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MORPHOLOGICAL INVESTIGATION ON THE EFFECTS OF NETARSUDIL ON THE VOLUME OF GIANT VACUOLES IN SCHLEMM’S CANAL ENDOTHELIAL CELLS OF HUMAN EYES
(2025) Fritea, Nikolas Vaughn; Gong, Haiyan; Dominguez, M. Isabel
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, primarily due to its irreversible nature and its association with elevated intraocular pressure (IOP). The exact mechanisms by which outflow resistance is regulated remains difficult to identify. Aqueous outflow is not uniform, rather segmented into high-, low-, and non-flow areas. Lowering IOP is the only effective treatment for POAG. One newly approved class of drug that is currently used to lower IOP in POAG is netarsudil, a Rho kinase/norepinephrine transporter inhibitor. Previous studies conducted in the Gong lab showed that netarsudil increases outflow facility through trabecular meshwork expansion and episcleral vein dilation, leading to an increase in high-flow areas, consequently increasing outflow facility and lowering IOP. However, the effect of netarsudil on the inner wall endothelial cells of Schlemm’s canal has not been fully explored. Giant vacuoles (GVs) are a unique structure in the inner wall endothelium of Schlemm’s canal that play an important role in regulating aqueous outflow resistance via their I-pore formation. Previous studies have found that the size of GVs with I-pores is significantly larger than that of GVs without I-pores, suggesting that GV’s play a role in I-pore formation. This study aimed to test the hypothesis that netarsudil increases GV volume and percentage of GVs with basal opening and I-pores compared to control eyes. Two pairs of human donor eyes were perfused with netarsudil in one eye and vehicle solution in the other eye of each pair for 3 hours at constant pressure (15 mmHg). Two different colors of fluorescent tracer were perfused into the eye before and after netarsudil treatment to label flow pattern changes prior to perfusion-fixation. Tissue wedges from high-, low-, and non-flow areas, as well as newly-recruited high-flow or low-flow areas (identified by comparing green and red fluorescein tracer global imaging) were processed and imaged (~2000 images per wedge) using serial block face scanning electron microscopy. Three hundred GVs, with I-pores and without I-pores from four different flow regions of each eye, were identified and traced. The volumes of GVs across these groups were compared using RStudio.
Mean GV volume was significantly larger in netarsudil-treated eyes compared to control eyes overall (p < 0.01) and GVs with I-pores were significantly larger than GVs without I-pores (p < 0.05) in both groups. When analyzing different flow type areas, mean GV volume was significantly greater in treated high-flow areas than in control high- and non-flow areas (p < 0.01). Finally, mean GV volume was significantly larger in recruited-flow than control non-flow (p < 0.05). These findings suggest that one mechanism by which netarsudil lowers IOP may be its ability to increase GV size and the percentage of GVs with I-pores. Further study is needed to confirm whether netarsudil increases the number of GVs with I-pores as sample size increases and to determine whether netarsudil affects membrane thinning by measuring the thickness of the cellular membrane of GVs.
Examining and exploring motivating factors for parents to accept the HPV vaccine for themselves and for their age-eligible children against HPV at dental clinics – mixed methods approach
(2025) Fu, Daniel; Pierre Joseph, Natalie; Laird, Lance D.
Dental hygienists and dentists possess the knowledge, skills, and resources to screen patients for HPV and discuss preventive measures. Conversations between patients and their trusted dental care providers can create opportunities for patients to follow through with their HPV vaccination schedule or even begin the vaccination process. This thesis study aims to examine the factors that may influence parents to receive the HPV vaccine for themselves and for their children at dental clinics, while also identifying the most effective strategies for dental care providers to communicate with patients about HPV and vaccination. This study was done through a mixed methods approach that involved qualitative interviewing subjects who participated in a prior sub-study and have completed a quantitative survey from a parent clinical trial study. Although interviewed participants expressed mixed opinions on getting the HPV vaccine at a dental clinic for themselves and for their children, all agreed that HPV and vaccinations was an important topic to discuss with dentists. All interviewed parents expressed interest in discussing HPV and vaccination with their dental care providers, believing it would encourage patients to consider the vaccine for themselves and for their children. Participants also recommended that dental providers promote discussions between patients and primary care providers to boost HPV awareness and vaccine uptake.
