Faculty Bibliography

BACKGROUND:As individuals age, the immune system undergoes complex changes, including an increase in the number of CD8 T cells relative to CD4 T cells, a decline in naïve cell production (including T and B cells), and an accumulation of terminally differentiated cells with diminished functionality. These age-related immune alterations collectively contribute to immunosenescence, a phenotype associated with aging-related declines and diseases such as dementia, Alzheimer's disease, osteoporosis, and diabetes. Premature mortality at older ages often results from cumulative health deterioration initiated by physiological dysregulation over the life course. Mortality risk, therefore, provides a meaningful measure of the long-term impact of physiological changes, including those related to the immune system. Examining the link between mortality risk and immune aging in older adults could illuminate the underlying pathology of aging-related health decline. This study uses data from the Health and Retirement Study (HRS), a national, population-based sample of middle-aged and older Americans, to explore the relationship between specific immune aging ratios and six-year mortality, stratified by race/ethnicity and sex. RESULTS:Using a sample of 8,259 individuals from the HRS, we found that overall, the presence, magnitude, and direction of the association differed by the specific immune ratio measure, sex, and race/ethnicity. We found particularly robust associations among Hispanic and non-Hispanic Black females. Among Hispanic females, for example, a one-unit increase in the log CD4 EMRA: Naïve ratio was associated with a nearly 50% increase in mortality for Hispanic females and a 25% increase in mortality for non-Hispanic Black females which was robust to adjustment for additional covariates. While we found little evidence of an association between immune function and mortality among non-Hispanic White and Hispanic males, we found associations in the opposite direction as what we would expect among non-Hispanic Black males. For example, a one-unit increase in the CD4, EMRA: Naïve ratio was associated with a 15% decrease in mortality among non-Hispanic Black males. CONCLUSIONS:Our findings demonstrate that associations between immune aging and mortality are not uniform but instead vary in magnitude and direction across sex and racial/ethnic subgroups. The strongest and most consistent associations were observed among Hispanic and non-Hispanic Black females-groups experiencing multiple forms of marginalization-suggesting that these populations may face heightened vulnerability to the downstream consequences of immune aging. However, the absence or reversal of expected associations in some subgroups-particularly non-Hispanic Black males-underscores the complexity of immune aging processes and their interaction with social and biological contexts. These results highlight the importance of disaggregated analyses and suggest that immune aging may manifest and impact mortality risk differently across populations.

BACKGROUND:The design and integration of technology within inpatient hospital rooms has a critical role in supporting nursing workflows, enhancing provider experience, and improving patient care. As health care technology evolves, there is a need to design "future-proofed" physical environments that integrate technology in ways that support workflows and maintain clinical performance. Assessing how current technologies affect nursing workflows can help inform the development of these future environments. OBJECTIVE:We assessed the current challenges nursing staff face in inpatient rooms, gather insights on technology, and build environment interactions to envision the design of a technology-integrated "Inpatient Room of the Future." METHODS:A qualitative study was conducted involving semistructured interviews, shadowing, and focus groups among nursing staff in the inpatient setting. Methods including horizon scanning, scenario analysis, technology assessment, and backcasting facilitated a comprehensive qualitative analysis of current technology use and needs in inpatient nursing workflows to inform exploratory design considerations for technology-integrated envisioned futures solutions. RESULTS:In total, 26 nursing staff across 4 inpatient hospital units participated in this study. Analysis identified four major themes considered central to designing a technology-integrated inpatient room that enhances nursing workflow and experience: (1) the need for seamless integration of technologies advocating for a unified system that minimizes fragmented technology use and enhances efficiency; (2) the potential for technology to reduce cognitive load, alleviate mental strain, and streamline complex workflows; (3) a focus on enhancing interpersonal communication with specific emphasis on tools that facilitate clear and efficient communication among clinicians and with patients; and (4) the importance of improved staff well-being with design considerations aimed at promoting both physical and mental health for health care workers in the inpatient setting. Envisioned future solutions included enhanced patient monitoring with automated measurements and actions through computer vision and data triangulation, a smart electronic health record-integrated supply management system using computer vision to detect supply shortages and auto-delivery of needed supplies, and a personal tech smart assistant capable of real-time patient monitoring and escalation, task prioritization, and hands-free clinical documentation and communication. CONCLUSIONS:While current technologies address specific tasks, there are significant opportunities for better technology integration, reducing cognitive load, enhancing communication, and promoting the physical and mental well-being of nursing staff. Future research should focus on seamless technology integration aligned with clinical workflows and implementing supportive technologies that do not interfere with clinician judgment and critical thinking. Policy recommendations include oversight mechanisms for evaluating artificial intelligence-enabled devices, safeguarding patient information, and ensuring nurses are actively involved at every stage of technology development and implementation. Future inpatient unit designs should actively engage input from both nursing professionals and technologists in developing future-proofed clinical spaces to ensure the creation of integrated systems that foster a cohesive and harmonious user experience.

