimulation model was used to estimate the number of screening and follow-up tests for a cohort of 1 million average-risk individuals who underwent screening between ages 45 and 75. Component resources used for mt-sDNA, including waste products, energy, and transportation for colonoscopy and mt-sDNA, were collected from January 1, 2023, to January 1, 2024, and converted to carbon-equivalent emissions. Resources used for colonoscopy were captured from the literature. Resources devoted to screening colonoscopy were substantially (59%) higher than those to mt-sDNA, even when including follow-up colonoscopy. Of note, follow-up colonoscopy accounted for the majority (64%) of total emissions for the mt-sDNA screening strategy. Compared with colonoscopy screening, mt-sDNA substantially reduces the carbon emissions attributable to population-level CRC screening. Environmental impact should be included as a factor when choosing among guideline-recommended CRC screening strategies.

We present a series of network analyses aiming to uncover the symptom constellations of depression, anxiety and somatization among 2,796 adult primary health care attendees in Goa, India, a low- and middle-income country (LMIC). Depression and anxiety are the leading neuropsychiatric causes of disability. Yet, the diagnostic boundaries and the characteristics of their dynamically intertwined symptom constellations remain obscure, particularly in non-Western settings. Regularized partial correlation networks were estimated and the diagnostic boundaries were explored using community detection analysis. The global and local connectivity of network structures of public versus private healthcare settings and treatment responders versus nonresponders were compared with a permutation test. Overall, depressed mood, panic, fatigue, concentration problems and somatic symptoms were the most central. Leveraging the longitudinal nature of the data, our analyses revealed baseline networks did not differ across treatment responders and nonresponders. The results did not support distinct illness subclusters of the CMDs. For public healthcare settings, panic was the most central symptom, whereas in private, fatigue was the most central. Findings highlight varying mechanism of illness development across socioeconomic backgrounds, with potential implications for case identification and treatment. This is the first study directly comparing the symptom constellations of two socioeconomically different groups in an LMIC.

INTRODUCTION/BACKGROUND:Family history of cardiovascular disease (CVD) is an independent risk factor for coronary heart disease, and the risk increases with number of family members affected. It offers insights into shared genetic, environmental and lifestyle factors that influence heart disease risk. In this study, we aimed to estimate the association of family history of CVD and its risk factors, as well as the number of affected parents or siblings, with the prevalence of major cardiometabolic risk factors (CRFs) such as hypertension, dysglycemia, dyslipidemia and obesity in a sample of young adults. METHODS:The study utilized a cross-sectional analysis of baseline data from the UAE Healthy Future Study (UAEHFS), involving 5,058 respondents below the age of 40 years. Information on parental and sibling health regarding heart disease and stroke, hypertension, type 2 diabetes (T2D), high cholesterol and obesity, was gathered through a self-completed questionnaire. CRFs were estimated based on body measurements, biochemical markers and self-reported conditions. Multivariate regression analyses were used to examine the associations between categories of family history and the estimated CRFs. RESULTS:More than half (58%) of the sample reported having a positive family history of CVD or its risk factors. The most common family history reported was T2D and hypertension, which accounted for 39.8% and 35% of the sample, respectively. The prevalence of all CRFs was significantly higher among those with a positive family history compared to those without family-history (P < 0.001). The prevalence and likelihood of having a CRF increased as the number of parents and/or siblings affected increased, indicating a potential dose-response trend. The odds were highest among individuals with both parental-and-sibling family history of disease, where they increased to 2.36 (95% CI 1.68-3.32) for hypertension, 2.59 (95% CI 1.86-3.60) for dysglycemia, 1.9 (95% CI 1.29-2.91) for dyslipidemia and 3.79 (95% CI 2.83-5.06) for obesity. CONCLUSION/CONCLUSIONS:In this study, we addressed the effect of family history as an independent risk factor on the major CRFs for the first time in the region. We observed that the majority of young Emirati adults had a positive family history of CVD-related diseases. Family history showed a strong association with the increased prevalence of CRFs. Additionally, having more relatives with specific diseases was associated with a higher risk of developing CRFs. Identifying people with a history of these conditions can help in early intervention and personalized risk assessments.

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.

Solid organ transplantation (SOT) offers people with end-stage organ disease an increased quality of life, which includes the return of fertility and the potential for pregnancy. Although the number of pregnancies has increased, definitive recommendations have been lacking. To address reproductive health in SOT recipients, the American Society of Transplantation Women's Health Community of Practice held a virtual Controversies Conference with subject matter experts gathered to discuss topics of contraception, immunosuppression, and pregnancy in SOT recipients and pregnancy post-living donation. This publication is a synthesis of expert guidance and available data regarding pregnancy management and outcomes after all types of SOTs.

The objective of this study is to evaluate an intervention designed to reduce human trafficking among Denotified Tribes (DNTs) in two regions of India. We will conduct a cluster-randomized controlled trial utilizing a participatory-designed, community health worker (CHW)- delivered public health intervention. CHWs will be trained to conduct anti-human-trafficking advocacy and psychological first aid (humane, supportive and practical assistance to people who are distressed) to DNT community members, and mobilize resources to ensure access to health and mental health services, education, livelihoods, and government benefits. This project leverages known effective, systemic, and sustainable approaches to reducing vulnerabilities to trafficking among DNT communities, through increased economic alternatives, health and mental health services guided by the trafficking-survivor-informed treatment protocols.

The rising global incidence of breast cancer and the persistent shortage of specialized radiologists have heightened the demand for innovative solutions in mammography screening. Artificial intelligence (AI) has emerged as a promising tool to bridge this demand-supply gap, with potential applications ranging from full automation to integrated AI-human decision-making. This study evaluates the economic feasibility of incorporating artificial intelligence (AI) into mammography screening within healthcare settings, considering full or partial integration. To evaluate the economic viability, we employ an optimization model specifically designed to minimize mammography screening costs. This model considers three distinct approaches when interpreting mammograms: automation strategy utilizing AI exclusively, delegation strategy involving the selective allocation of tasks between radiologists and AI, and the expert-alone strategy relying solely on radiologist decisions. Our findings underscore the significance of disease prevalence in relation to the trade-off between costs associated with false positives (e.g., follow-up expenses) and false negatives (e.g., litigation costs stemming from missed diagnoses) in shaping the AI strategy for healthcare organizations. We backtest our approach using data from an AI contest in which participants aimed to match or surpass radiologists' performance in assessing screening mammograms for women. The contest data supports the optimality of the delegation strategy, potentially leading to cost savings of 17.5% to 30.1% compared to relying solely on human experts. Our research provides guidance for healthcare organizations considering AI integration in mammography screening, with broader implications for work design and human-AI hybrid solutions in various fields.

The prevalence of vitamin D deficiency among intensive care unit (ICU) patients is potentially associated with an increased risk of mechanical ventilation, sepsis, prolonged hospital stays, and mortality. Although ICU patient care has significantly improved in recent years, the role of vitamin D supplementation remains under investigation. A literature review was conducted using PubMed, Web of Science, Embase, and Cochrane databases, focusing on randomized controlled trials published in the past five years on vitamin D supplementation in adult ICU patients. Patients' baseline vitamin D levels, administration routes, doses, biomarker changes, mechanical ventilation duration, length of hospital stay, and mortality were analyzed. Although vitamin D supplementation appears safe and may reduce ICU stay duration and mechanical ventilation time and improve SOFA scores, its impact on overall mortality remains uncertain. Routine supplementation for all ICU patients is not currently recommended; clinical decisions should consider individual baseline vitamin D levels, patient characteristics, severity of illness, doses, and administration methods.