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Immigrant Inequities in Uninsurance and Postpartum Medicaid Extension: A Quasi-Experimental Study in New York City, 2016–2021Objectives. To determine if de facto postpartum Medicaid extension during the Families First Coronavirus Response Act (FFCRA) reduced immigrant versus US-born inequities in uninsurance. Methods. We assessed self-reported uninsurance at 2 to 6 months postpartum among people with Medicaid-paid births using the New York City Pregnancy Risk Assessment Monitoring System (PRAMS), comparing immigrant and US-born people. We created a pre-FFCRA cohort of 2611 births from 2016 to 2019 and a post-FFCRA implementation cohort of 1197 births from 2020 to 2021. We calculated risk differences using log binomial regression. Results. Self-reported postpartum uninsurance among immigrants decreased from 13.6% to 9.3% after FFCRA (adjusted risk difference = -4.9%; 95% confidence interval = -7.8%, -2.0%). Immigrant versus US-born inequities in postpartum uninsurance decreased except among Hispanic birthing people, among whom 1 in 6 reported they were uninsured during FFCRA, despite continued eligibility. Conclusions. De facto postpartum Medicaid extension decreased immigrant inequities in insurance coverage, but Hispanic immigrants may have been unaware of continued coverage. Public Health Implications. Postpartum Medicaid extension policies that are inclusive of all immigrants may decrease inequities, but community-integrated implementation is needed to raise awareness of coverage and advance postpartum maternal health equity.
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Maternal Group B Streptococcus Infection Correlates Inversely With Preeclampsia in Pregnant African American WomenObjective: To determine whether an association exists between group B Streptococcus (GBS) colonization and preeclampsia among pregnant Black women. Methods: This retrospective cross-sectional study involved Black women who gave birth at State University of New York Downstate Hospital between January 2010 and December 2017. Data were collected from the Obstetric Department, including delivery date, time, mode of delivery, age of the mother, weeks of gestation at delivery, and antepartum complications. The GBS test results were originally determined using the eSwab transport system. Preeclampsia was defined based on the American College of Obstetricians and Gynecologists criteria for the periods 2010-2012 and 2013-2017. The primary outcome was whether GBS was associated with the outcome of preeclampsia in the population of Black women. Covariates, including smoking status, gestational age, parity, body mass index, maternal age, and presence of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) were examined as potential confounders. Chi-squared test and logistic regression model were used, presenting odds ratios with 95% confidence intervals (P < 0.050), analyzed with SAS on Demand for Academics (SAS Institute, Inc., NY). Results: Among the 8,019 Black women included in this study, GBS-positive women (n = 977) had a 53% reduction in the likelihood of being diagnosed with preeclampsia compared to GBS-negative women (adjusted odds ratio, 0.47; 95% confidence interval, 0.32-0.70). We did not find evidence of differences in the distribution of smoking habits (P = 0.783) or maternal age (P = 0.107) between GBS-positive and GBS-negative women. However, the GBS-positive women tended to be less likely to have a preterm delivery (9.62% (94/977) vs. 24.24% (1707/7042), P < 0.001), less likely to be nulliparous (33.37% (326/977) vs. 37.87% (2667/7042), P = 0.006), and less likely to be obese (51.38% (502/977) vs. 55.30% (3894/7042), P < 0.001) compared with GBS-negative women. In contrast, GBS-positive women were more likely to have a comorbid infection than their counterparts: HSV (5.94% (58/977) vs. 2.63% (185/7042), P < 0.001) and HIV (1.54% (15/977) vs. 0.82% (58/7042), P = 0.028). Conclusion: We found a reduced likelihood of preeclampsia among women who were positive for GBS at delivery. Given the cross-sectional nature of our study, more research is needed to further explore this association.
