Every spring the Graduate School Association sponsors a research symposium to present graduate research work to the VCU and local Richmond community. The event is an excellent opportunity for graduate students to present their original research and creative projects in a professional but relaxed environment. This is the only opportunity for many graduate students to showcase their work at VCU. Participation in this event has nearly doubled every year and attracts not only VCU students and faculty, but local media, legislators, and respected members of the Richmond business community.
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Mapping the VCU Campus Food Environment
Heather N. King, John C. Jones, and Dan J. Albrecht-Mallinger
Preliminary research from a related VCU faculty team indicated that roughly ⅓ of all VCU students experience some level of food insecurity. Inventions to remedy this dire situation will require a more complete picture of the campus food environment. This project documented aspects of that environment. Our research team surveyed vending machines within Monroe Park buildings and facilities, along with nearby corner stores that were easily accessible to the university. Our team employed two instruments from the nationally recognized Nutritional Environment Measure Survey (NEMS), a toolkit created by Penn State University, to determine the nutritional quality of the campus food environment through direct observation. In addition to the NEMS data collection, our research team administered virtual student questionnaires to gauge general usage and attitudes towards food options on campus. VCU students were surveyed between Fall 2020 and Spring 2021 during the COVID-19 pandemic; and our data collection pivoted to incorporate the effects of the pandemic on campus. Findings are compiled in a geospatial map of the Monroe Park campus and surrounding areas. Within the interactive map, vending and corner store options were identified by the NEMS award systems along with their observation notes. Our findings concluded all snack and some beverage machines on campus received no NEMS award due to the lack of healthy options. Our hope in representing the data in a visually informed layout will incite action by the university administration to implement new opportunities to ensure a healthy and balanced food environment for the VCU community.
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Activity of Saccharomyces cerevisiae by Single Entity Electrochemistry
John Lutkenhaus
According to the Centers of Disease Control and Prevention, antibiotics decrease in effectiveness as bacteria gain resistance for previously treatable illnesses. Currently, antibiotic susceptibility is typically carried out via the Kirby-Bauer method. Even with automation, this process requires two incubation periods so a less time-consuming technique is desirable. Single entity electrochemistry (SEE) detects changes in current when collisions of individual particles at an ultramicroelectrode (UME) are linked with an electrochemical event. Our group has obtained step-like and spike-like responses of Saccharomyces cerevisiae at the UME surface as a result of adsorption and desorption, respectively. This response is due to the blocking of redox molecules from reaching UME surface and therefore related to several factors including particle geometry. We have used COMSOL software to model blocking events of a stationary particle on the UME. The cell was considered as a sphere to block diffusive flux of redox molecules with magnitude dependent upon location on the XY plane. Future work includes investigating conditions to select for adsorption so that electrochemical communication of cells may be observed using a two-mediator system for probing redox sites extra- and intracellularly. Upon completion of these studies, insights may be gained into collisional dynamics of cells at UMEs as well as real-time monitoring of cell metabolism using SEE.
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Influence of Telephone Preoperative Evaluations on Patient Medication Compliance on Day of Surgery
Emmanuel Magsino, Michael Jung, and Olga Suarez MD
Patient compliance with medication instructions on day of surgery (DOS) is an important part of the preoperative assessment, as failure to comply with these may lead to serious perioperative consequences. Prior studies have shown that compliance increases with multimodal interventions. However due to the recent COVID-19 pandemic, many in-person visits transitioned to telephone visits and providers had to rely on patients to follow solely verbal instructions.
To determine medication compliance, this study compared the medication instructions provided by the VCU Preoperative Assessment Communication and Education Clinic, per chart review, with each patient’s own report of which medications they took on the morning of surgery. Secondary outcomes included demographics potentially associated with patients’ compliance such as age, education level and ASA physical status class, which were obtained from the patient's EMR.
