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Effectiveness of treatment strategies for multdrug resistant tuberculosis
No full text2026Tuberculosis is one of the leading causes of infectious disease deaths worldwide, and multidrug resistant tuberculosis (MDR-TB) is a threat to its control. As it is resistant to the most effective first-line drugs, its treatment requires use of several second-line drugs that are less effective and can be highly toxic. In recent years, the WHO’s recommendations have been updated to prioritize regimens that use oral medications rather than injectables and ones that do not have to be taken for as long as in the past. The probability of successful treatment outcomes may be decreased by difficulty in adhering to regimens as well as emergence of resistance to second-line agents. In this dissertation, we aim to identify characteristics of participants and treatment regimens that promote successful outcomes. First, we attempt to identify participants that are adherent or non-adherent to regimens using a latent class analysis method. We analyzed data from the Predictors of resistance emergence evaluation in multidrug resistant-tuberculosis patients on treatment (PREEMPT) study, a prospective cohort study of people on treatment for MDR-TB and found that about 80% of the study population were expected to be fully adherent. Then, we assessed the effectiveness of different treatment regimens by examining whether treatment outcomes differ by WHO-recommended treatment regimens. Using the PREEMPT cohort, we found that the longer-term regimens appeared to prevent unsuccessful treatment outcomes but that newer generation drugs might improve outcomes. Finally, we attempted to identify predictors of emergence of resistance to second-line drugs while on treatment. We trained a prediction model using a least absolute shrinkage and selection operator (lasso) model on the Preserving effective tuberculosis treatment (PETTS) cohort study, a study of people on treatment for MDR-TB. We used the PREEMPT data as well as a clinical trial of delamanid vs. standard of care for MDR-TB to validate our prediction model. We found that creation of a well-validated prediction model for emergence of resistance is difficult to achieve because of the rarity of the outcome in our datasets. In summary, we identified a subpopulation of individuals who are less likely to fully adhere to MDR-TB treatment, effectiveness of longer-term WHO regimens, and difficulty of predicting emergence of resistance to second-line TB medications.2028-01-15T00:00:00
From preclinical models to public health: mechanistic and translational insights into fentanyl and polysubstance effects on sleep, respiratory function, and overdose
Full text link2026The 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
Assessing the role of leptin-receptor neurons in the dorsomedial hypothalamus in the circadian release of glucocorticoids in mice
Full text link2026Circadian rhythms are coordinated by the suprachiasmatic nucleus (SCN), which orchestrates daily changes in behavior and physiology. Glucocorticoids (Cort), which have been classically studied in the context of stress, are released into the circulation from the adrenal glands on a 24-hour circadian cycle, with peak levels just around the time of awakening each day, and reaching a trough toward the end of the active period. This cycle of basal levels of corticosteroids is regulated by the SCN, the brain’s circadian clock. The dorsomedial hypothalamus (DMH) acts as an intermediary in this circuit, because of its abilities to integrate temporal information from the SCN and to activate stress responses through stimulating corticoptropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVHCRH neurons). Previous results found that ablating DMH gamma-aminobutyric acid (GABA)ergic neurons resulted in the flattening of glucocorticoid rhythms in mice, though it was not identified which subpopulation of these neurons was involved. The leptin-receptor expressing neurons in the DMH (DMHLepR neurons) are a GABAergic population that strongly responds to temporal metabolic cues. In this study, we aimed to assess the role that DMHLepR neurons have in regulating the circadian rhythms of glucocorticoids, locomotor activity (LMA), body temperature (Tb), and food intake, and to examine their role in the stress response. Selectively ablating DMHLepR neurons in mice prevented the daily rise of Cort under constant darkness, but not in a light/dark cycle, and decreased rhythms of LMA in both photoperiods. In addition, there was a slight decrease in Tb during the transition to the active period of the mouse. We did not observe any changes in food intake, or in the glucocorticoid secretion and LMA during a stress response. These results suggest that the DMHLepR neurons have a role in the endogenous regulation of glucocorticoid rhythms and locomotion but are less involved in the regulation of body temperature rhythms
Investigating access to HIV Prevention Services in the San Diego County bi-national (United States - Mexico) border region
No full text2026BACKGROUND: HIV is a public health concern across San Diego County. San Diego County has made significant progress reducing new HIV infections and improving outcomes of people living with HIV over the last 10 years. However, HIV infection targets outlined in the local Ending the HIV Epidemic Initiative plan are not on track to be met by their 2030 deadline. Several population groups continue to be disproportionately impacted by HIV in the San Diego County region. These vulnerable groups include but are not limited to transgender people. METHODS: This dissertation research was guided by the Situated Vulnerabilities and Resiliencies Framework (SVRF). Systematic scoping review methods were used to identify the primary barriers and facilitators to accessing HIV prevention services in the San Diego County binational region. SVRF vulnerability domains, scoping review results and Geographic Information System methods were used to develop a localized HIV Prevention Vulnerability Index (HVI) to identify geographic areas that lack HIV services. An HVI guide was then developed to demonstrate how and why to use the HVI. RESULTS: Seven core characteristics of