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Social Media and Black Maternal Health: The Role of Health Literacy and eHealth LiteracyBackground: Black women experience greater maternal mortality and morbidity than White women. Although there are many causes of this disparity, providing more and better maternal health information to this population may be beneficial. Social media offers a way to easily and quickly disseminate information to empower and educate Black women about health during pregnancy. Objective: This study sought to identify social media use patterns to determine what sources Black women used to obtain information about pregnancy and to explore whether health literacy/eHealth literacy influence those patterns. Methods: This cross-sectional, nationally representative survey panel included 404 Black women. Health literacy was measured by the Single Item Literacy Screener, and eHEALS was used to measure eHealth literacy. We examined participants' social media activity, social media use, social media use for support, and sharing of pregnancy-related health information. Relationships between health literacy, eHealth literacy, and social media use were assessed. Key results: Overall, 67.5% of participants had high health literacy, and the average eHealth literacy score was high (34.5). Most women (71.6%) reported using more than three social media accounts as a source for pregnancy information. Women with low health literacy searched social media for general and specific pregnancy health information, reported more social media use during pregnancy in general (p < .001), and more use of social media for giving and getting support (p = .003). Women with higher eHealth literacy were more likely to report more social media use (r = 0.107, p = .039) and often used social media to give and get support (r = 0.197, p = .0001). Women with high health literacy more often reported sharing the pregnancy information they found on social media with their nurse (χ2 = 7.068, p = .029), doula (χ2 = 6.878, p = .032), and childbirth educator (χ2 = 10.289, p = .006). Women who reported higher eHealth literacy also reported more often sharing the pregnancy information they found on social media with their doctor (r = 0.115, p = .030), nurse (r = 0.139, p = .001), coworkers (r = 0.160, p = .004), and family or friends (r = 0.201, p = .0001). Conclusion: Substantial numbers of Black women use social media to find pregnancy health information. Future studies should elicit more detailed information on why and how Black women use social media to obtain pregnancy information and support as well as what role health literacy and eHealth literacy may have on birth outcomes. [HLRP: Health Literacy Research and Practice. 2023;7(3):e119-e129.].
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Utilization of Maternal Health Care Among Immigrant Mothers in New York City, 2016–2018Immigrant women represent half of New York City (NYC) births, and some immigrant groups have elevated risk for poor maternal health outcomes. Disparities in health care utilization across the maternity care spectrum may contribute to differential maternal health outcomes. Data on immigrant maternal health utilization are under-explored in the literature. We conducted a cross-sectional analysis of the population-based NYC Pregnancy Risk Assessment Monitoring System survey, using 2016-2018 data linked to birth certificate variables, to explore self-reported utilization of preconception, prenatal, and postpartum health care and potential explanatory pathways. We stratified results by maternal nativity and, for immigrants, by years living in the US; geographic region of origin; and country of origin income grouping. Among immigrant women, 43% did not visit a health care provider in the year before pregnancy, compared to 27% of US-born women (risk difference [RD] = 0.16, 95% CI [0.13, 0.20]), 64% had no dental cleaning during pregnancy compared to 49% of US-born women (RD = 0.15, 95% CI [0.11, 0.18]), and 11% lost health insurance postpartum compared to 1% of US-born women (RD = 0.10, 95% CI [0.08, 0.11]). The largest disparities were among recent arrivals to the US and immigrants from countries in Central America, South America, South Asia, and sub-Saharan Africa. Utilization differences were partially explained by insurance type, paternal nativity, maternal education, and race and ethnicity. Disparities may be reduced by collaborating with community-based organizations in immigrant communities on strategies to improve utilization and by expanding health care access and eligibility for public health insurance coverage before and after pregnancy.
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Association between triclosan levels and white blood cell counts in US adults from NHANES, 2011–2012Triclosan is a broad-spectrum antimicrobial agent used in a multitude of healthcare and consumer products. Epidemiological studies link triclosan exposure to several adverse health outcomes including alterations in thyroid function and an increased risk for allergies and asthma suggesting an immunomodulatory role for the endocrine disrupting synthetic chemical. The effects of triclosan on the human immune system, particularly on the levels and function of white blood cells, have yet to be fully characterized. Using cross-sectional data from the NHANES 2011–2012 survey, we examined the relationship between triclosan exposure levels and white blood cell counts in adults 18–65 years of age. Results from multivariable linear regression analysis show lack of a statistically signficant association between urinary triclosan levels and white blood cell counts (β = −0.0007, p = 0.90, 95% CI = −0.012, 0.010). Findings may demonstrate an absence of association or may indicate that triclosan exposure levels were too low to have a significant detectable impact on white blood cell counts. Considering that prior animal and epidemiological studies have established links between triclosan exposure and alterations in immune system parameters and susceptibility to allergic diseases, the effects of triclosan exposure on the immune system should continue to be evaluated.