Out of a total of 80 (100%) surveyed patients, fifty six patients (70%) understood and were compliant with medication instructions. Among this group of participants, thirty two (57%) patients had completed some college education or higher level. Our results suggest that telephone assessments seem to be an effective means of achieving patient medication compliance on the day of surgery and that education level seems to influence likelihood of compliance. These preliminary results will help us further refine our survey questions and identify other areas to further improve DOS medication compliance.
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Vasculogenic Mimicry: Role of melanoma differentiation associated gene-9/syntenin
Jinkal Modi, Anjan Pradhan, Luni Emdad, Swadesh Das, and Paul Fisher
Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify a new non-angiogenesis-dependent pathway vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like network, such as plasma and red blood cells. The co-generation of endothelial cells, channels, laminar structures, and heparin sulfate proteoglycans are the main pathophysiological characteristics of VM in human melanoma patients. In highly aggressive melanoma cells downregulation of vascular endothelial cadherin and upregulation of ECM components promote the perfusion of the VM pathway. We investigated whether mda-9/syntenin, a pro-metastatic gene, affects VM in MM. The expression of mda-9/syntenin was modulated using gain-of-function and loss-of-function strategies to determine its potential role in VM. Downregulation of mda-9/syntenin in aggressive melanoma cells decreases VM, while over expressing mda-9/syntenin in immortalized melanoma cells increases VM. These findings shed light on a novel role and molecular mechanism of action of mda-9/syntenin in VM, which may contribute significantly to the metastatic phenotype of these aggressive cancers.
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Victimization and Psychological Wellbeing among Sexual and Gender Minority Emerging Adults: Testing the Moderating Role of Emotional Comfort from Companion Animals
Jennifer L. Murphy, Camie A. Tomlinson, Angela Matijczak, Kelly O'Connor, and Shelby McDonald
Introduction: Human-animal interaction science is a growing field, largely due to the potential psychosocial benefits companion animals provide to humans. One way companion animals may influence psychosocial outcomes is through their ability to provide emotional comfort, though few studies have examined relationships between sexual and gender minority stressors (i.e. discrimination, victimization, rejection), human-animal interaction, and psychological wellbeing. To address this gap in the literature, the current study evaluates whether, and to what extent, the association between gender-based victimization and psychological wellbeing (i.e., anxiety, depression, self-esteem) varies as a function of emotional comfort from companion animals among emerging adults.
Methods: Data were collected from young people between the ages of 18 and 21 years who self-identified as a sexual and/or gender minority (N = 134; 37.3% ethnic/racial minority; 49.2% gender minority; 98.5% sexual minority). We conducted three simple moderation analyses that examined whether, and to what extent, gender-based victimization was associated with mental health (i.e., anxiety, depression, self-esteem) as a function of comfort from companion animals. Additive multiple moderation models were also conducted to examine comfort from companion animals and social support as moderators between victimization and each psychological wellbeing indicator.
Results: Results of the simple moderation models suggest that the effect of gender-based victimization on self-esteem was moderated by comfort from companion animals (ΔR2 = .03, F(1, 125) = 4.66, β = .22, t(125) = 2.16, p = .03) and that the relationship is statistically significant only at low levels of comfort from companion animals (β = -0.38, t = -2.41, p = .02). Further, our additive multiple moderation model with both comfort from companion animals and social support as moderators of the relation between victimization and self-esteem found that victimization was significantly moderated by comfort from animals (ΔR2 = .03, F(1, 123) = 5.38, β = .24, t(123) = 2.32, p = .02), but not social support. The relation between victimization and self-esteem was significant and negative at low levels of comfort from companion animals, but only for those with high levels of social support (β = -0.43, t = -2.65, p < .01). In contrast, when high levels of comfort from companion animals were reported, the effect of victimization on self-esteem was no longer statistically significant, regardless of whether social support was low or high. We did not find evidence of moderation in models with either anxiety or depression as the dependent variable.
