From preclinical models to public health: mechanistic and translational insights into fentanyl and polysubstance effects on sleep, respiratory function, and overdose

2026The escalating crisis of opioid overdose, driven largely by fentanyl and increasingly complicated by polysubstance use, presents challenges to public health and clinical practice. This dissertation provides a transdisciplinary investigation into the impact of fentanyl and its co-administration with other substances on sleep–wake architecture, respiratory function, neurobiology, molecular pathways, and the effectiveness of post-overdose outreach interventions. Using piezoelectric monitoring and polysomnography in mouse models, I demonstrated that both acute and chronic fentanyl exposure markedly reduced non-rapid eye movement sleep, with subtler but persistent rapid eye movement sleep disruptions following opioid cessation. The complexity of opioid-induced sleep disruption is further magnified by the widespread adulteration of fentanyl with xylazine. Fentanyl–xylazine co-exposure produced sex-dependent alterations in sleep, including reduced non-rapid eye movement sleep recovery, shortened bout duration, altered rapid eye movement sleep dynamics, and exacerbated respiratory depression, particularly in males. Pharmacological antagonism with yohimbine partially reversed these effects, implicating α2-adrenergic receptor mechanisms. At the circuit level, the locus coeruleus, a key addiction and sleep hub containing both α2-adrenergic receptors and μ-opioid receptors, displayed upregulated μ-opioid receptor expression only after fentanyl or xylazine exposure, which normalized under co-administration, suggesting complex α2-adrenergic driven μ-opioid receptor adaptations. In parallel, serum proteomic analyses highlighted fibroblast growth factor 21 as a potential regulator at the intersection of sleep, metabolism, and substance use. Polysubstance use also poses challenges and critical gaps in knowledge at the public health level. Evaluation of Massachusetts post-overdose outreach programs revealed that a subset of programs had begun conducting stimulant outreach, in addition to opioids, reflecting the changing overdose landscape. Programs that adapted to these shifts in use were those engaging Black, Latine, Native, and youth populations while maintaining strong harm reduction practices—highlighting the importance of flexibility and cultural responsiveness in community-based interventions. Thus, this dissertation provides foundational knowledge on the neurobiological and public health consequences of fentanyl and polysubstance misuse, offering actionable pathways for future research that may improve clinical care and community interventions in the ongoing effort to mitigate overdose and enhance recovery

Play to connect: supporting social and emotional development in children on the autism spectrum through caregiver-guided pretend play

2026Children on the autism spectrum engage with others in diverse ways, and differences in social skills can make early social experiences challenging especially when support is not tailored to their needs. Although many preschools in Singapore offer universal social-emotional learning (SEL) programs, these often lack a caregiver component and rarely use play-based approaches, limiting their effectiveness for children on the spectrum. Caregivers, who play a central role in supporting their child’s social participation, frequently receive little guidance on how to do so. This gap can increase caregiver stress and negatively affect their overall well-being. Play to Connect is an evidence-based, fully online program for caregivers of preschool children on the autism spectrum. It is delivered over three months by trained occupational therapists and provides caregivers with the knowledge, skills and confidence to engage their children in pretend play to support the development of social-emotional skills in everyday routines. Developing contextually relevant programs like Play to Connect addresses the unique challenges faced by caregivers in Singapore, offering targeted support that enhances caregiver self-efficacy. By strengthening caregivers' skills and confidence, Play to Connect supports caregiver well-being and promotes positive developmental outcomes for children on the autism spectrum

Exploring patient activation among dual-eligible Medicare beneficiaries: studies on the impact of enrollment in dual-eligible special needs plans and care coordination on activation and self-managed care