Altered fetal brain function is proposed as a mechanism underlying the relationship between prenatal maternal depression (PMD) and neurodevelopmental outcomes in offspring. This study investigated the association between PMD symptoms and fetal brain functional connectivity (FC) using graph theory. A total of 123 pregnant women participated in the study, completed the Center for Epidemiologic Studies Depression Scale (CES-D), and underwent fetal MRI scans. Results revealed a significant relationship between elevated PMD symptoms and reduced global efficiency in the right insular region of the fetal brain. However, because fetal age was not associated with local or global efficiency in the insular brain region, we cannot determine if the PMD-related reduction in insula global efficiency is indicative of an accelerated or delayed developmental pattern. This study is one of the few to examine fetal brain connectivity in relation to prenatal maternal depression, providing valuable insights into early neurodevelopmental risks and potential targets for early intervention.

OBJECTIVE:This study examined racial and ethnic differences in percent total weight loss (%TWL) and glycemic improvement following sleeve gastrectomy (SG) and explored the role of socioeconomic and psychosocial factors in postsurgical outcomes. METHODS:This longitudinal study included patients who underwent SG between 2017 and 2020, with follow-up visits over 24 months. RESULTS:Non-Hispanic Black (NHB) participants had lower %TWL at 3, 12, and 24 months compared with Hispanic (H) and non-Hispanic White (NHW) participants. Fat mass index was initially lower in NHB, with smaller reductions over time and significant group differences persisting at 24 months. NHB participants had higher baseline fat-free mass index values; by 24 months, fat-free mass index values were lower in H participants. Hemoglobin A1c decreased across all groups but remained consistently higher in NHB and H compared with NHW at 24 months. NHB participants reported higher perceived discrimination, sleep disturbance, and perceived stress than H and NHW participants at all time points. Employment status predicted %TWL at 12 months. There was a significant interaction between race and ethnicity and employment status observed at 12 and 24 months, suggesting that employment-related disparities could impact surgical outcomes. CONCLUSIONS:NHB participants experienced less favorable outcomes following SG, emphasizing the need for tailored interventions addressing socioeconomic and psychosocial disparities.

BACKGROUND:Maternal infections are linked to neurodevelopmental impairments, highlighting the need to investigate SARS-CoV-2-induced immune activation. OBJECTIVE:This study aimed to evaluate the impact of maternal infection on neurodevelopment and investigate whether cytokine and chemokine profiles predict delays at 24 months. METHODS:Conducted in Brazil (January 2021-March 2022), this follow-up study included 18 SARS-CoV-2 positive pregnant women at 35-37 weeks' gestation, 15 umbilical cord blood samples, and blood samples from 15 children at 6 months and 14 at 24 months. Developmental delay was defined using the Bayley Scales of Infant and Toddler Development, Third Edition, with scores below 90 in cognitive, communication, or motor domains. RESULTS:At 6 months, 33.3% of infants exhibited cognitive delays, 20% communication delays, and 40% motor delays, increasing to 35.71%, 64.29%, and 57.14% at 24 months, respectively. Elevated interferon-gamma and tumor necrosis factor-alpha in cord blood correlated with cognitive delays, while interleukin (IL)-6, IL-8, IL-17, and IL-1β were associated with motor delays. Increased C-X-C motif chemokine ligand 10 and other cytokines were associated with communication delays. CONCLUSION/CONCLUSIONS:Maternal SARS-CoV-2 may impact infant neurodevelopment, as early cytokine elevations correlate with delays, highlighting the importance of early monitoring and interventions to reduce long-term effects. IMPACT/CONCLUSIONS:Prenatal SARS-COV-2 infection in pregnant women is linked to developmental delays in toddlers, with cytokine and chemokine changes associated with neurodevelopmental outcomes at 24 months. This study shows the long-term impact of maternal SARS-COV-2 infection on child development, highlighting inflammatory markers like IFN-γ, TNFα, IL-6, IL-8, IL-17, IL-1β, and CXCL10. Identifying specific cytokines correlating with cognitive, communication, and motor delays suggests potential biomarkers for early intervention. Conducted in Fortaleza, Brazil, the study emphasizes understanding local epidemiological impacts on child development, especially in regions with high infection rates. Graphical depiction of the SARS-CoV-2-induced maternal immune activation and its impact on the child's neurological development. Maternal immune activation from SARS-CoV-2 infection can affect a baby's neurological development, leading to motor, communication, and cognitive delays, assessed at 6 and 24 months old. Alterations in cytokine and chemokine levels in cord blood at six months may help predict these adverse outcomes observed at 24 months.