Conclusion: These results suggest that high levels of comfort from companion animals may be a protective factor against the harmful effects of victimization on self-esteem. However, our results suggest that comfort from companion animals may not provide the same benefits for anxiety and depression. Further research is needed to replicate our results and to elucidate whether other aspects of HAI, such as attachment to pets or caretaking for pets, may play a role in associations between victimization and anxiety and depression. Given the harmful effects of gender-based victimization and other stressful circumstances that LGBTQ+ youth are disproportionately at risk of experiencing (i.e., employment issues, housing insecurity), this study highlights the importance of exploring how, and for whom, comfort from companion animals and other aspects of HAI may provide protective benefits.
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Pharmacogenomics and SSRIs Appropriateness in Older Community Dwelling African Americans
Wint War Phyo, Lana Sargent, and Elvin T. Price
Background: Depressive and anxiety disorders are among the most common illnesses experienced by older adults (age > 60). The selective serotonin reuptake inhibitors (SSRIs) are preferred class of antidepressants for these disorders due to their high efficacy and safety profiles among older adults. However, SSRIs are metabolized by highly polymorphic cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19. This can lead to variable dose-response outcomes, especially among older African American population.
Objective: Analyze the frequency of CYP2D6 and CYP2C19 polymorphisms in African American older adults who are taking SSRIs and identify potential inappropriate use of SSRIs in these older adults using the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines.
Methods: Participants (age > 60) were enrolled into Translational Approaches to Personalized Health (TAPH) study. DNA samples were collected via Ora-gene saliva kits and the DNA was analyzed using the PGx Express Chip on the QuantStudio 12K Flex system. After quality control was performed, we focused on the genotypes of 12 participants who were prescribed SSRIs.
Results: Only 2 participants had normal activity levels of both CYP2D6 and CYP2C19, while the rest had at least one variant allele that resulted in decreased or increased enzyme activity level. After matching the participants’ enzyme activity levels with the major metabolic pathway of their agent of SSRIs, 8 out of 12 participants are at risk of experiencing sub- or supra-therapeutic effects of SSRIs. 2 participants, especially, are at increased risk of serious adverse effect of citalopram-induced prolonged QT interval, which is more prevalent in older adults.
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Radiation Induces Metabolic Dysregulation in Pulmonary Fibroblasts
Josly Pierre-Louis, Margaret A. T. Freeberg, Jane K. Rebman, Thomas H. Thatcher, and Patricia J. Sime
Rationale: Exposure of the lung to ionizing radiation, such as during radiotherapy, can result in pulmonary fibrosis (PF), which has few treatment options. PF is characterized by an accumulation of extracellular matrix proteins that form scar tissue, resulting in dyspnea, disruption of gas exchange, and even death. We and others have shown that metabolic reprogramming is a hallmark of idiopathic pulmonary fibrosis (IPF). IPF lung tissue, and lung fibroblasts treated with TGF-β, exhibit increased aerobic glycolysis with increased expression of lactate dehydrogenase A (LDHA) and excess production of lactate, leading to reduced extracellular pH that activates latent TGF-β. Here, we hypothesized that ionizing radiation would cause aerobic glycolytic metabolic dysregulation in primary human lung fibroblasts.
Results: Primary non-fibrotic HLFs exposed to irradiation exhibited significant upregulation of Pyruvate Dehydrogenase Kinase (PDK1 (0.5 – 3-fold, p<0.05) and LDHA (1.4-fold, p<0.05). Cell viability was unaffected by increased radiation dose.
Conclusions: Radiation increased fibroblast expression of genes involved in fibrotic phenotypes (αSMA) and aerobic glycolysis (PDK1 and LDHA), in a similar pattern to that seen in IPF fibroblasts. The metabolic changes are closely associated with creating a profibrotic extracellular environment in IPF by promoting an acidic environment. Our evidence suggests this phenomenon can be driven by radiation in lung fibroblasts and affirm that glycolytic reprogramming may also be a hallmark of radiation-induced fibrosis. Further understanding of the common mechanisms that create this metabolic shift could provide novel therapeutics for fibrosis treatment.