HIV prevention services for transgender people in San Diego County were identified in the scoping review. Although improvements have been made, transgender inclusion in local research and decision-making remains limited. Increased representation is needed to better understand transgender-specific needs and improve research and program planning. The HVI demonstrated how social, economic, and environmental factors significantly impact geographical HIV vulnerability across the county. HVI analysis revealed local service barriers including geographic service availability, urban-rural differences, and racially driven healthcare disparities. An HVI user guide identified how public health and service delivery providers can apply the Index in local decision-making processes. CONCLUSION: This dissertation emphasized the importance of understanding geographic context and the specific characteristics and needs of vulnerable populations when planning and delivering HIV prevention initiatives. The approaches presented in this dissertation can be adapted in other local health jurisdictions to improve services for vulnerable communities. Research findings can also help local health officials identify gaps in surveillance systems and community strengths, and develop an enhanced understanding of localized health-related needs.2027-01-16T00:00:00
The power of play: enhancing parental engagement and child development through an occupational therapy guided community play space
Full text link2026Developmental 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
Eye-hand coordination: factors influencing gaze patterns during fingerspelling perception in American Sign Language
Full text link2026Sign languages such as American Sign Language (ASL) unfold dynamically over time, requiring perceivers to make real-time decisions about where to direct their gaze to capture linguistic information as it occurs and before it disappears. While skilled deaf signers look mostly at the face during sign perception, gaze is sometimes directed to the hands when fingerspelling occurs. I conducted three experiments to explore how different features of the input (familiarity, predictability) and cues from the sign producer (mouthing and indexing to the fingerspelling hand) impact looks to the hands during fingerspelling perception. In Study 1, I compare the role of sign type (lexical signs vs. fingerspelled words) and familiarity (novel vs. familiar) on deaf signers’ gaze patterns while perceiving single sign video clips, finding that sign perceivers look more at the hands when viewing fingerspelled words and novel items. In Study 2, I explore how cues from the sign producer (mouthing and indexing, when the sign producer looks at and points to their own hand during fingerspelling) impact gaze patterns, finding that, while mouthing results in more looks to the face, indexing does not increase looks to the hands. In Study 3, I explore the role of prediction on gaze patterns within a sentence context, finding that signers make anticipatory looks when they expect fingerspelling to occur but are unable to predict the specific word that will be produced, such as during the introduction of a name. This dissertation provides evidence that sign perceivers flexibly adapt their gaze based on both the perceptual and linguistic demands of the input. Pairing eye-tracking methodology with the visual modality of ASL offers insight into language processing and prediction, showcasing how language users dynamically attend to certain features of the linguistic input in real-time
Building education for affirming care of neurodivergent patients (BEACON)
Full text link2026Compared to allistic (nonautistic) individuals, autistic patients have difficulty achieving equitable engagement in the health management occupation, resulting in poor health, well-being, and service-use outcomes due to a lack of neurodiversity-affirming care within U.S. health care systems. Patient-level access barriers include physiological stress and anxiety pathway differences, reduced communication and regulation abilities when stressed, previous health care traumas, and concerns about providers’ perceptions. System-level factors include limited autism specific knowledge among health care providers, inflexibility among providers and practice policies and procedures, dysregulating environments, and a perpetuation of ableism. Aiming to improve access to and engagement in affirming health care, the Building Education for Affirming Care of Neurodivergent patients (BEACON) Comprehensive Clinic Guide (CCG) pilot program addresses inadequate knowledge of and access to education on autism within primary care by using highly relevant, role-specific, tiered, and multimodal educational guides. The BEACON program is unique in tackling system-level barriers, facilitating and measuring postintervention behavior change, and highlighting occupational therapy practitioners’ roles beyond traditional occupational therapy settings.
The BEACON program’s pilot test will enroll three privately owned primary care practices, and their staff will engage in guides specific to their roles within the practice. The pilot mixed-methods evaluation design includes pre- and postintervention surveys and a postintervention, formative focus group. Health care providers will also complete standardized efficacy scales before and after the course. These BEACON CCG learners will demonstrate improved knowledge of autism, better understanding of how to deliver affirming care, and increased desire to make behavior changes toward affirming care. By actualizing behavior, policy, procedure, and environmental modifications, the pilot clinics will improve access to affirming care for their autistic patients 3 months postcourse
The impact of pneumococcal conjugate vaccines on serotype prevalence, proportion, and antibiotic susceptibility of streptococcus pneumoniae among children 0 to 84 months from 2004 through 2023 at Boston Medical Center
No full text2026INTRODUCTION: The impact of pneumococcal conjugate vaccines (PCV) on nasopharyngeal (NP) carriage provides insight into the potential for herd effect, serotypes that may emerge in ‘replacement’ disease, as well as likelihood of cross-protection against nonvaccine serotypes.
