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Breaking Silence, Bearing Consequences: Male Patients' Retrospective Narratives of Clinician-Perpetrated Sexual Abuse
No full textBackground: Sexual misconduct by health care clinicians is a type of sexual abuse with significant consequences for patients, although there is limited literature examining the experience of male survivors.
Aim: To examine the effects of sexual misconduct experienced by male patients during young adulthood by the same healthcare clinician.
Methods: Using BERTopic modeling, a machine learning-based topic modeling method, we analyzed the narratives from records in a class-action lawsuit involving men aged 18-22 at the time of the abuse, who provided narratives years later that included reflections on their experiences over time.
Results: Three themes were described by the men: "Violation of Trust in Clinical Settings," "Breaking Silence Through Public Disclosure," and "Long-term Psychological and Relational Consequences."
Conclusion: There is an enduring psychological impact of clinician sexual misconduct on male survivors, and a subsequent need for trauma-informed, gender-sensitive forensic nursing care in every patient encounter.No embarg
Exploration of IRS2 as a Therapeutic Target in Breast Cancer
No full textBreast cancer is one of the leading causes of cancer death in women worldwide. Dysregulation of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway, a crucial signaling axis necessary for regulating normal organismal growth and metabolism, promotes many aspects of breast cancer progression. Insulin receptor substrate (IRS) proteins are enzymatically inactive, cytoplasmic adaptors that act downstream of insulin receptor (IR) and IGF-1 receptor (IGF-1R) activation. Previous studies have shown that IRS2, rather than its homologous family member IRS1, enhances tumor invasion, survival, and metastasis. IRS2 represents an unexplored therapeutic target that, if inhibited, could provide clinical benefit for individuals with aggressive tumors. Development of an efficacious therapy that inhibits IRS2 requires a thorough understanding of the mechanisms by which IRS2 mediates tumor progression and must overcome challenges in inhibiting cytoplasmic proteins that lack enzymatic activity. Thus, the focus of this thesis was to 1) determine the molecular basis by which IRS2 promotes tumor cell invasion, a hallmark of breast cancer, and to 2) test the in vivo efficacy of silencing IRS2 expression as a therapeutic approach to inhibit breast cancer progression.
I investigated how the ability of IRS2 to recruit phosphatidylinositol-3 kinase (PI3K) and the IRS2 C-terminus contributed to breast cancer invasion using in vitro models of breast cancer migration and invasion. I found that the IRS2-PI3K interactions and the IRS2 C-terminus enhanced epithelial-to-mesenchymal transition (EMT) and chemotaxis, two key processes that enable tumor cell invasion. PI3K recruitment, but not the C-terminus, was also needed to suppress random migration, suggesting dynamic regulation of IRS2-dependent cell migration. IRS2 promotes the formation of actin-based protrusions and the phosphorylation of key actin regulatory proteins after IIS pathway activation, providing mechanistic evidence for the role of IRS2 in regulating cell motility. Collectively, these findings give novel insight into IRS2 functions in breast cancer invasion.
Using a syngeneic model of triple negative breast cancer (TNBC), I showed that downregulating IRS2 expression using fully chemically modified small interfering RNAs (siRNA) reduced mammary tumor growth without causing hyperglycemia. I designed and validated siRNAs that selectively silenced IRS2, but not IRS1, in vitro in breast carcinoma cell lines and in vivo in mice. I then systematically identified optimal siRNA chemical modifications and administration route for robust mammary tumor delivery, finding that subcutaneous administration of siRNA conjugated to an albumin-binding dendrimer structure leads to robust delivery to both neoplastic cells and stromal/immune cell populations within primary tumors. Suppression of Irs2 mRNA expression in mammary tumors reduced vimentin expression in primary tumor cells, tumor vascularization, and frequency of M2-like tumor-associated macrophages, suggesting that siRNA treatment modulated tumor cell-intrinsic and -extrinsic processes. Together, these results support the feasibility of using therapeutic siRNAs to target IRS2 in vivo and provide rationale for the development IRS2-targeting therapeutics for the treatment of breast cancer.MD/PhD2 years2027-05-0
Threading the diagnosis: A case of the "string of pearls" sign in fibromuscular dysplasia
No full textNo embarg
Healthy at Home for COPD: An Integrated Digital Monitoring, Treatment, and Pulmonary Rehabilitation Intervention
Full text linkBackground: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality in the United States. Frequent exacerbations result in higher use of emergency services and hospitalizations, leading to poor patient outcomes and high costs. The objective of this study is to demonstrate the feasibility of a multimodal, community-based intervention in treating acute COPD exacerbations.