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Device-Related Adverse Events From WATCHMAN FLX Implants As Reported By The Food And Drug Administration
Dongjin Suh BS, Paul Eugene Kim BS, Emmanuel Magsino BS, and Tae Shik Park
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Carotid artery dissections from TCAR as reported by the Food and Drug Administration
Dongjin Suh BS, Yuchi Ma BS, Daniel H. Newton MD, Michael F. Amendola MD, and Kedar S. Lavingia MD
BACKGROUND: Transcarotid artery revascularization (TCAR) is hybrid procedure that allows carotid stenting using direct surgical access of the carotid artery to restore blood flow through the carotid artery. It has shown the lowest perioperative stroke rate when compared with any prospective trial of transfemoral carotid artery stenting. However, intraoperative injuries related to the procedure and its management are not well characterized. We anticipate that this analysis will add qualitative insight in further characterizing adverse outcomes of this novel technology.
METHODS: The FDA maintains a database called the MAUDE (Manufacturer and User Facility Device Experience) for surveillance of all medical devices approved for use. This database was queried for all cases associated with Silk Road Medical’s ENROUTE Transcarotid Neuroprotection System from September 2016 to October 2020.. Case narratives related to patient injuries were individually analyzed to determine type (carotid artery dissection) and time of injury (intraoperative, recovery, post-discharge follow- up). Carotid artery dissection (CD) reporting was further analyzed for associated procedural event at the time of injury, number of access attempts to CD repair, and type of CD repair.
RESUTS: Of the 115 unique incidents in the database, there were 58 CDs. Most were identified intraoperatively (n=55), while 3 were incidentally identified postoperatively. Overall, sheath placement was the most common procedural event attributed to CD (n=34). There was adequate narrative information about CD repair in 54 patients where 52 of them were performed intraoperatively. There were total of 28 endovascular repair and 24 open surgical repairs of CDs from TCAR procedure.
There was no significant difference in rate of endovascular and open surgical repair of CDs that did not need additional access attempts. However, rate of open surgical repair was significantly higher in CDs with persistent failure to engage the true lumen in 2 or more additional access attempts.
Total of 4 strokes were associated with CD. Two occurred during recovery from TCAR admission where one was not intervened per physician’s discretion despite evidence of dissection during the procedure. The other was associated with a fall from a hypotensive event 7 hours after an endovascular CD repair. One incident of stroke occurred intraoperatively during a conversion to CEA as a result of CD. One incident of stroke occurred 4 days after TCAR procedure in which a CD was identified during the stroke evaluation
Conclusion: Carotid artery dissection is the most common injury related to TCAR as reported on MAUDE database. Most common procedural event associated CD was sheath placement. Rate of open surgical repair was significantly higher than endovascular repair in dissections with persistent failure to engage true lumen despite additional access attempts. This should add to qualitative insight among vascular surgery community regarding intraoperative management of carotid artery dissections from a TCAR procedure.
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PRINCIPAL COMPONENTS ANALYSIS CORRECTS COLLIDER BIAS IN POLYGENIC RISK SCORE EFFECT SIZE ESTIMATION
Nathaniel S. Thomas, Peter B. Barr, Fazil Aliev, Sally I. Kuo, Danielle M. Dick, and Jessica E. Salvatore
BACKGROUND: Genome-wide polygenic scoring has emerged as a way to predict psychiatric and behavioral outcomes and identify environments that promote the expression of genetic risks. An increasing number of studies demonstrate that the effects of polygenic risk scores (PRS) may be biased by the inclusion of heritable environments as covariates when the environment is influenced by unmeasured confounding variables, an example of collider bias. Inclusion of the principal components of observed confounders as covariates may correct for the effect of unmeasured confounders.
