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Short-Term Intervention Effects on Distress, Inflammation, and Cognitive Functioning in Middle-Aged and Older Women with Breast Cancer
No full textAn estimated 75% of women diagnosed with breast cancer who receive treatment experience cancer-related cognitive impairment (CRCI), with up to 35% continuing to report symptoms months or years after treatment. Psychological distress and inflammation have been associated with CRCI; however, underlying mechanisms remain unclear. Given that most women diagnosed with breast cancer are over age 50 and transition into survivorship, further research is needed to understand how breast cancer exacerbates cognitive decline, particularly in the context of normal aging. Previous research has examined interventions such as cognitive behavioral therapy (CBT) and relaxation training for improving cognitive functioning, but none have tested the efficacy of an intervention that encompasses both elements, such as a remotely-delivered cognitive-behavioral stress management (R-CBSM) intervention. This study examined the effects of a 10-week R-CBSM intervention (compared to a wait-list control [WLC]) on subjective cognitive functioning in women (>50 years) with breast cancer and whether changes in breast cancer-specific distress and inflammation mediate intervention effects from baseline to 6-month follow-up. Women (N=101) with non-metastatic breast cancer were randomized to R-CBSM (N=51) or WLC (N=50). Participants completed psychosocial batteries and blood draws at baseline and 6-month follow-up. Results revealed no significant differences in cognitive functioning, distress, or inflammation between study conditions. Across the sample, cognitive functioning worsened, distress improved, and inflammation remained unchanged over time. Exploratory moderation analysis revealed that R-CBSM participants with moderate-to-high post-intervention distress had a significant cognitive decline; those with low distress had no change. Among WLC participants, distress was not associated with cognitive change. Findings underscore the importance of tailoring psychosocial interventions to address age-related stressors and cognitive health in breast cancer survivors.</p
Engagement with a Cognitive Behavioral Stress Management Website: Assessment of a Waitlist-Controlled Trial among Women with Breast Cancer
No full textAmong existing telehealth interventions, cognitive behavioral stress management (CBSM) offers particular benefit for reducing psychosocial suffering and promoting disease adaptation, particularly among patients with cancer. Among patients with breast cancer, CBSM has been adapted and tested in person, and while efficacious, many barriers stand in the way of in-person treatments for cancer survivorship. CBSM has been tested via telehealth for patients with breast and prostate cancer, which may offer an alternative and accessible method for intervention delivery.This trial delivered synchronous, 10-week videoconferenced CBSM plus access to an asynchronous website to women with nonmetastatic breast cancer. In the current dissertation, three studies were conducted to examine predictors and outcomes of engagement.The first study tested patient-level characteristics, including sociodemographic, medical, geographic, and psychosocial characteristics on program engagement with CBSM. No patient-level predictors impacted program-level engagement. The second study determined the effects of therapist adherence and competence in videoconferenced sessions on weekly participant engagement. Few patient-level covariates, including receipt of adjuvant treatment, predicted engagement over and above other predictors. Lastly, no effects of therapist behaviors, patient engagement, or the combination of these effects on patient post-intervention outcomes (i.e., negative and positive affect, fatigue, pain, depressive and intrusive symptoms, and sleep disturbance) emerged. Patient-level factors, including days since surgery and pre-CBSM outcome values predicted post-CBSM outcomes over therapist behaviors and engagement.Overall, findings point to the potential for treatment-related factors to impact engagement and uptake of asynchronous digital interventions. Future directions include expansion of engagement measurement modeling and modifications of asynchronous interventions to encourage engagement through human centered design.</p
Effects of Neighborhood Environment on Child Behavioral Health