2026Individuals enrolled in both Medicare and Medicaid, or dual-eligible beneficiaries, face complex health and social challenges, including poverty, disability, and unmet social needs. Compared to Medicare-only beneficiaries, they report poorer health, lower educational attainment, greater functional limitations, and higher post-acute care. Although they represent only 19% of the Medicare population, they account for 34.5% of Medicare spending. Dual-Eligible Special Needs Plans (D-SNPs) were created to align Medicare and Medicaid benefits, improve care coordination, and reduce fragmentation. Within this context, patient activation—the knowledge, skills, and confidence to manage one’s health—is critical for promoting self-management, improving outcomes, and reducing costs. Yet little is known about how activation differs by dual-eligibility or plan type, or how care coordination shapes activation for this population. This dissertation used a sequential, multiphase mixed-methods design to examine relationships among dual-eligibility, D-SNP enrollment, care coordination, and patient activation. Quantitative analyses using Medicare survey data employed Fairlie decomposition, propensity scores, and inverse probability weighting to compare activation between dual-eligible and Medicare-only beneficiaries and assess whether D-SNP enrollment was associated with higher activation. Qualitative interviews with care coordinators explored how coordination practices foster activation within these contexts. Quantitative findings showed dual-eligible beneficiaries had significantly lower activation, largely explained by social risk such as low education attainment. Explanatory factors differed by subgroup: for older dual-eligibles, limited English proficiency, living alone, poor perceived health, depression, anxiety, vision impairment, and limitations in activities of daily living (ADLs); for disabled dual-eligibles, intellectual disability and limitations in instrumental ADLs. D-SNP enrollment was associated with lower activation compared to Medicare Advantage, though similar to traditional Medicare. Notably, D-SNP enrollment was associated with lower activation among disabled and historically marginalized dual-eligibles, particularly, non-Hispanic Black enrollees. Qualitative analyses of care coordinators working with dual-eligible beneficiaries identified themes aligned with the Information-Motivation-Behavioral Skills model: (1) relational trust as a catalyst for engagement; (2) seeing the whole person, not the diagnosis; (3) personalization and adaptation in communication; (4) active confirmation of patient comprehension; and (5) collaborative problem-solving and momentum building. Practice and policy implications for dual-eligible beneficiaries include tailoring outreach strategies to specific subgroups, integrating patient activation into the D-SNP Model of Care, and ensuring comprehensive teach-back techniques are embedded within provider practices to reinforce comprehension of self-management behaviors. Systematically addressing modifiable risk factors may enhance activation, equity, and quality of life for high-need Medicare populations.2028-01-15T00:00:00

Scavenging behavior of vertebrates and invertebrates on rabbit (Oryctolagus cuniculus) carrion in a New England environment

2026Forensic entomology is the use of arthropods and their ecology to answer legal questions. Arthropods, along with vertebrate scavengers, temperature, and other abiotic conditions, play an important role in the rate of decomposition. It is important for forensic professionals to consider these factors when it comes to interpreting the evidence found on a scene. The present research objectives were to: (1) investigate the effects of Late Spring (April/May) and Early Autumn (September) on scavenging behaviors in an anthropogenic protected wooded/wetland ecosystems; (2) observe the influence of vertebrate scavenging on rabbit (Oryctolagus cuniculus) carrion; and (3) quantify the production of flies from rabbit carrion in anthropogenic protected wooded/wetland ecosystems. It was hypothesized that vertebrate scavengers will have a greater effect on the decomposition rate compared to invertebrate scavengers. The sample size for this study consisted of 14 rabbit carcasses. Rabbit carcasses were placed at the Outdoor Research Facility (ORF) at Holliston, MA and Curry College’s campus at Milton, MA. The rabbit carcasses were placed in eight different locations total from both sites. Vertebrate scavengers were recorded via Digital Trail Camera SL112 and GardePro Trail Camera A3S models. Invertebrate scavengers were collected from the carrion and quantified. The results for the study proved the hypothesis correctly. The results showed that vertebrate scavengers had a greater influence on the decomposition rate compared to invertebrate scavengers. The vertebrate scavengers that had a greater influence were probable Virginia opossums (Didelphis virginiana), Eastern phoebe (cf. Sayornis phoebe), and coyotes (Canis latrans). The invertebrate scavengers that were collected at both sites include Phormia regina (Meigen) (Diptera: Calliphoridae) and Lucilia sericata (Meigen) (Diptera: Calliphoridae). Curry College’s campus on average had more larvae present on the carrion (32,890) compared to the ORF (25,263). While the ORF had more adult flies present on the carrion (337) compared to Curry College’s campus (68). There is no significant difference in the number of larvae and adult flies from both sites (0.744)

Establishing an occupational therapy program for acute and chronic care in Trinidad and Tobago: a practical roadmap for implementation

2026Non-communicable diseases (NCDs), including stroke, diabetes, and cancer, are the leading contributors to disability in Trinidad and Tobago. Although early and continuous rehabilitation improves recovery and reduces long-term functional decline, national rehabilitation services remain fragmented, with minimal occupational therapy (OT) presence in acute care and inconsistent support in community settings. The absence of structured pathways from hospital to home contributes to preventable dependence, poor functional outcomes, and increased burden on families and the health system. Sankofa Rehab T&T is a culturally responsive OT initiative designed to address these gaps by integrating rehabilitation across acute and chronic care pathways. The model combines early hospital-based OT, home and community rehabilitation, caregiver education, workforce training, and digital monitoring. It aims to restore functional independence for individuals with NCDs while strengthening national rehabilitation capacity and generating actionable data to inform policy.The project uses a mixed-methods, three-phase evaluation framework: Phase One focuses on tool validation and stakeholder alignment; Phase Two examines implementation processes; and Phase Three evaluates outcomes using pre- and post-intervention measures. Quantitative indicators include reach, fidelity, functional outcomes, readmission rates, and training outputs, while qualitative data explore cultural fit, relevance, and lived experience. Anticipated impacts include earlier OT involvement, improved daily living skills, increased caregiver confidence, and reductions in preventable disability. A two-year financial and dissemination plan supports implementation, scalability, and policy translation. The Sankofa model offers a feasible, culturally grounded, and sustainable approach to embedding OT within national NCD care for the first time, addressing longstanding service gaps and advancing equitable rehabilitation access in Trinidad and Tobago.