METHODS: A simulation study was conducted to test principal components analysis (PCA) as a correction for collider bias. Data were sampled from a model which tested different values for the effect of the polygenic risk score on the heritable environment, the correlation structure of the unmeasured confounding data, and the proportion of the confounding data that is used to construct the principal components. Other model parameters were fixed across all simulation iterations.
RESULTS: Modeling the first PC of observed confounders as a covariate recovers the PRS effect size estimate under reasonable assumptions about the proportion of the confounding data that is measured or the correlation structure of the confounding data. Required assumptions become stricter as the effect of PRS on environment (and the magnitude of bias) increases.
CONCLUSION: Inclusion of the first PC of observed confounders as a covariate may improve the accuracy of PRS effect size estimation when heritable environments are included in the model as covariates. Future directions include application of this method in observed data.
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She’s Not Forgotten: School Counselors in the pursuit of ending the school push out of Black Girls
Christina Tillery
Professional school counselors play a critical role in ensuring that ALL students have access to quality education free from discrimination. Inequitable discipline practices and systemic racism have hindered the academic and social/emotional development of Black girls. This workshop will help school counselors learn how to identify discriminatory practices, analyze current national data, and provide resources to implement supports and interventions in their schools. The last decade has seen major court cases reflecting social changes affecting school counselors' legal and ethical obligations. Learn about principles of practice emerging from recent court rulings involving sexually active students, educational records, transgender youth, child abuse, social media, suicide, and academic advising.
Participant learning outcomes:
After attending this session you should be able to:
1. Identify discriminatory practices common in public schools
2. Analyze current national data on Black girls’ experiences in public schools
3. Implement evidence-based interventions to support Black girls
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Relations Between Sexual and Gender Minority Stress, Personal Hardiness, and Psychological Stress in Emerging Adulthood: Examining Indirect Effects via Human-Animal Interaction
Camie A. Tomlinson, Jennifer L. Murphy, Angela Matijczak, and Shelby E. McDonald
Introduction: Although there is emerging evidence that companion animals are important sources of comfort and support for many LGBTQ+ (lesbian, gay, bisexual, transgender and other sexual and gender minority identities) individuals, little is known about the interplay between sexual and gender minority (SGM) stress, human-animal interaction (HAI), and psychological adjustment in this population. To address this gap in the literature, the current study examined the role of HAI in relations between SGM stress (i.e., microaggressions, victimization) and psychological adjustment (i.e., self-efficacy, psychological stress) during emerging adulthood.
Methods: Our sample included LGBTQ+ young adults between the ages of 18 and 21 years (N = 136; 37.5% racial/ethnic minority; 49.2% transgender or gender-expansive; 98.5% sexual minority). Participants were recruited via convenience sampling methods in partnership with community agencies. We tested a mediation model using structural equation modeling with a bootstrapping approach to examine direct and indirect associations between SGM stress, HAI, and psychological adjustment, controlling for the effects of demographic factors.
Results: The hypothesized mediation model fit the data well (Χ2/df = 1.71, CFI = 0.96, TLI = 0.93, RMSEA = 0.07, SRMR = 0.04). Results indicated that SGM microaggressions were significantly associated with HAI (β = 0.45, p < .001, 95% CI [0.24, 0.62]) and psychological stress (β = 0.36, p < .001, 95% CI [0.19, 0.54]), but not self-efficacy. Victimization was not significantly associated with HAI, self-efficacy, or psychological stress. HAI was significantly and positively associated with self-efficacy (β = 0.31, p < .001, 95% CI [0.13, 0.47]), but was not significantly related to psychological stress. Finally, we found evidence of only one indirect-only effect of SGM microaggressions on self-efficacy via HAI (β = 0.14, p = .001, 95% CI [0.07, 0.24]).