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Association between Urinary Triclosan and Serum Testosterone Levels in U.S. Adult Males from NHANES, 2011–2012Triclosan was introduced into the market in the 1970s and has since been used as an antimicrobial agent in a diverse array of consumer and personal care products. Although it has been widely used over a number of years, there is growing concern and debate over its safety and efficacy and its potential as an endocrine disruptor. Although prior animal toxicology studies have shown an association between triclosan and decreased testosterone levels, human studies have been limited, particularly for adult men. Using the National Health and Nutrition Examination Survey data (NHANES, 2011–2012), we examined the association of urinary triclosan on testosterone levels in adult men 18–65 years of age. Multivariable linear regression analysis failed to show an association between triclosan and serum testosterone (β = 0.0003, p = 0.98, 95% CI = −0.024, 0.025). The results suggest there is no association or that triclosan concentrations are too low to cause a significant impact on testosterone levels. Additionally, longitudinal studies would provide a more comprehensive understanding of the direction of change and magnitude of causal relationships over time.
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The National Children’s Study: Recruitment Outcomes Using the Provider-Based Recruitment ApproachObjective: In 2009, the National Children's Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment. Methods: The NCS aimed to recruit 18- to 49-year-old women who were pregnant or at risk for becoming pregnant who lived in designated geographic segments within primary sampling units, generally counties. Using provider-based recruitment, 10 study centers engaged providers to enroll eligible participants at their practice. Recruitment models used different levels of provider engagement (full, intermediate, information-only). Results: The percentage of eligible women per county ranged from 1.5% to 57.3%. Across the centers, 3371 potential participants were approached for screening, 3459 (92%) were screened and 1479 were eligible (43%). Of those 1181 (80.0%) gave consent and 1008 (94%) were retained until delivery. Recruited participants were generally representative of the county population. Conclusions: Provider-based recruitment was successful in recruiting NCS participants. Challenges included time-intensity of engaging the clinical practices, differential willingness of providers to participate, and necessary reliance on providers for participant identification. The vast majority of practices cooperated to some degree. Recruitment from obstetric practices is an effective means of obtaining a representative sample.
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CLOSED-LOOP CONNECTIVITY BEST SUPPORTS INFORMATION PROCESSING AND SLEEP DYNAMICS IN THE MOUSE THALAMO-CORTICAL WHISKER PATHWAY: A COMPUTATIONAL STUDYDespite recent advancements in mapping thalamic and cortical projections, the specific organization of intrathalamic connectivity remains elusive. Current experimental approaches cannot definitively determine whether these connections are arranged in reciprocal (closed-) or non-reciprocal (open-loop) circuits. Understanding the organization of intrathalamic projections could fundamentally reshape our view of thalamic processing. Closed-loop circuits may promote localized and recurrent processing, whereas open-loop circuits may facilitate broader integration of signals across thalamic regions. Computational modeling provides an alternative for probing the functional consequences of different intrathalamic architectures, circumventing experimental limitations. With this in mind, we developed a biophysically detailed multi-compartmental model of the mouse whisker pathway, built on anatomical and physiological data. Our goal was to determine whether closed- or open-loop connectivity can best reproduce key characteristics of cell and network responses in the mouse whisker pathway across wakefulness and sleep. We showed that closed-loop connectivity between the thalamocortical (TC) relay neurons in the ventral posteromedial nucleus and the inhibitory interneurons in the thalamic reticular nucleus (TRN) best reproduces thalamic spiking and local field potential responses across awake and sleep states. In this model, feedforward (TC→TRN) on-center projections (i.e., spatially aligned) regulate the angular tuning in the awake state, while on-center feedback (TRN→TC) supports spindle oscillations during sleep. We also showed that direct activation of closed-loop corticothalamic feedback (CT→TC and CT→TRN) by TC inputs can sharpen the angular tuning in the thalamus. These results underscore the importance of closed-loop connectivity in unifying wake and sleep dynamics, offering insights into how thalamo-cortical circuits balance precise sensory tuning with robust oscillatory rhythms across behavioral states.