Effects of Medicaid expansion and state inclusionary policies on immigrant health and healthcare use in the United States

2026The United States is home to an estimated 51.9 million immigrants, a growing population that experiences substantial disparities in health insurance coverage and access to care. These disparities are shaped and perpetuated, in part, by a complex and often exclusionary policy environment, exemplified by recurrent changes to the public charge rule and the recent enactment of the One Big Beautiful Bill Act (OBBBA). Among the most consequential policies reinforcing these barriers is the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996, which bars legal immigrants from accessing public benefits including Medicaid, Children’s Health Insurance Program (CHIP), Temporary Assistance for Needy Families (TANF), Supplemental Nutrition Assistance Program (SNAP), and Supplemental Security Income (SSI) during their first five years in the U.S., a restriction commonly known as the “five-year bar”. PRWORA also replaced the Aid to Families with Dependent Children (AFDC) entitlement program with the TANF block grant, and added complexity to the determination of benefit eligibility through the strict definition of “qualified alien”. The effects of PRWORA extend beyond immigrants themselves, impacting U.S.-born children in mixed-status households. Although the vast majority of children in mixed-status families are U.S. citizens (88%) and therefore eligible for public benefits, their access and experience is often undermined by the restrictive provisions of PRWORA and the chilling effects of related immigration policies. In response, there have been efforts to improve healthcare access for immigrants through the adoption of Medicaid expansion under the Patient Protection and Affordable Care Act (ACA), as well as inclusionary state Medicaid policies providing coverage to otherwise ineligible immigrants by using state or local funds. Despite these efforts, the uptake of public benefits remains low among eligible immigrants and U.S.-born children in mixed-status households—often due to the fears of immigration-related consequences, especially in light of recent changes to the public charge rule and rising anti-immigrant sentiment. In 2023, an estimated 18 percent of lawfully present immigrant adults were uninsured compared to 8 percent of U.S.-born adults. Among U.S. citizen children, 4 percent were uninsured among those with U.S. citizen parents compared to 8 percent among those with noncitizen parents, demonstrating that disparities based on immigration status persist decades after PRWORA. Similarly, following changes to the public charge rule, participation in critical food and nutrition programs like SNAP and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) declined among households with immigrant parents as compared to those with U.S.-born parents. This dissertation evaluates the compounding impact of federal and state health insurance policies—specifically PRWORA, Medicaid expansion, and inclusionary state Medicaid policies—on healthcare utilization, total healthcare expenditures, health outcomes, and experiences of care among multigenerational immigrant families. Guided by the Social Determinants of Health Framework, this research leveraged multiple years of restricted-use data from the Agency for Healthcare Research and Quality (AHRQ), linking the Centers for Disease Control and Prevention’s National Health Interview Survey (NHIS) with AHRQ’s Medical Expenditure Panel Survey (MEPS), along with state policy data from the Urban Institute State Immigration Policy Resource (SIPR). The long-term goal of this research is to strengthen the evidence base on the impact of health and social policies on immigrants and their families in the United States. Chapter 1 provides a review of the literature motivating this work, including a historical overview of U.S. immigration policy with a particular focus on PRWORA and its implications for public benefit use across generations. Chapters 2 through 4 present the three specific aims of the dissertation. Chapter 2, To Quantify Differences in Immigrant Adult Healthcare Use and Expenditures Following Medicaid Expansion, examined changes in healthcare utilization and expenditures following Medicaid expansion among immigrant adults based on years of residence in the U.S. Chapter 3, To Identify the Effect of Inclusionary State Medicaid Policies on the Physical and Mental Health of Immigrant Adults, assessed changes in physical and mental health functioning associated with the adoption of inclusionary state Medicaid policies among immigrant adults based on years of residence in the U.S. Chapter 4, To Assess the Timely Receipt of and Experience of Care for Children of Immigrants Following Medicaid Expansion, evaluated differences in the quality of care for children following Medicaid expansion based on household immigration status. Chapter 5 provides concluding remarks on the findings of Chapters 2 through 4, as well as directions for future research