Conclusion: This is the first study, to our knowledge, that explored the potential mediating role of HAI in the relations between SGM microaggressions, victimization, self-efficacy, and psychological stress. Results of this study suggest that exposure to SGM stress may lead LGBTQ+ young adults to seek out relationships with pets, which in turn, may promote self-efficacy, a factor associated with resilience. However, due to the cross-sectional nature of our data, we cannot infer causation. Further research is needed to explore the longitudinal reciprocal associations between SGM stress, HAI, and psychological adjustment over time, and mechanisms through which HAI may promote resilience in this population.
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Extending Single Entity Electrochemistry Towards the Detection of Single Bacteria in Micro Volumes
Ashley Tubbs, Junaid Ahmed, and Julio C. Alvarez
Single entity electrochemistry (SEE) is an emerging electroanalytical technique with the ability to push the limit of detection of electrochemical sensors to the single particle level. It measures the change in current over time, making SEE rapid, simple, and cost-effective. The type of current response observed in the scan can provide information about the physiochemical processes underlying the signal. While SEE was originally developed to detect single molecules and nanoparticles, it has been widely applied to micron-sized particles, including emulsion droplets, bacteria, viruses, and mammalian cells. Some recent advances in this technique have focused on the detection of microscopic quantities of cells, with the goal of detecting bacteria in agricultural samples. Picomolar levels of detection were recently achieved for single bacterial cells in bulk solution (Anal. Chem. 2018, 90, 20, 12123-12130). To further lower the level of detection, we have demonstrated that SEE can successfully detect Escherichia coli bacterial cells trapped in a micron-sized droplet at the surface of the electrode. The micro-sized droplet shows a lower level of detection similar to that of the bulk solution: at the femtomolar level. Interestingly, we have observed a two- to four-fold decrease in the current response time in the microenvironment vs the bulk.
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Family Learning Culture Assessment: Development of metrics of the collective epistemic orientations and achievement motivations in diverse families
Catina Venning
The family, in educational psychology research, is unidimensional. It is either a covariate, a tool for school agenda or narrowly defined by a single person, usually the mother and her college educational attainment. These diminutions of family hamper efforts to fully understand critical contextual factors that impact student learning, like family. Inspired by Cultural Historical Activity Theory (CHAT) and Family Communication Practices (FCP), Family Learning Culture Theory (FLCT) emerged as the conceptual framework for a exploratory research project, which interviewed three middle-class family representatives, of high school students in two school districts in a Southeastern city in the United States. Aggregate findings, from that preliminary study reveal that family expectations towards learning, school and knowledge, is shaped academic success is a multi-membered, cultural dynamic which extends beyond households and bloodlines. This study also found that over time, family is less directive and more consultative in its support for children’s personal fulfillment and goal attainment, which may not include college. The results of this study informed the development of the Family Learning Culture Assessment, which combines interdisciplinary, reliability-tested, metrics along with new dimensions unearthed during the qualitative study, to understand emergent family typologies in school-based settings. This research and the resulting assessment have implications for removing deficit-based binaries, like engaged or disengaged, and replacing them with more nuanced descriptive typologies, reflective of families as complete cultural entities. The possibilities for targeted support or intervention are as varied as the typologies themselves.
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Colobinae evolution: Using GIS to map the distribution of leaf monkeys across Southeast Asia over time
Marie Vergamini, Christina McGrath, and Lisa M. Day
The Colobinae, or leaf monkeys, are distributed geographically across Africa and Asia. Colobinae are specialized arborealists and leaf eaters with sacculated stomachs, sheering teeth, reduced thumbs, and very mobile shoulders. Colobinae diverged ~10.9 million year ago (Ma) from the Cercopithecidae in Africa, and Asian colobines appear in the fossil record in the late Miocene ~8.5 Ma. However, an incomplete fossil record means little is known about the evolutionary pressures that led to Asian colobine migration and diversification. Here, we use recent fossil discoveries and geospatial information to develop hypotheses about how geographic barriers played direct roles in Asian colobine evolution.