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Addressing structural mentoring barriers in postdoctoral training: a qualitative studyPurpose –: Structural mentoring barriers are policies, practices and cultural norms that collectively disadvantage marginalized groups and perpetuate disparities in mentoring. This study aims to better understand structural mentoring barriers at the postdoctoral training stage, which has a direct impact on faculty diversity and national efforts to retain underrepresented groups in research careers. Design/methodology/approach –: A diverse sample of postdoctoral scholars ("postdocs") from across the USA were asked to participate in focus groups to discuss their training experiences. The authors conducted five 90-min focus groups with 32 biomedical postdocs, including 20 (63%) women and 15 (47%) individuals from underrepresented racial/ethnic groups (URG). Findings –: A social-ecological framework was used to categorize both the upstream and downstream manifestations of structural mentoring barriers, as well as mentoring barriers, overall. Notable structural barriers included: academic politics and scientific hierarchy; inequalities resulting from mentor prestige; the (over) reliance on one mentor; the lack of formal training for academic and non-academic careers; and the lack of institutional diversity and institutional mentor training. To overcome these barriers, postdocs strongly encouraged developing a network or team of mentors and recommended institutional interventions that create more comprehensive professional development, mentorship and belonging. Originality/value –: For postdoctoral scientists, structural mentoring barriers can permeate down to institutional, interpersonal and individual levels, impeding a successful transition to an independent research career. This work provides strong evidence for promoting mentorship networks and cultivating a "mentoring milieu" that fosters a supportive community and a strong culture of mentorship at all levels.
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Inconsistencies in the published rabbit ribosomal rRNAs: a proposal for uniformity in sequence and site numberingExamination of all publicly available Oryctolagus cuniculus (rabbit) ribosome cryo-EM structures reveals numerous confusing inconsistencies. First, there are a plethora of single-nucleotide differences among the various rabbit 28S and 18S rRNA structures. Second, two nucleotides are absent from the NCBI Reference Sequence for the 18S rRNA gene. Moving forward, we propose using the Broad Institute's rabbit whole-genome shotgun sequence and numbering to reduce modeling ambiguity and improve consistency between ribosome models.
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Access to Interpretable Data to Support Disproportionate Health Risks from Industrial Releases: A Case Study on the Environmental Protection Agency’s Datasets and Their Application to the Latinx Communities of Houston, TexasLatinx communities face disproportionate environmental injustices and are targeted due to systematic economic and political inequities. This research evaluates the ease at which links between industrial releases and risk of adverse health effects can be defined to influence policy change in Houston, TX. The Environmental Protection Agency (EPA)'s Toxic Release Inventory (TRI) is the most comprehensive public database on industrial facilities' toxic chemical releases in the US. TRI is presented within a risk-based context through the Risk Screening Environmental Indicators (RSEI) scores. TRI and RSEI datasets for Houston in 2022 were assessed in QGIS to analyze chemical release and risk in neighborhoods using Community Tabulation Areas (CTAs), identifying demographics of communities facing disproportionate industrial releases and consequent potential health risks. Geospatial visualizations reflected Latinx communities to house the heaviest polluting industrial facilities in Houston. As a result, these communities face the highest potential risk of adverse health effects due to exposure to a multitude of chemicals-particularly 1,3-butadiene, benzene, and chromium-as reflected in cumulative RSEI scores. An analysis of TRI and RSEI datasets elucidates the burden of gathering and analyzing chemical release data in a public health context, reflecting why change beginning at the local level can be difficult for under-resourced Latinx communities facing industrial pollution. Improving the accessibility and utility of the EPA resources will provide a resource to advocate for data-driven policy change.
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Alcohol use in Early Midlife: Findings from the Age 37 Follow-Up Assessment of the FinnTwin12 CohortThis paper provides an overview of the most recent assessment, collected in early midlife, of the FinnTwin12 cohort, a population-based study of Finnish twins born in 1983-1987. The twins were invited to complete an online survey assessing a range of variables, including physical and mental health, alcohol use and problems, other substance use, and early midlife environments (e.g., parenthood). In total, 2,085 individuals (~ 40% of the original sample) completed the survey (551 complete twin pairs, 58.7% female, 37.3% monozygotic, Mage = 37.2 years, SD = 1.47 years, age range = 34-39 years). Individuals who participated were more likely to be female, monozygotic, and have higher parental education and less hyperactivity/impulsivity and aggression at age 12 when compared to individuals who were invited but did not participate. Parental alcohol misuse and the twins' alcohol use and misuse at age 14 were not related to study retention. Alcohol misuse in early midlife was positively associated with nicotine dependence, lifetime use of cannabis and other drugs, trauma exposure, and depressive symptoms, and negatively associated with physical health and having biological children. These new data expand upon the wealth of measures collected as part of previous assessments, expanding the scope of work on the etiology and correlates of alcohol misuse within a longitudinal, genetically-informed framework. In addition to these new survey measures, we are planning an in-person assessment to collect physiological measurements and conduct additional in-depth phenotyping on a subset of twins who have been more intensively studied over the years.