No full textExternalizing behaviors in childhood is a major developmental, clinical, and societal concern that have become one of the most prevalent issues in children and youth mental and behavioral health as well as one of the most common reasons for which families seek treatment. Neighborhood environment is an emerging area of research that has implications with children’s physical, emotional, and psychological well-being, including externalizing behaviors. While externalizing behaviors have been extensively studied, there persists gaps in the literature addressing the larger societal influences—including neighborhood environment—that are associated with externalizing behaviors, especially in early childhood (1.5 – 6 years). This dissertation study’s purpose will be to: (1) evaluate the current state of the science linking neighborhood collective efficacy to child externalizing behaviors across developmental trajectories, (2) examine neighborhood-level childhood opportunity and its association with externalizing behaviors in early childhood, and (3) explore whether parenting mediates the relationship between neighborhood-level childhood opportunity and externalizing behaviors in early childhood. Employing quantitative approaches, this dissertation study aims to understand neighborhood environment as a potent social determinant of health to address externalizing behaviors in the context of neighborhoods with shared characteristics of strengths and vulnerabilities.</p
Tail Wags Dog: Influence of "Solubilizing Tails" on the Binding Affinities of Photoswitchable Kinase Inhibitors
No full textMore than 70% of all human proteins are phosphorylated by protein kinases revealed in the human kinome, highlighting their relevance as they modulate the activity, localization, and binding partners of target substrates. In particular, phosphorylation of the epidermal growth factor receptor (EGFR) relates it to cellular survival, proliferation, and development. Such a diverse role implicates their involvement in tumorigenesis and cancer progression which calls for the development of proficient EGFR inhibitors. Recent studies hint toward activity external to its ATP binding site that somehow increases the binding affinity of those particular kinase inhibitors – a region not thoroughly explored.In response, we have developed photoswitchable derivatives containing similar motifs with the addition of solubilizing moieties. Unique to these potential EGFR inhibitors, is their ability to reversibly isomerize between trans and cis conformations upon ultra-violet and visible light exposure, enabling the assessment of external interactions that aid in binding to the receptor’s ATP pocket. In this work, the design, synthesis, and photophysical properties of a new generation of EGFR probes are reported, along with the optimal conditions of isomerization amidst competing mechanisms and the kinetics of both the forward and reverse processes. These findings will help in the development of more potent and selective small-molecule kinase inhibitors.</p
Stuck Between an Inflexible Heart and Mind: Examining Heart Rate Variability, Cognitive and Emotion Flexibility in Relation to Internalizing Symptoms
No full textIndividuals with internalizing disorders (e.g., anxiety, depression) often exhibit difficulties with cognitive and emotion flexibility. Cognitive flexibility is an important control mechanism for adapting human thought and action, while emotion flexibility enables regulation of emotional perception and reactions. Laboratory-based tasks involving cued flexible thinking do not adequately capture an individual’s ability to adapt to environmental changes without guidance or represent the extent to which individuals must exert flexibility in daily life. Thus, researchers need to examine more ecologically valid measures of flexibility in relation to symptoms of internalizing disorders. We developed a novel item-generation task to assess how individuals flexibly generated thoughts within and across cognitive and emotional domains. While flexibility with cognitions and emotions is important for effective adaptation to environmental changes, heart rate variability (HRV), the fluctuations in the time between heart beats, provides a non-invasive measure of autonomic nervous system functioning in response to stressors, both in the laboratory as well as with wearable devices. Using an unselected sample of undergraduate students (n=110, 18-22 years old, 58 % female), we characterized how cognitive and emotion flexibility uniquely relate to clinical symptoms of anxiety. In addition, we characterized both lab-based and ambulatory measures of vagally-mediated HRV in relation to cognitive and emotion flexibility using the novel item-generation. Overall, results indicate that performance on the item-generation task was related to standardized measures of cognitive flexibility. While HRV during the task was not related to performance, higher HRV during a control task prior to item-generation predicted better performance across most trial types. Finally, performance was also related to self-report symptoms of anxiety, although this relationship was more robust in dual category conditions. Limitations and clinical implications of the findings are discussed.</p
Molecular Mechanisms and Polyunsaturated Fatty Acid Sensitivity of Cardiac Ion Channels