Using the All of Us Research Program to identify novel risk factors for aortic aneurysms
(2025) Fullem, Patrick L.; Seta, Francesca
OBJECTIVE: Aortic aneurysms (AA) are some of the most serious and life-threatening cardiovascular diseases (CVD). Once a rupture or dissection of the aortic wall occurs, 50% of patients die before getting medical attention. Well-established risk factors include smoking, chronic high blood pressure, high cholesterol, and atherosclerosis. These are some of the most common chronic issues among the US population. While lifestyle and behavioral factors contribute to the risk of AA and other CVD, some genetic mutations also predispose people to higher risk of AA. Those who have Marfan syndrome, Ehlers-Danlos syndrome, and other connective tissue-related diseases are at higher risk for developing AA, mainly in the thoracic portion of the aorta. Understanding which genetic mutations, or SNPs, are associated with increased risk of AA can play a critical role in precision medicine to help those who are genetically predisposed manage this disease better and lower the risk of death through targeted therapies and potential early screenings and monitoring. The goal of this project was to use a recently established and publicly available human dataset from the All of Us Research Program to identify novel risk factors for abdominal and thoracic aneurysms. Specifically, we hypothesized that circulating glucose and cholesterol contribute to the development of AA, independently of being diabetic or having atherosclerosis.
METHODS: To test our hypothesis, I first extracted data from the All of Us (NIH) dataset; I then used logistic regressions to determine associations between low, medium, and high levels of glucose (Hemoglobin A1C) or cholesterol (total, HDL, LDL and LDL/HDL ratio) and AA. The analyses were run separately for thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) as these forms of AA are generally considered to have different pathogenesis with TAA being genetically affected, whereas AAA is linked mainly to lifestyle factors.
RESULTS: Prediabetic A1C levels were associated with increased odds of having AAA (OR=1.15, 95% CI [1.01,1.30], p=0.0333) after adjusting for race, ethnicity, gender/sex, and age. On the contrary, after adjusting for the same demographic variables, higher A1C levels were associated with decreased odds of having TAA for both Prediabetics (OR=0.85, 95% CI [0.76, 0.95], p=0.0058) and Diabetics (OR=0.56, 95% CI [0.48, 0.66], p<0.0001). Similarly, slightly elevated (At-Risk) total cholesterol levels were associated with decreased odds of having AAA (OR=0.65, 95% CI [0.44, 0.96], p=0.0303) after adjusting for race, ethnicity, gender/sex, and age. Using the same controlled variables, both At-Risk (OR=0.77, 95% CI [0.765, 0.774], p<0.0001) and High (OR=0.73, 95% CI [0.725, 0.740], p<0.0001) total cholesterol levels were associated with decreased odds of having TAA. After controlling for race, ethnicity, gender/sex, and age, lower levels of HDL, a form of cholesterol considered protective for CVD, were associated with increased odds of having AAA (At-Risk: OR=1.27, 95% CI [1.02, 1.60], p=0.0363; Low: OR=1.50, 95% CI [1.23, 1.84], p<0.0001). Moreover, increased levels of LDL, also known as “bad” cholesterol, were associated with decreased odds of having TAA, after controlling for race, gender/sex, ethnicity, and age (At-Risk: OR=0.79, 95% CI [0.787, 0.798], p<0.0001; High: OR=0.57, 95% CI [0.56, 0.58], p<0.0001). A higher LDL/HDL ratio was associated with decreased odds of having TAA (OR=0.852, 95% CI [0.851, 0.853], p<0.0001).
CONCLUSION: The results suggest that circulating glucose may have a protective effect against TAA but a detrimental effect for AAA. Higher HDL cholesterol levels may also provide a protective effect against AAA, while increased total and LDL cholesterol seem to have a protective affect against TAA, along with a larger LDL/HDL ratio. Future analyses, however, should control for medication usage, specifically for anti-diabetic and cholesterol-lowering medications, in order to fully understand the association between circulating glucose or cholesterol and AA.
Assessing the impact of a diverting ostomy on the quality of life, emotional health, and psychosocial functioning in children with IBD and their families
(2025) Gibson, Grace; Morera, Claudio; Rufo, Paul A.