Results: Over 18 months, 1,333 patients were approached and 100 (7.5%) were enrolled (mean age 66, 52% female). Ninety-six participants (96%) remained in the study for the full enrollment period. Fifty-five (55%) participated in tele-pulmonary-rehabilitation. Participants wore the smartwatch for a median of 114 days (IQR 30-210) and 18.9 hours/day (IQR16-20) resulting in a median of 1034 minutes/day (IQR 939-1133). The rate at which participants completed scheduled survey instruments ranged from 78-93%. Nearly all participants (85%) performed COPD ecological momentary assessment at least once with a median of 4.85 recordings during study participation. On average, a 2.48-point improvement (p=0.03) in COPD Assessment Test Score was observed from baseline to study completion. The adherence and symptom improvement metrics were not associated with baseline patient activation measures.
Conclusions: A multimodal intervention combining preventative care, symptom and biometric monitoring, and MIH services was feasible in adults living with COPD. Participants demonstrated high protocol fidelity and engagement and reported improved quality of life.No embarg
Mycobacterial Homopolymeric Phase Variation as a Means of Rapid Adaptation
Full text linkMycobacterium tuberculosis stands out among many bacterial pathogens in that it does not acquire new genetic material via horizontal gene transfer, yet in spite of this evident handicap, the tubercule bacillus kills more people worldwide than any other infectious agent and has proven itself remarkably proficient in adapting to rapidly changing environmental pressures. Phase variable simple sequence repeats known as genetic homopolymers have emerged as a possible mechanistic solution to this apparent paradox. To further explore the role of mycobacterial genetic homopolymers, I first developed an experimental system to measure the frameshifting rate of mycobacterial homopolymers, and showed that homopolymeric repeats exhibit elevated mutation rates across mycobacterial species and diverse isolates. Next, after identifying multiple clinically prevalent homopolymeric phase variants in regions associated with the virulence determining ESX-1 Type VII secretion system, I engineered these variants into our lab-adapted Mycobacterium tuberculosis H37Rv strain and demonstrated that these positively selected polymorphisms can impact gene expression, protein secretion, drug sensitivity, and host-pathogen interactions. Taken together, these data support the hypothesis that Mycobacterium tuberculosis uses homopolymer-mediated phase variation to strategically direct genetic variation to certain genomic loci in order to adapt to the wide variety of conditions the pathogen may face throughout its infectious cycle, and that the consequences of such variation may have clinically relevant implications.Biochemistry and Molecular Biotechnology6 months2025-07-3
The association between multimorbidity and food insecurity among US parents, guardians, and caregivers
No full textBackground: Multimorbidity among parents, guardians, and caregivers may increase the risk of household food insecurity, which would negatively impact both parents and children. However, limited research has been done to evaluate this relationship among this population. To fill this gap, we examined the association between multimorbidity and food insecurity among U.S. parents.
Methods: Cross-sectional data from 2019 to 2022 of the National Health Interview Survey were analyzed. Parents, guardians, and caregivers with complete data (N = 26,579) were included. Multimorbidity is defined as having 2 or more conditions. In this study, multimorbidity was categorized as 2 or 3 + conditions from a sum of 11 chronic conditions: hypertension, hyperlipidemia, diabetes, arthritis, stroke, cancer, asthma, depression, anxiety, chronic obstructive pulmonary disease, and heart disease. The presence of food insecurity was defined in four nominal categories (secure, marginal food security, low food security, very low food security). Survey-weighted multinomial regression was used to assess the association of multimorbidity with food insecurity categories, controlling for sociodemographic characteristics. The association between physical versus physical-mental comorbidities and food insecurity was also analyzed.
Results: The mean study sample age was 38.8 years, 51% were women and 53% were non-Hispanic White race/ethnicity. Nearly half (49%) had ≥ 1 chronic condition; 23% had 1, 14% had 2, and 13% had 3+. The most common pair of chronic conditions among parents was depression and anxiety, and most common triad was depression, anxiety, and hypertension. After controlling for potential confounders, we found that parents with 3 + conditions had a higher risk of marginal (OR 1.75, 95% CI 1.47-2.10), low (OR 2.20, 95% CI 1.75-2.75), and very low food security (OR 4.1, 95% CI 3.2-5.2) compared to parents with no conditions. Differences were seen in the odds of food insecurity among parents with mental and physical conditions, as opposed to physical comorbidities alone.