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Generalized target behavior reductions and maintenance of effects following an augmented competing stimulus assessment sequenceCompeting stimulus assessments are one technology that aids in the development of treatment for automatically reinforced behavior. However, competing stimulus assessments do not always yield robust results. Stereotypic behaviors of different subtypes may require procedural modifications to successfully identify competing stimuli. The current investigation included functional analyses to determine whether participant responding aligned with proposed subtypes for such behaviors. Next, we implemented augmented competing-stimulus-assessment (A-CSA) procedures across target and generalization stimuli to determine whether (a) responding across either subtype was more likely to require intensive modifications and (b) the A-CSA procedures promoted generalized target behavior reduction within stimulus classes. Lastly, a treatment evaluation was conducted to determine the durability of these findings and the generalization of the reduced target behavior to other settings. The general applicability of the subtyping model remains unclear, but two participants demonstrated maintenance of competition effects.
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SELF-ASSEMBLING MULTIDOMAIN PROTEIN MICELLES FOR MOLECULAR IMAGING AND DRUG DELIVERYProteins are versatile biomacromolecules with strong self-assembly properties that play a vital role in virtually all forms of life. By taking advantage of these properties, it is possible to design biocompatible, biologically active materials that can be used for a range of biomedical purposes, such as molecular imaging as well as targeted drug delivery. Unlike many other material systems, proteins can be recombinantly expressed and purified with multiple functional domains encoded in a single gene, often eliminating the need for additional chemical conjugation steps. Here we describe the design and engineering of multidomain proteins containing at least one coiled-coil domain and one disordered elastin-like polypeptide domain per chain. These proteins spontaneously assemble into micelles in aqueous solution. By incorporating targeting peptides into the genetic sequence, we can additionally alter the pharmacokinetics and organ tropism of the resulting micelles. Chapter 1 provides a brief overview of the field of protein biomaterials, while Chapters 2-4 delve in the design and characterization of protein micelles with multiple functional domains. First, in Chapter 2, we devise a collagen-binding molecular imaging probe for the monitoring of metabolic associated steatohepatitis (MASH) disease progression. This probe, collagen type I-binding thermoresponsive assembled protein (Col1-TRAP), was first characterized in vitro before being used to study a mouse model of MASH. It was found to preferentially accumulate in the livers of mice with MASH compared to normal mice. Next, in Chapter 3, we investigate the effect of increasing the multiplicity of the coiled-coil domain on improving hydrophobic drug loading capacity and delivery efficiency. Increasing the number of repeats of the coiled-coil domain from 1 to 2 was found to increase the drug loading capacity by 1.7-fold while reducing micelle packing by 25%. This construct, targeted multidomain protein assembly (TMPA), was found to preferentially accumulate in tumor sites in mice implanted with glioblastoma xenografts. Finally, Chapter 4 focuses on the targeting of TMPA for specific drug delivery to HER2+ breast cancer by using the peptide P51. Targeted micelles loaded with doxorubicin displayed improved uptake into and cytotoxicity against breast cancer cells overexpressing the HER2 receptor, while showing no selectivity in triple-negative breast cancer cells. All micelle-drug formulations were found to be more effective than free drug alone, showing the utility of these protein materials.