Using ArcGIS, we plotted Miocene-epoch to Pleistocene-epoch fossil Colobinae collection sites with overlapping geospatial information including geographic barriers that may have influenced species distribution like the Himalayas and the Hengduan Mountains. We also included extant species’ presence, distributions, and species diversity to assess patterns of distribution over time. Data from each epoch were compared to track species distribution over time.
Results suggest that combining fossil data, extant species’ distributions, and biogeographically relevant geospatial elements provides some parameters for where and when Colobine adaptions were selected for. For example, cold climate adaptions in certain Asian Colobines, especially Rhinopithecus, are not recent and have shaped how that genus is distributed today. These parameters can support powerful hypothesis building about the evolutionary histories of extant species adapting behaviorally and anatomically to densely forested South East Asia.
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Modeling Longitudinal Change in Cervical Length Across Pregnancy
Hope M. Wolf, Shawn J. Latendresse, Jerome F. Strauss III, and Timothy P. York
Introduction: A short cervix (cervical length < 25 mm) in the mid-trimester (18 to 24 weeks) of pregnancy is a powerful predictor of spontaneous preterm delivery (gestational age at delivery < 37 weeks). Although the biological mechanisms of cervical remodeling have been the subject of extensive investigation, very little is known about the rate of change in cervical length over the course of a pregnancy, or the extent to which rapid cervical shortening increases maternal risk for spontaneous preterm delivery.
Methods: A cohort of 5,160 unique women carrying 5,971 singleton pregnancies provided two or more measurements of cervical length during pregnancy. Cervical length was measured in millimeters using a transvaginal 12-3 MHz ultrasound endocavity probe (SuperSonic Imagine). Maternal characteristics, including relevant medical history and birth outcome data, were collected for each participant. Gestational age at delivery was measured from the first day of each woman’s last menstrual period and confirmed by ultrasound. Repeated measurements of cervical length during pregnancy were modeled as a longitudinal, multilevel growth curve in MPlus. A three-level variance structure was used to account for non-independence of repeated measurements clustered within pregnancies, which are clustered within participants.
Results: The average number of cervical length measurements per pregnancy is 6. Shorter mid-trimester cervical lengths and accelerated rates of cervical shortening are associated with shorter gestational duration. A smaller initial cervical length (p < 1*10-4) and a faster rate of change in cervical change length during pregnancy (p < 1*10-4) are significantly associated with an earlier gestational age at delivery. A higher pre-pregnancy body mass index (BMI) is associated with shorter initial cervical length in early pregnancy (p < 1*10-4), while maternal age is associated with a more rapid rate of change in cervical length (p < 1*10-4). Parameters describing cervical length and its rate change during pregnancy (i.e., intercept, linear slope, and quadratic slope parameters) explained 59% more variance in gestational age at delivery than a single mid-rimester cervical length measurement, which is the current gold standard in clinical practice. However, a significant amount of residual variance in individual estimates of cervical length growth parameters remains (p < 1*10-4), which could be accounted for, in part, by common variation in the population.
Conclusion: We have developed longitudinal models of cervical length that describe individual and group level trajectories of cervical change across pregnancy. Extensions of this model incorporating genomic data, can be used to estimate the heritability of cervical length and its role in mediating the timing of birth.
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The Effect of Self-Rated Health and Race/Ethnicity on the Relationship Between Feelings of Content and Frequency of Seeing their Primary Care Provider
Alexandra Wynn and Kristina Beatrice Hood
Racial and ethnic minorities face significant health disparities as they are less likely to receive preventive health services, receive lower-quality care and have worse health outcomes for many chronic conditions than White people (Hostetter, Klein, 2018). Thus, it is important to analyze what psychological and social factors affect these populations and how they contribute to healthcare engagement. One psychological correlate that has not been focused on is self-rated health. Self-rated health has mainly been analyzed for its relationship with personality and physiological factors but little research has focused on how it influences seeking medical care. Fair/poor self-rated health was found to be associated with greater distrust in the health care system in a primarily White sample (Armstrong et al., 2006). In this way, self-rated health impedes health as it is associated with failing to follow physician’s advice, failure to seek medical care when they needed it and delays in seeking care (LaVeist, Isaac, & Williams, 2009). In a majority Hispanic/Latinx and White sample, self-rated health was significantly correlated with better patient provider relationships and there was no significant difference in self-rated health among races (Kamimura et al., 2020).