BACKGROUND/UNASSIGNED:The relationship between prenatal exposure to low-level air pollution and child autism spectrum disorder (ASD) is unclear. OBJECTIVE/UNASSIGNED:To examine associations of prenatal air pollution exposure with autism. METHODS/UNASSIGNED:quantiles) using quantile regression and with ASD diagnosis using logistic regression. Models were run within census divisions, and coefficients were pooled in a meta-analysis. RESULTS/UNASSIGNED:also was associated with ASD. DISCUSSION/UNASSIGNED:Associations with ASD outcomes were present even at low levels of air pollutants. https://doi.org/10.1289/EHP16675.

BACKGROUND/UNASSIGNED:Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child neurodevelopment during pregnancy. OBJECTIVE/UNASSIGNED:We investigated whether OPE urinary concentrations during pregnancy were associated with child autism-related outcomes. METHODS/UNASSIGNED:We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [> median], moderate [≤ median], non-detect), or as detect/non-detect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS/UNASSIGNED:Compared with non-detectable concentrations, high exposure to bis(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs. non-detect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs. non-detect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION/UNASSIGNED:Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with higher risk of autism diagnosis and related traits in childhood. https://doi.org/10.1289/EHP16177.

Effective mild cognitive impairment (MCI) screening requires accessible testing. This study compared two tests for distinguishing MCI patients from controls: Rapid Automatized Naming (RAN) for naming speed and Low Contrast Letter Acuity (LCLA) for sensitivity to low contrast letters. Two RAN tasks were used: the Mobile Universal Lexicon Evaluation System (MULES, picture naming) and Staggered Uneven Number test (SUN, number naming). Both RAN tasks were administered on a tablet and in a paper/pencil format. The tablet format was administered using the Mobile Integrated Cognitive Kit (MICK) application. LCLA was tested at 2.5% and 1.25% contrast. Sixty-four participants (31 MCI, 34 controls; mean age 73.2 ± 6.8 years) were included. MCI patients were slower than controls for paper/pencil (75.0 vs. 53.6 sec, p < 0.001), and tablet MULES (69.0 sec vs. 50.2 sec, p = 0.01). The paper/pencil SUN showed no significant difference (MCI: 59.5 sec vs. controls: 59.9 sec, p = 0.07), nor did tablet SUN (MCI: 59.3 sec vs. controls: 55.7 sec, p = 0.36). MCI patients had worse performance on LCLA testing at 2.5% contrast (33 letters vs. 36, p = 0.04*) and 1.25% (0 letters vs. 14. letters, p < 0.001). Receiver operating characteristic (ROC) analysis showed similar performance of paper/pencil and tablet MULES in distinguishing MCI from controls (AUC = 0.77), outperforming both SUN (AUC = 0.63 paper, 0.59 tablet) and LCLA (2.5% contrast: AUC = 0.65, 1.25% contrast: AUC = 0.72). The MULES, in both formats, may be a valuable screening tool for MCI.

PurposeTo evaluate the association between demographic characteristics and weight-loss in response to financial incentives designed using behavioral economics.DesignRetrospective analysis of randomized clinical trial (RCT).SettingFIReWoRk RCT (NCT03157713), which found that financial incentives were more effective than provision of weight-management resources only for weight-loss.Subjects668 adults with obesity (221 in resources-only group, 447 in incentive groups) living in low-income neighborhoods.MeasuresDemographic characteristics and weight-loss.AnalysisLinear mixed-effects models with interaction terms to examine effect of incentives on weight-loss in different demographic groups.ResultsMean age of participants was 47.69 years, 81.0% were women, 72.6% were Hispanic, and mean BMI was 37.95 kg/m². Financial incentives increased percent weight loss at 6 months (difference in percent weight loss between financial incentive and resources-only group = -2.41%; 95% CI -3.23% to -1.58%). In fully adjusted models, participants who were Black lost less weight than participants who were White (difference in percent weight loss = 2.12%; 95% CI 0.25% to 3.99%). Differences in percent weight loss by sex, age, education and neighborhood income were absent. Models that tested for interactions between group assignment and percent weight loss did not demonstrate evidence of a heterogenous effect of incentives in sociodemographic subgroups.ConclusionBlack participants in the FIReWoRk intervention lost less weight than White participants, but effectiveness of financial incentives generally did not vary significantly by sociodemographic characteristics. However, it remains important to evaluate potential impacts of financial incentive programs on health disparities.