METHODS: We analyzed NP colonization from 8 studies in Massachusetts’s children with similar experimental design performed between 2004-2023. Four studies (2004, 2007, 2009 and 2011) enrolled from 9 Massachusetts’s medical centers; 4 studies (2006-2007, 2010-2013, 2015-2017, and 2021-2023) enrolled at Boston Medical Center. NP swabs were collected from children between 0 and 84 months seeking well child or urgent care between October and April at their primary care site. NP samples were processed using WHO methodology.
RESULTS: Carriage prevalence and proportion of pneumococci by serotype grouping [PCV7, PCV13 unique + 6C, PCV20-additional, and nonvaccine serotypes and individual serotypes were analyzed for each study. A composite analysis of the data was created for the 20-year period. Comparing prevalence and proportion of pneumococci by serotype grouping demonstrates that while prevalence may be static or decreasing, the proportion for a specific serotype or grouping can increase. The prevalence of nonvaccine serotypes, specifically 35B, 23A and 23B, and 15A have not changed over the 20 years.
CONCLUSIONS: Prevalence of PCV7 and PCV13+ 6C serotypes declined rapidly following introduction of PCV7 and PCV13 vaccines. PCV20-additional serotype prevalence fluctuated by year but represents an increased proportion of pneumococci in the NP. Tracking individual serotypes confirms lack of cross reactivity between 23F and 23A and 23B, 9V and 9N, and 7F and 7
Polyphosphates interfere with the host immunity in Legionella infection
Full text link2026Legionnaire’s disease, caused by Legionella bacteria, is uncommon but serious cause of community-acquired pneumonia. Legionella resides within alveolar macrophages of infected hosts, where it releases effector molecules to evade phagocytic clearance. One of these molecules is predicted to be polyphosphates, which are produced by bacteria to help prolong their survival in hosts. Previous work has reported that long-chain polyphosphates derived from Escherichia coli interfere with the host innate response against infection. Here, I hypothesize that a similar mechanism occurs during Legionella infection. Macrophages derived from bone marrow of C57BL/6J mice were infected in vitro with Legionella pneumophila in the presence of purified polyphosphates. Additionally, polyphosphate levels were found to be elevated in human Legionellosis, murine Legionellosis, and in bone marrow-derived macrophage infection. In bulk RNA sequencing, the expression patterns of inflammatory response genes were mostly downregulated by long-chain polyphosphates (Pi 700). Specifically, interleukin-12 (IL-12) family cytokines and their signaling pathways (including signal transducer and activator of transcription (STAT) 1, STAT2 and STAT3) were suppressed by polyphosphates during Legionella pneumophila infection. IL-12 is a proinflammatory cytokine promoting type 1 T helper cell (Th1) polarization and, together with interleukin-18 (IL-18), induces interferon-γ production by natural killer (NK) and T cells, which are essential for the clearance of Legionella. The inhibition of IL-12 expression and release was confirmed by semi quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Polyphosphates cause a durable antagonism of IL-12 by 70% after 48 hours of infection in a chain-length-dependent manner.
A potential signaling pathway involving toll-like receptor 4 (TLR4) with myeloid differentiation primary response 88 (MyD88) and activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) cascade by polyphosphates was investigated. It was also confirmed that IL-18 and interleukin-1β (IL-1β) release, both cytokines produced by inflammasome activation and important for host defense against Legionella, were not affected by polyphosphates.
In conclusion, the presented studies provide novel evidence that long-chain polyphosphates specifically interfere with the IL-12-mediated immune response of macrophages against Legionella infection
Acceptance of wearable assistive technologies in an occupational therapy intervention to prevent and detect falls in older adults living in remote Nigerian villages
Full text link2026Falls are a leading cause of injury, disability, and loss of independence among older adults worldwide, with particularly severe consequences in underserved rural Nigerian villages where healthcare access, infrastructure, and emergency response systems are limited. This doctoral project, Acceptance of Wearable Assistive Technologies in an Occupational Therapy Intervention to Prevent and Detect Falls in Older Adults Living Alone in Remote Nigerian Villages, introduces a unique creative approach to addressing an urgent public health challenge. The author’s purpose was to design, implement, and evaluate a culturally responsive, occupational therapy led intervention that integrates traditional fall prevention applications⸺ environmental modifications, strength and balance exercises, and caregiver engagement⸺ with introduction of wearable fall detection devices that will optimize response time to a fall occurrence. The latter aspect of the project will be guided by established technology acceptance and health belief theories. Evaluation research for the anticipated 6-month pilot launch of the project will explore pre- and post-program numerical self-ratings of understanding, acceptance, and willingness to adopt both fall prevention and fall detection aspects of the program, as well as current anxiety, fear of falling, and quality of life. Focus groups and semi-structured interviews will gather information on participants’ qualitative experiences and reflections on program content and delivery. Key program goals for this culturally grounded community initiative are development of multilingual training materials, provision of free solar powered chargers, and establishment of community champions. The author’s vision is to offer a replicable model for elder empowerment and healthy aging in underserved populations and to expand the occupational therapy role in fall prevention and detection in low resource settings, thereby positioning this project as a step toward sustainable, community‑driven solutions for elder safety in Nigeria and Africa in general.