BACKGROUND: Inflammatory Bowel Disease (IBD) is an overarching term for multiple chronic conditions defined by inflammation of the gastrointestinal tract. These are typically diagnosed in young adulthood or adolescence, with an increasing incidence rate in pediatric populations. In cases of severe IBD that are not well managed with initial treatments, surgical therapy may be indicated to pursue placement of temporary or permanent ostomy. Undergoing ostomy procedures greatly impact patients with IBD and their families financially and affect their quality of life, self-esteem, and day-to-day interactions. Our study aims to assess the impacts of a diverting ostomy on the quality of life, emotional health, and psychosocial functioning of pediatric patients with IBD and their families. Parent and family HRQOL describes the addition of caregiving tasks that come with managing chronic IBD. Psychosocial functioning refers to patients and their parents’ levels of anxiety or depression. METHODS: Pediatric patients with diagnosed IBD who are scheduled to undergo a diverting ileostomy or colostomy were recruited alongside their parents from Boston Children’s Hospital (BCH). Multiple questionnaires were administered to both patient and their parents at baseline and two subsequent follow-ups at 2-3 months post-operation and 9-12 months post-operation. Participating children completed questionnaires regarding health-related quality of life (IMPACT), anxiety (SCARED), depression (PHQ-9), and other psychosocial functioning (FDI and OAS-23). Participating parents then completed additional questionnaires regarding parental stress and psychosocial functioning (PIP) and anxiety (GAD-7). DISCUSSION: Symptoms and treatment related to a child’s diagnosis of IBD greatly impact their quality of life, with now the added effort required for ostomy management. Providing in-depth training and mentoring on ostomy management can increase patients' knowledge and confidence. Our study hypothesizes a positive correlation between postoperative time and a child's quality of life, with a gradual improvement in QoL over time. Chronic IBD has also been associated with an increased risk of anxiety and depression. Additionally, undergoing extensive surgery with multiple reported symptoms such as pouch leakage, odor, or skin irritation will have a high likelihood of impacting psychosocial functioning. Our study hypothesizes that there may be increased anxiety and depression symptoms immediately following surgery but that these will dissipate with time. Providing adequate and structured ostomy care may facilitate decreased feelings of anxiety. Our study anticipates that their child’s ostomy procedure will greatly impact parental stress. Wehypothesize that parental anxiety and depression may increase following surgery but could plateau as time increases. Similarly to parenting stress, gaining more knowledge about ostomy procedures and management may decrease parental anxiety. Additionally, this would heavily rely on their child’s psychosocial functioning about their diagnosis and ostomy procedure.
A review of contributing factors in the development and maintenance of eating disorders
(2025) Gigliotti, Hannah; Navalta, Carryl P.; Bragdon, Beth
Eating disorders are mental health conditions that can profoundly disrupt an individual’s life with the potential to cause serious harm. Numerous factors can influence the diagnosis of an eating disorder, making it difficult to maintain control over the condition. The fundamental information about eating disorders and their primary contributing factors was analyzed to understand the main reasons for eating disorder occurrence and determine effective methods of treatment. The primary method utilized to evaluate the extensive topic of eating disorders was a literature review. Eating disorders have been researched for years since their recognition as a mental health problem. Various literature articles support the reality of having a frequent combination of factors in the development and maintenance of an eating disorder. However, the most influential causes of the onset of eating disorders were determined to be genetic correlation and parental involvement. The impact of parental involvement is established through the environment. Genetics are viewed as a primary factor because they are recognized as being uncontrollable with preexisting tendencies. The environmental impact is correlated with many other factors to support its potential for immense effects. The best form of treatment that targets the core development of eating disorders and promotes the essential technique for successful life maintenance is family-based treatment. The research should continue to be conducted to acquire more knowledge about the impact of eating disorders so we can lower incidence rates and overall frequency of diagnosis.