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Brain, Environmental and Psychological Trauma: TBI and PTSD Markers, Mechanisms, and InteractionsTraumatic brain injury (TBI) and Post-traumatic stress disorder (PTSD) are significant public health concerns, particularly among individuals exposed to high-stress environments such as military combat. However, they can also occur anytime due to various head injuries and stress. This review examines the interplay between TBI and PTSD, highlighting their prevalence, symptoms, potential biomarkers, pathological mechanisms, and the interactions that occur with exposure to both conditions. Worldwide, an estimated 69 million individuals per year sustain TBI, while approximately 13 million people per year exhibit PTSD. Notably, PTSD is markedly higher among individuals with TBI, particularly in veterans, where an estimated 28% of patients with mild TBI also exhibit PTSD. Although each alone results in significant symptoms and pathology, the co-occurrence of PTSD and TBI exacerbates the situation due to overlapping symptoms and bidirectionally interacting pathological changes. The occurrence of both TBI and PTSD increased cognitive impairments, emotional dysregulation, and disability with reduced function and health. Here, I provide a synthesis of current literature and assess the relationships between TBI and PTSD. We draw upon clinical and preclinical data to provide this critical overview. TBI increases the risk of developing PTSD, and PTSD increases susceptibility to the consequences of TBI. This interaction is due primarily to several overlapping mechanisms, including disrupted fronto-limbic brain circuits, neuroinflammation, and dysregulation of the HPA axis and specific neurotransmitter systems. White matter and brain area changes affect neural connectivity and functioning. Stress systems, inflammation, neurotransmitter imbalances, and structural brain changes interact closely in both TBI and PTSD. For example, chronic stress dysregulates the HPA axis, amplifying neuroinflammation and altering cortisol levels, further impacting neurotransmitter systems like serotonin and dopamine. This biochemical cascade contributes to white matter degradation and reduced brain volume, especially in regions like the hippocampus and prefrontal cortex, worsening cognitive and emotional symptoms. These interconnected changes create a feedback loop that sustains dysfunction across neural networks, complicating recovery. These changes worsen cognitive and emotional symptoms and create a feedback loop that hinders recovery. Continued research is required to understand TBI and PTSD interactions better. Additional pathological mechanisms and targets for intervention using appropriately designed studies in experimental models and in the clinic. This “translational research” approach will help us discover future risk prevention, intervention, and rehabilitation strategies that can improve the quality of life for those impacted by these comorbid and disabling disorders.
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Impact of Health Home and transition of care programs on diabetic patients' care and health outcomesA small proportion of patients accounts for a disproportionately large share of healthcare spending, often due to multiple chronic conditions and frequent hospital use. In response, New York State implemented the Health Home (HH) program to improve care coordination and reduce unnecessary hospital utilization among high-need Medicaid enrollees. This study evaluated whether early and consistent access to Primary Care Providers (PCPs) and care coordinators through the HH program improves outcomes for patients with diabetes mellitus and high acute care use, specifically by reducing hospital admissions and shortening the length of stay for readmissions. A retrospective cohort study was conducted using electronic medical record (EMR) data from a major New York healthcare system, including 16,229 diabetic patients eligible for Health Home (HH) services. The data were limited to patients over the age of 19 who were eligible for Health Home services during hospital visits between June 1, 2018, and December 31, 2019. The objective was to evaluate whether the HH program, developed by New York State to improve outcomes for high-need Medicaid patients, is achieving its intended goals. The following outcome measures were explored: hospital readmissions within 60 days post-discharge, the number of days from discharge to readmission, and the length of stay for readmitted visits. Covariates included age group, gender, race/ethnicity, primary language, marital status, LACE index (Length of stay, Acuity of admission, Comorbidities, and recent Emergency department use), and comorbidities indicated by the Charlson Comorbidity Index (CCI). All analyses were conducted using SAS software. The study found that enrollment in Health Home (HH) was significantly associated with an increase in the likelihood of readmission within 60 days in the unadjusted model (estimate = 1.0720, p <0.0001). After adjusting for race/ethnicity, age range, LACE, and CCI as confounders, the association remained significant, though attenuated (estimate =0.923; p<0.0001). Regarding the number of days between index admission and readmission, the unadjusted model indicated that HH enrollment significantly decreased the days between index discharge and readmission within 60 days, with an estimated -1.22 days (p = 0.0234). However, after accounting for LACE and CCI as confounders, the association between HH enrollment and days to readmission was no longer statistically significant (estimate = - 0.86, p = 0.1122). Similarly, the association between HH enrollment and length of stay (LOS) for readmitted visits was positive (estimate 0. 234, p= 0. 044); however, after controlling for age group, LACE, and CCI as confounders, it was no longer statistically significant (p= 0.493) and the relationship was reversed (estimate = -0.077). The findings suggest that demographic factors (specifically race/ethnicity and patient age), prior high utilization of hospital services (indicated by LACE score), and clinical burden (as indicated by CCI) significantly influence readmission outcomesindependent of HH program enrollment. While the unadjusted associations appeared statistically significant, the adjusted models underscore the role of these confounders. The results highlight the need for more tailored interventions that account for patients' demographic and clinical risk profiles to improve outcomes among diabetic patients enrolled in the HH program.