The power of play: enhancing parental engagement and child development through an occupational therapy guided community play space

2026Developmental play is critical in developing a child’s cognitive, social-emotional, social, and physical skills and in establishing foundational skills that a child will access throughout their life. Parents play an important role in facilitating meaningful play experience that support a robust development for children; however, many parents face barriers impacting engagement in developmental play such as limited awareness of the importance of play, parental stress, or difficulties with resources to enhance play. Honeycomb Cafe and Busy Bees Play Space is an occupational therapy-informed, community-based program designed to foster connections, education, and confidence. Through educational courses, parent workshops, and many other offerings, the play cafe will assist in promoting parent-child engagement and enhancing interactions. The pilot study is a six-week educational series “The Ins and Outs of Tummy Time” which targets increasing parental confidence, strengthening parent/child interactions, and reducing parental stress. The program is one component of a larger vision to affect positive change in the local community

Identification and characterization of a lipopolysaccharide binding, anti-inflammatory protein from Parabacteroides distasonis

2026-02-28T00:00:00

Development and application of proteomics-based tools for ligand target identification

2026Small molecules are the foundation of modern pharmacology, yet defining their direct protein targets in the complex environment of the cell continues to challenge chemical biology. This dissertation describes the development and application of proteomics-based tools that capture ligand-protein interactions through complementary readouts of stability, conformational change, and adsorption at material interfaces. Together, these approaches extend the scope of chemoproteomics beyond conventional formats and enable the discovery of targets and mechanisms that would otherwise remain hidden. Following a general introduction in Chapter 1, the dissertation is organized into three major research efforts presented in Chapters 2 through 4.Chapter 2 establishes an approach for the discovery of ribonucleoprotein-targeted interfacial ligands. Rocaglates, acting as proximity inducers, clamp RNA to DEAD-box helicases, a mode of inhibition that depends on multicomponent assembly rather than a single binary interaction. Using proteome-wide stability assays, I demonstrate how tailoring biochemical conditions with nucleotide analogs and RNA substrates can reveal substrate-dependent interactions otherwise inaccessible, expanding the known rocaglate clamping spectrum more than two-fold. Chapter 3 explores bioactive scaffold tunability in a disease context. Through comprehensive chemoproteomic profiling of rocaglate acyl sulfamides, I show that subtle structural changes at chemically permissive sites shift rocaglate selectivity toward DDX3X, a helicase whose engagement correlates with selective cytotoxicity in glioblastoma stem cells. Comparative proteomic assays and structural modeling converge to explain this bias, establishing these compounds as context-specific chemical probes. Chapter 4 introduces ILIAD (Identifying Ligand Interactions through Adsorption Differences), a new derivatization-free chemoproteomic platform that reframes protein adsorption to labware surfaces as a readout of target engagement. ILIAD detects both broad remodeling with nucleotide analogs and selective engagement by tool compounds and drugs, demonstrating that adsorption can serve as an orthogonal signature of ligand binding. Building sequentially across the three research chapters, this dissertation demonstrates how chemical context, scaffold modification, and reframing can be leveraged to expand the chemoproteomic toolkit. The approaches developed here illustrate a path toward more complete mapping of drug-protein interactions and provide conceptual and methodological advances relevant to both probe discovery and therapeutic development.2028-01-22T00:00:00

TGF-β1-dependent expression of FOXS1 attenuates adipogenic potential and enhances a myofibroblast cellular phenotype

2026White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASC). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as an early transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several activated myofibroblast genes (e.g. Acta2, Col1a1, Fn1, Il11) in 10T1/2 fibroblasts. FOXS1 also mitigated the dexamethasone, 3-isobutyl-1-methylxanthine, insulin, and indomethacin (DMII) induced upregulation of several adipogenic factors (e.g. Pparg, Stat5a, Fabp4, Adipoq) and sensitized cells to the anti-adipogenic effects of TGF-β1. Furthermore, loss of endogenous FOXS1 improved 10T1/2 adipogenic permissiveness and activated proadipogenic gene programs, even after TGF-β1 stimulation. These results indicate that FOXS1 is a positive regulator of profibrotic TGF-β1-dependent cellular responses, orchestrating profibrotic and anti-adipogenic molecular phenotypes that promote myofibroblast activation and block adipogenesis. These findings offer novel insight into the TGF-β1-dependent roles of FOXS1 in fibroblasts within the context of profibrotic WAT ASC activation and provide a foundation for further investigation into the role of FOXS1 in WAT fibrosis and obesity-induced cardiometabolic dysfunction