Improving behavioral health crisis management in emergency departments: exploring community-based approaches and internal operational strategies
(2025) Grigorova, Yoana; Soghomonian, Jean-Jacques; O'Connor, Patrick
Emergency department (ED) operations range from managing acute medical patients to serving as a safety net for primary and specialty care needs. The growing demand for behavioral health (BH) services has placed additional pressure on EDs, where challenges such as limited resources, noisy and restrictive environments, and long wait times often result in suboptimal care for BH patients. Multidisciplinary, patient-centered BH care has been shown to improve treatment outcomes. Beyond medical interventions, many BH patients require social support and connections to welfare services to ensure long-term stability. This review examines existing community-based BH service models in the United States and internationally, presenting viable alternatives to ED treatment. Though these models vary in their specific goals, many have been successful in reducing the need for in-hospital interventions for individuals struggling with BH. Accessibility to these services is critical for their effectiveness, enabling BH patients to receive timely and appropriate care outside of emergency settings. Changes to ED structure and protocols are also explored, focusing on practices that have improved BH care delivery. By providing a comprehensive overview of strategies, this thesis highlights potential solutions that could optimize the role of EDs and enhance the overall care quality for BH patients.
Neurodevelopmental and mental health outcomes in preterm infants: effects of exposures to opioid analgesic, anesthetic and sedative agents
(2025) Gomez, Isabella; Trinkaus-Randall, Vickery; Jackson, Shawn
BACKGROUND: Preterm infants are routinely exposed to various classes of analgesic, sedative, and anesthetic agents. Several pre-clinical studies on rodents and nonhuman primates have demonstrated that exposure to sedative and anesthetic agents is associated with neurotoxicity in the developing brain. In 2016, the United States Food and Drug Administration announced, in a black box warning, that “repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains,” suggesting that these medications should be administered with caution. However, further research must be conducted to thoroughly comprehend how, or if, anesthetic exposure during early life affects human brain development. Infants (particularly pre-term infants), children with chronic medical conditions, and children with acute critical illnesses are thought to be particularly at risk for neurotoxicity. Understanding the variability in opioid analgesic, sedative, and anesthetic agents used in the neonatal intensive care unit (NICU) as site-to-site variation will provide key information on exposure risk and is a critical initial step to better understand neurodevelopmental outcomes in this vulnerable population.
OBJECTIVE: To characterize the trends in types of drugs, drug dose, duration, and co-exposure to opioid analgesic, sedative, and anesthetic agents of preterm infants from 2010 to 2023 at Boston Children’s Hospital.
METHODS: The initial phase of the study, described in this thesis, is to retrospectively analyze sedation practices at Boston Children’s Hospital in pre-term infants. The proposed retrospective cohort study design will involve comprehensive data collection with respect to analgesic and sedative drug exposures in preterm infants of various institutions from Boston Children’s Hospital (BCH), including three cohorts: NICU Preterm Cohort, Surgical Preterm Cohort, and Preterm Birth Cohort.
RESULTS: The result of this study provides key information regarding drug exposure in preterm infants. The drugs analyzed in this study are characterized by classes: opioid analgesics (MME/kg), benzodiazepines (LME/kg), intravenous anesthetics or sedatives (including propofol, ketamine, and dexmedetomidine), neuromuscular blocking agents, and other agents. We were able to assess trends in drug management of preterm infants at BCH from 2007 to 2023 between the NICU and Surgical Preterm Cohorts (n=686). The Surgical Preterm Cohort had a significantly higher frequency of drug exposures across all three drug classes (opioid analgesics, benzodiazepines, intravenous anesthetics/sedative agents), with higher average doses and increased variability within the cohort compared to the NICU Preterm Cohort (p < 0.05). Length of admission highly impacted drug exposure (p < 0.001), indicating that longer hospitalizations are associated with increased analgesic, sedative, and anesthetic agent exposures. An analysis of trends over time showed that there was a strong association between opioid drug exposure and year of admission (p < 0.05), but further evaluation of these values did not indicate a clear association over time. The use of benzodiazepines and intravenous anesthetics/sedatives did not show significant variations over time (p > 0.05).
CONCLUSIONS: The Surgical Preterm Cohort received significantly higher opioid analgesic, sedative, and anesthetic agent exposures, with length of admission being the most significant determinant of opioid and benzodiazepine exposure. Temporal trends (2007-2016) in opioid exposure may suggest some changes in clinical management over time, while benzodiazepine and intravenous anesthetic/sedative agent management remained stable over the years. This study provides important information regarding drug exposures of preterm infants, highlighting the effects of surgical interventions, length of hospitalizations, and clinical management practices on drug exposures. Future studies will build upon this data to better characterize the comparability of clinical sites and NICU levels, as well as the demographic and clinical characteristics of patients receiving care at these institutions.