Conclusions: Our findings suggest a higher risk of food insecurity in parents with multimorbidity. Parents with multimorbidity (especially those with comorbid depression and anxiety disorders) may be a key population to identify and intervene on food insecurity to improve health and well-being among US families.No embarg
Social Determinants, Mental Well-Being, and Disrupted Life Transitions Among Young Adults with Disabling Mental Health Conditions
No full textThis study sought to understand how young adults (age 18-25) with histories of mental health disorders are coping with disrupted transitions to adulthood during the COVID-19 pandemic. A cross-sectional web survey was conducted in March-June 2021 of 967 US young adults with pre-pandemic psychiatric disability to assess their current psychiatric status, interrupted transitions, and associations with social determinants including income, community participation, and social context. Mental health was assessed with the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and PTSD Checklist-Civilian Version. Social determinants were identified with the Epidemic-Pandemic Impacts Inventory. Interrupted transitions were measured with the Young Adult Disrupted Transitions Assessment. Multivariable logistic regression models predicted four types of transition disruptions and associations with current mental health, social determinants, and demographic factors. Disruptions were reported by 81.1% including interrupted education completion (38.3%), employment careers (37.6%), residential independence (27.7%), and intimate partner relationships (22.9%). Many screened positive for major depressive disorder (81.7%), PTSD (85.5%), or GAD (58.6%). Disruption in establishing intimate partner relationships was associated with depression, anxiety, and PTSD. Interrupted residential independence was associated with anxiety. Interrupted education completion was associated with PTSD. Interrupted employment was associated with anxiety. Social determinants significant in these models included social connections, community participation, income, and racial/ethnic identification. Results illuminate ways that current mental health and social determinants affect transition interruptions during the pandemic. Findings suggest the need for interdisciplinary approaches, integrated models of care, and assistance accessing treatment, rehabilitation, and community support services from adult service systems.No embarg
Intent to Test for COVID-19 in the Postpandemic Era
Full text linkThis cross-sectional study used an online national survey to examine the intent to test when COVID-19 was suspected among adults in the US between October 2024 and April 2025No embarg
Modeling Neisseria meningitidis transmission dynamics and the impact of pentavalent vaccination targeting serogroups A, C, W-135, Y, and X in the African meningitis belt
Full text linkThe African meningitis belt (AMB) faces recurring epidemics of (Nm) (a bacterium that causes meningococcal meningitis), posing significant public health challenges. This study develops a Susceptible-Carrier-Infected-Recovered (SCIR)-based dynamic model to investigate Nm transmission dynamics in the AMB region, focussing on the impact of pentavalent meningococcal conjugate vaccines targeting serogroups A, C, W-135, Y, and X. By incoporating vaccination strategies into the model, we provide a comprehensive framework for evaluating vaccine effectiveness and informing outbreak prevention and control efforts. Our model stratifies the population into high-risk individuals (ages 1-29 years), who are the primary targets of vaccination campaigns, and low-risk individuals (all other age groups), capturing differences in susceptibility and vaccine coverage. Our results reveal that the introduction of pentavalent vaccines significantly reduces the prevalence of carriers, particularly among high-risk groups, thereby curbing transmission and mitigating epidemic risks across the AMB region. Key epidemiological parameters, including reproduction numbers ( ), are derived to support targeted intervention strategies. Further analysis highlights the role of vaccination in lowering Nm transmissibility, especially in densely populated settings where close contact accelerates spread. Moreover, potential drivers of Nm outbreaks, including climate variability, socioeconomic disparities, and population density, are identified, highlighting the need for integrated public health intervention strategies. Further simulations also reveal the effectiveness of pentavalent vaccination among high-risk populations; however, further research is urgently needed to understand disease heterogeneity and vulnerability, particularly in young children and underserved communities. Thus, this study contribute to advancing our understanding of effective and sustainable vaccination strategies and enhancing epidemic preparedness in meningitis-endemic regions.No embarg
Impact of ALS-linked Mutations on the Structure and Dynamics of Profilin-1
No full textDysregulation of proteins involved in the formation and maintenance of the actin cytoskeleton has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the actin-binding protein, profilin-1 (PFN1), have been identified and linked to familial ALS. PFN1 is an essential protein that regulates different cellular processes, including membrane trafficking, neurite outgrowth, axonal development, neuronal growth cone formation, and GTPase signaling. Recent studies have shown that different ALS-linked PFN1 mutations can lead to either a gain or loss of function, depending on the stability of the mutant and its propensity for aggregation. In this thesis, I focused on two ALS-linked variants- G118V and M114T which exhibit a gain of function in formin-mediated actin dynamics.
To understand the biophysical differences between these two mutants and WT PFN1, I investigated how these mutations impact PFN1 binding affinity to its ligands using fluorescence and NMR spectroscopic methods. Reduced chemical shift perturbations observed in the β-strand containing the mutation site in M114T PFN1, compared to WT PFN1 suggest that the mutation impacts allosteric communication. In addition, I characterized the effects of the M114T mutation on PFN1 dynamics across fast and slow time scales. This dissertation represents the first study to examine conformational dynamics changes in ALS-linked PFN1 variants, providing insights into their functional impact and elucidating the role of cytoskeletal perturbation in disease.Biochemistry and Molecular Biotechnology2 years2027-05-2