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Sex differences in memory modulation by mTORC1 activationThe mechanistic target of rapamycin (mTOR) is a central regulator of several cellular processes that are required for learning and memory, through the mTOR complex 1 (mTORC1) signaling pathway. However, little is known about how mTORC1 signaling in the brain is affected by sex or disease. We previously reported that activation of mTORC1 by 3-benzyl-5- ((2-nitrophenoxy) methyl)–dihydrofuran-2(3H)-one (3BDO) upregulated hippocampal rRNA expression and enhanced memory on the hippocampal-dependent active place avoidance task in young wild-type (WT) male mice. Here, we set out to determine if mTORC1 activation by 3BDO could enhance or rescue learning and memory on the active place avoidance task in both male and female mice from two strains, WT and APP/PS1, a model of Alzheimer’s Disease (AD). We selected two age groups to analyze: 8–9-months-old, when plaques are established and deficits in spatial memory begin to appear in APP/PS1 mice, and 12–13-months-old, when plaques are extensive and memory is severally impaired in APP/PS1 mice. Our data showed that a single dose of 3BDO delivered systemically rescued memory in 8–9-months-old male APP/PS1 mice but did not significantly affect male WT mice at this age. Further, 3BDO improved latency during learning for 12–13-months-old male mice overall but did not impact memory at this age. Surprisingly, in female mice, we found that 3BDO impaired both learning and memory at 8–9-months-old in WT mice, while having no significant effect on 8–9-month-old APP/PS1 mice or 12–13-months-old mice of either genotype. After behavioral testing, we further analyzed the effects of 3BDO administration on mTOR expression by Western blot. In the dorsal hippocampus, we saw overall less mTOR and phosphorylated mTOR in females compared to males at 8–9-months-old, but overall more mTOR and phosphorylated mTOR in females compared to males at 12–13-months-old. These results challenge the current understanding of how mTORC1 functions in AD and provide a new avenue of research into potential therapeutics. At the same time, the opposing effects of 3BDO on males and females trained on the same learning and memory task highlight the importance of studying potential sex differences of emerging therapeutics.
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Minocycline plus N-acetylcysteine improve chronic and progressive structural and functional deficits following a single TBI in male miceTraumatic brain injury (TBI) is the leading cause of death and disability above any other trauma. The high prevalence of later life degenerative outcomes strongly suggests a single TBI can develop into a progressive neurodegenerative disorder. Clinical TBI may produce chronic deficits in limb coordination, and gait that is associated with corpus callosum damage. Detection of chronic motor deficits after TBI may be obscured by effects of aging or the development of compensatory motor strategies. Chronic motor deficits are poorly studied in rodent TBI models. The murine closed head injury (CHI) model produces diffuse, chronic white matter injury that may underlie chronic white matter dysfunction and motor deficits. DeepLabCutTM markerless limb tracking provided the data for novel assessments of limb function on beam walk and simple-complex wheel. Injured mice on beam walk do not differ from sham mice on time to traverse or foot fault number. Novel assay beam walk absition integrates time and extent of all foot faults during a beam walk trial. Injured mice have chronic absition deficits that are blocked by dosing of minocycline and N-acetylcysteine beginning 12 hours post injury (MN12). Absition deficits do not appear until 90 DPI and worsen at 180 DPI suggesting chronic and progressive motor decline. Speed is a standard method to assess performance on simple-complex wheel. Novel assays show that at 14 DPI, MN12 improves limb coordination to prevent an injury dependent decline in running speed. Ex-vivo T2 and diffusion-tensor MRI studies show that MN12 prevents most progressive gray and white matter atrophy in motor structures and improves bilateral white matter integrity. MN12 increases inflammatory cell density in corpus callosum after CHI. This increased inflammatory response is likely beneficial since MN12 improves callosal structure and function. Evoked compound action potentials (CAP) assess corpus callosum function from 3 to 180-days post injury (DPI). CHI acutely decreases CAP amplitudes that recover by 90 DPI and further increase at 180 DPI. Changes in CAP amplitude are blocked by MN12. CHI mice have chronic corpus callosum dysfunction that coincide with motor deficits. Analysis using DeepLabCutTM limb tracking reveals chronic deficits and compensatory motor strategies not seen with standard outcomes. These observations support the central hypothesis of this thesis: MINO plus NAC improves injury-dependent deficits in white matter histology, structure, and function with a favorable therapeutic time window in male mice, as well as the aim to test if MINO plus NAC reduce structural and functional deficits in white matter after a single CHI in male mice. The results of these experiments provide important information about the chronic phase of TBI in addition to developing novel methods to assay the onset, persistence, and progression of injury-dependent changes in the CHI mouse model of TBI.