The effect of superglue fuming with PolyCyano UV powder on touch DNA from fingerprints
(2025) Goodspeed, Elise Marie; Cotton, Robin W.
One-step fluorescent cyanoacrylate fuming products like PolyCyano UV powder decrease the amount of time required to process latent fingerprints. The effects of these products on downstream DNA analysis are an important avenue of research to help determine which latent print processing method is right for specific case work. There is not a consensus on what, if any, effect PolyCyano UV has on the amount of DNA yield or the degradation of touch DNA samples. This study aimed to evaluate the effects of the PolyCyano UV on prints from four adjacent fingerprints from 30 donors deposited onto glass slides. The amount of small autosomal DNA, the percent increase or decrease in DNA yield, and the degradation index (DI) were measured across the donors using PCR. Three donor sets were taken through to profile to determine if peak heights were affected. There was no statistically significant difference in the amount of DNA yielded after PolyCyano UV fuming, nor the percent increase or decrease in DNA yield of those that did show a change in yield. The DIs of the samples fumed with PolyCyano UV were statistically lower than those samples left untreated. Two of the profiled donors had PolyCyano UV fumed samples with peak heights that were statistically greater than those that were not fumed. One of the profiled donors had the opposite.
In vivo identification of drug therapeutics for nemaline myopathy
(2025) Gill, Sehajpreet; Gerstenfeld, Louis; Gupta, Vandana
This study employs the DiscoveryProbeTM FDA-approved drug library to perform a small molecule high-throughput drug screen as a strategy for developing therapies for Nemaline Myopathy (NM). Nemaline myopathy is a rare congenital neuromuscular disorder characterized by muscle weakness and the accumulation of fine rod-like structures, known as nemaline bodies, within skeletal muscle fibers. The main objective of this study was to identify potential therapeutic compounds capable of alleviating the pathological features of NM using a klhl41b-/- zebrafish model, a well-established representation of human NM pathology. 1320 FDA-approved drugs were screened using a novel drug repurposing strategy on the klhl41b-/- zebrafish model, an ortholog sharing 80% similarity with KLHL41. Core methodologies included weekly drug screening cycles which involved breeding and genotyping zebrafish lines, conducting behavioral assays with automated activity monitor to assess locomotor function, statistical analysis of the data using GraphPad Prism, and secondary validation screens to confirm drug efficacy. The preliminary screen identified 56 compounds that significantly improved the swimming behavior in the klhl41b zebrafish model, 830 compounds that showed no significance, 161 compounds that resulted in a reduction in swimming behavior, and 273 that displayed toxicity. These 56 compounds improving swimming were further analyzed to uncover common molecular pathways, revealing key mechanisms of action including adrenergic receptors, cholinergic receptors, histamine receptors, G-protein coupled receptors/ion channels, nuclear receptors, tyrosine kinase receptors, and other non-receptor enzyme inhibitors. To test the efficacy of these compounds in a mammalian system, selected candidates will be further screened in Klhl41 mutant C2C12 myoblast cells, bridging the gap between zebrafish models and mammalian systems. This study highlights the effectiveness of a small molecule high-throughput drug screening approach in identifying promising therapeutics for NM. It lays the groundwork for advancing these candidates toward clinical applications.
How long do I have to be strong? The exploration of endometriosis in Black women: efficacy and implications of aromatase inhibitors as a novel treatment
(2025) Greenidge, Masara Amali; Pam, LaKedra; Ajayi-Lowo, Esther O.
Endometriosis is a complex gynecological ailment that affects millions of women worldwide. However, within the discourse on endometriosis, there exists a notable gap concerning its impact on Black women. The Strong Black woman can be seen as a philosophical notion that encourages Black women to “rise above” their intersectional vulnerabilities. Often intended as an empowering compliment, the strong black superwoman cultural trope has progressively caused many African American women to have internalized mental and physical health problems. Moreover, black women who experience endometriosis experience difficulties in the diagnosis and treatment in said group. This thesis aims to investigate the efficacy and implications of using aromatase inhibitors as a novel form of treatment for endometriosis in Black women. This literature analysis hopes not only to inform those about the disease but hopes to also shed light on the often-ignored experiences of Black women with endometriosis. All while exploring the advantages and disadvantages of using Aromatase Inhibitors to manage.