No full textThe cardiac action potential is generated by sodium and calcium channels, which depolarize the membrane, and potassium channels that repolarize the membrane. Loss of function of potassium channels hERG and KCNQ1/KCNE1, which generate IKr and IKs currents, are the most common cause of Long QT Syndrome (LQTS). LQTS is an arrhythmia disorder predisposing individuals to ventricular fibrillation and sudden cardiac death, characterized by delayed repolarization and prolonged QT interval. Some polyunsaturated fatty acid (PUFA) analogs are KCNQ1/KCNE1 activators that could reduce QT interval and lessen LQTS risks. To understand PUFA analog effects on hERG channels, I tested DHA-glycine and LIN-glycine on Xenopus oocytes expressing hERG channels, showing these PUFAs do not affect hERG channel activation, inactivation or recovery. We evaluated the arrhythmia-associated mutation R231C in KCNQ1/KCNE1 channels, measuring voltage sensor movement and ion permeability in oocytes expressing WT and R231C-mutated channels. We propose S4 is in the intermediate-activated state in both KCNQ1 R231C and KCNQ1/KCNE1 R231C channels. Finally, this project investigates structural details of KCNE1-induced rearrangements when the modulatory subunit binds KCNQ1. We mutated residue K285 on the S5-P loop and examined mutation effects on channel sensitivity to PUFA analogs with and without KCNE1 using Two-Electrode Voltage Clamp electrophysiology. The mutation causes PUFA analogs to have different effects on conductance and voltage dependence in KCNQ1 alone versus KCNQ1/KCNE1 complex, suggesting the S5-P loop changes conformation when KCNE1 binds KCNQ1. Overall, this work aims to understand the complex pharmacological interactions between PUFA analogs and potassium cardiac ion channels, and also to investigate the role of mutations and KCNE1 in modulating channel function.</p
Electromagnetic System with Metastable Spatial-Temporal Considerations for Neural Stimulation and Recording
No full textThis dissertation presents an interdisciplinary study of wireless neural interfacing, leveraging a high spatial and temporal precision electromagnetic stimulation system for neural modulation. A novel magnetic stimulation system was designed and its feasibility validated via multiphysics modeling in COMSOL, which demonstrated that a high-frequency alternating magnetic field can induce suprathreshold electric fields in tissue to reliably evoke neural action potentials. Based on the modeling results, a custom high-frequency amplifier and air-core coil were developed and bench-tested, confirming the ability to deliver the required field strength for neural stimulation. Using an anesthetized rodent experiment, the system achieved successful in vivo peripheral nerve (sciatic) stimulation: the wireless magnetic stimulus elicited consistent neural responses, evidenced by reproducible limb motion and thereby validating contactless electromagnetic neural activation. In addition, theoretical work was undertaken to support future wireless neural recording using MENPs. This effort analyzed the magnetoelectric coupling at the neuron interface and introduced a proof-of-concept lock-in detection scheme, indicating that MENPs could function as wireless transducers for capturing neuronal signals. Overall, by bridging physics-based modeling, engineering design, and neuroscience experimentation, this work delivers a validated electromagnetic stimulation platform and establishes the foundation for next-generation, fully wireless brain–machine interfaces.</p
Applied Magnetics for Medical Devices from Magnetoelectric Nanoparticles to Macroscale Electromagnetic Devices
No full textMagnetoelectric nanoparticles (MENPs) are introduced as a platform for wireless medical intervention and neuromodulation. Magnetic methods avoid limitations of electrical stimulation in conductive tissues, where charge screening and attenuation restrict penetration and precision. By coupling magnetic and electric order, MENPs convert alternating magnetic fields into localized electric potentials at cell membranes, enabling deep signal penetration with external fields through the brain and body.We synthesize core-shell cobalt ferrite and barium titanate MENPs as a biocompatible composite material. The cobalt ferrite core supplies strong magnetostriction, while the barium titanate shell provides piezoelectric polarization and improves biocompatibility. Nanoscale dimensions support transport across biological barriers, notably the blood-brain barrier (BBB) and promote close contact with neurons to maximize the efficiency of the generated fields. We present fabrication, structural and functional characterization (crystallography, magnetic hysteresis, XRD, microscopy), and a multi-scale evaluation from primary neuronal cultures to rodent and non-human primate (NHP) models. Although synthesis remains under optimization, experiments show repeatable, wireless neural activation with externally applied magnetic fields, validating MENPs as nanoscale receivers for wireless localized neurostimulation. We also report preliminary studies indicating targeted ablation of cancer cells in mice via magnetoelectrically mediated mechanisms, suggesting minimally invasive oncology applications. Finally, we outline theory and device concepts for MENP-assisted neural recording, establishing benchmarks and design criteria for next-generation magnetoelectric brain-machine interfaces.</p
Sociodemographic Characteristics of Cancer Survivors Referred to Exercise Oncology Services: Who Follows Up?