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Thermoregulatory Stress and the Ageing Mind: Investigating Environmental High Heat Exposure as a Risk Factor for DementiaBackground As populations age globally, the health effects of extreme heat exposure are an increasing public health concern. This study examines the association between cumulative high heat exposure and the prevalence of Alzheimer’s Disease and Related Dementias (ADRD) and Mild Cognitive Impairment (MCI) among U.S. adults. Methods Data were obtained from the All of Us Research Program (n = 286,767). Heat exposure was assessed using data from the CDC’s National Environmental Public Health Tracking Network and mapped to 3-digit ZIP codes. Two exposure metrics were examined: (1) maximum temperature and (2) maximum heat index. High heat exposure was defined as the total number of extreme heat days (≥2 consecutive days with a maximum heat index above the 90th percentile for May–September) occurring within multi-day heat events from 2019 to 2023. ADRD/MCI diagnoses and medical comorbidities (cardiovascular disease, cerebrovascular disease, type 2 diabetes, chronic obstructive pulmonary disease, hearing impairment, and depression) were identified from electronic health records. Demographics, smoking, alcohol use, and social isolation were measured via survey. Socioeconomic status (SES) was assessed at both the individual level, using educational attainment, and at the community level, using the Area Deprivation Index (ADI). Logistic regression models estimated associations between high heat exposure and ADRD/MCI risk, adjusting for demographic, medical, and socioeconomic factors. Mediation analysis examined the role of SES and social isolation. Results Each additional extreme heat day was associated with a 0.39% increase in ADRD/MCI odds (95% CI: 1.0026–1.0051) when measured by maximum temperature, and a 0.58% increase (95% CI: 1.0044–1.0071) when measured by maximum heat index. Exposure to 10 extreme heat days within multi-day heat events was associated with approximately a 4% increase in the odds of ADRD/MCI when measured by maximum temperature, and approximately a 6% increase when measured by maximum heat index. These findings indicate that sustained heat exposure has a cumulative impact on cognitive risk. The association was stronger when exposure was assessed using heat index rather than temperature alone, suggesting that humidity exacerbates heat-related cognitive risks. Mediation analysis found that ADI accounted for 8.6%–9.6% of the total effect; however, high heat exposure remained a significant independent risk factor for ADRD/MCI. Neither educational attainment (as a proxy for individual-level SES) nor social isolation significantly mediated or moderated the observed associations. Discussion These findings highlight an association between sustained extreme heat exposure and ADRD/MCI, with stronger effects observed when using heat index, suggesting humidity may exacerbate heat-related cognitive vulnerability. Area deprivation partially mediated this association, reinforcing how environmental and social inequities jointly shape cognitive health. Older adults are particularly vulnerable, and disparities in access to cooling resources may compound these risks. The urban heat island effect may further amplify exposure, underscoring the need for targeted public health interventions, such as early warning systems, urban planning strategies, and equitable access to cooling. Increasing heat exposure calls for public health approaches that recognize its potential impact on cognitive decline, especially among structurally disadvantaged populations. Given the absence of disease-modifying treatments for ADRD/MCI, addressing modifiable environmental risks remains essential to protect cognitive health in an ageing population