No full textIntroduction: Healthcare providers are important for promoting positive health behavior changes in cancer survivors (CS) and well-positioned to refer to exercise physiologists. Analysis of referral habits using electronic medical record systems can help cancer centers understand and improve their referral pathways. The goal of this thesis was to understand sociodemographic characteristics of CS referred to exercise oncology (EO) support services. Methods: This study was a retrospective analysis between October 2019 - December 2023. Data was extracted from the University of Miami Health System’s systems through My Wellness Check Platform (MWCP) and EPIC (Electronic medical record system through the University of Miami) for a total sample of 1,847 CS. Descriptive statistics were used to describe frequencies (%) of referrals made to EO by the referral channels. Sociodemographic differences in CS who followed up vs did not follow up with EO services were examined using logistic regression. Statistical analyses were performed using SAS version 9.4 statistical software. Results: Of the 1,847 CS referred between October 2019-December 2023, 94% (n=1740) were referred through EPIC and 6% (n=107) from MWCP. The CS were primarily female (79%), non-Hispanic (50%), White (81%), English-speaking (75%), married (55%), insured (67%), and breast CS (52%). Forty-nine percent (n=906) followed up with EO services. Of the 107 CS referred from MWCP, 67% (n=72) followed up with EO services. Of the 1,740 CS referred from EPIC, 48% (n=834) followed up with EO services. CS who were ≥ 60 years old (vs < 60 years old; OR=1.33, 95% CI=1.08-1.63, p<0.05), Non-Hispanic (vs. Hispanic; OR=0.75, 95% CI= 0.61-0.92, p<0.05), and referred through the MWCP (vs. EPIC: OR=0.47, 95% CI=0.31-0.72, p<0.05) were more likely to follow up with EO services. Conclusions: Findings from this study provide a better understanding of referral follow up with EO services at a large, cancer center. Results suggest that EHR-integrated referral pathways may serve as important tools to increase reach to EO services
Molecular Encapsulation Enforces Selectivity on the Reactivity of Excited Organic Molecules
No full textSupramolecular photochemistry uses molecular encapsulation to control excited-state reactions with exceptional precision. Confinement within host cavities tunes reaction pathways, stabilizes reactive intermediates, and suppresses competing processes—enabling outcomes often inaccessible in bulk solution. This work explores the water-soluble host Octa Acid (OA) capsule as a nanoscale reactor that imposes structural and dynamical constraints on guests, directing their photochemistry. In water, β-ionyl derivatives above ~0.5–1 mM form nano-aggregates, competing with host binding. OA encapsulation overcomes this self-assembly and enables unique reactivity. The high-energy 7-cis-β-ionone is stabilized in OA, reaching ~40% yield after UV irradiation compared to ~10% in bulk, as confinement suppresses cyclization. Visible-light E→Z isomerization of β-ionyl derivatives becomes regioselective in OA, selectively targeting one alkene and stabilizing higher-energy Z-isomers. Unexpected triplet energy transfer between OA and anionic sensitizers reveals “like-charge attraction” effects in water. The OA capsule accelerates the “catalysis-resistant” dimerization of cyclopentadiene by >2000-fold via guest pre-organization and sequential turnover, demonstrating confinement-driven catalysis. For arylazoisoxazole molecular switches, OA encapsulation restricts mobility but maintains reversible E/Z isomerization. CH–π interactions and substituents shift photostationary equilibria and thermal reversion rates, tuning switching performance over many cycles without host dissociation. Overall, OA enables stabilization of fleeting species, precise control of selectivity, unexpected energy-transfer pathways, dramatic rate enhancements, and modulation of photoswitch behavior. These findings establish supramolecular encapsulation in water as a powerful strategy for designing precision photochemical systems and expand the conceptual toolkit for controlling light-driven processes in aqueous environments.</p