The aim of this study was to investigate how an individual’s self-rated health and race/ethnicity influences the relationship between feelings of content and the frequency at which one sees their primary care provider (PCP) for a checkup. We hypothesized that racial/ethnic minorities who rate their health higher, would see their PCP for a health visit less often when they are more content. Using Amazon’s Mechanical Turk, the researchers administered a questionnaire to 1210 participants measuring demographic information, self-rated health, number of visits to their PCP per year and the World Health Organization Quality of Life- Feeling or Experiences Subscale. Our study used one item from the Feeling or Experiences Subscale referring to how often the participant felt content over the past two weeks. A moderated moderation using Hayes’(2020) PROCESS macro was conducted. There was a significant main effect of self-rated health on frequency of seeing their PCP, b = 0.12, p < .001. Additionally, there was a significant main effect on the difference between how many Black participants compared to White participants went to see their PCP, b = -0.21, p =.0265. There was a significant three way interaction between feelings of content, self-rated health and being Black on seeing their PCP for a checkup (Figure 1). When a Black individual’s self-rated health is low, they are less likely to visit their PCP for a checkup when they are more content, b = -0.07, p =.0421.
These results significantly add to the literature as it provides more clarity on how individuals perceive their health affects the rate in which they see their PCP. Our hypothesis was supported for White participants as feelings of content and self-rated health did not affect the rate in which they sought medical attention. However, our hypothesis did not support all racial/ethnic minorities outside of Black participants as feelings of content and self-rated health did not moderate the relationship between feeling content and seeing their PCP. These results are similar to prior research as African Americans have been studied to delay or avoid seeking care due to discriminatory and biased past health care experiences. If a Black individual rates their health as high, they are less likely to go to the doctor due to lack of trust in health professionals and the health care system. More research needs to be conducted in other racial/ethnic minorities to identify what factors influence seeking medical care. Identifying these experiences and perceptions of health in marginalized populations can help advance the patient-provider relationship and improve the importance of maintenance of good health.
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Dose Deposition and Electrostatic Charging of Kapton Films Irradiated with Electrons
Youssef Abouhussien and Gennady Miloshevsky
Kapton films are widely utilized in harsh radiation environments where radiation resistant insulating materials are required. For space applications, Kapton polymers are used on satellites as substrates for solar arrays and outer layers of thermal systems. Kapton is also used in nuclear power plants as wire insulation. Kapton materials can be exposed in nuclear reactors to a reactive chemical environment in addition to severe radiation. It is of utmost important to understand how Kapton materials behave under high irradiation conditions and mitigate radiation damage effects. High-energy electrons can deposit ionizing dose and electric charge deeply inside Kapton materials. The charge accumulation grows over time and may exceed the dielectric strength of Kapton resulting in the electrostatic discharge that may cause extensive material damage. The dose deposition and electrostatic charging of Kapton irradiated with electrons has been studied using the Monte Carlo stepping model implemented in the Geant4 software toolkit. The secondary radiation emission (photo-, Auger-, Compton-electrons, and fluorescence photons) generated by primary electrons is taken into account in the redistribution of dose and charge deposition within a Kapton film. The results of this study are the profiles of dose and charge deposited by primary and generated secondary electrons and photons within a thin film of Kapton as a function of its depth. The results also provide insights into distributions of dose and charge in Kapton films under various incidence angles and energies of electrons.
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Temporal Behavior of the Individual Soft Microparticles: Understanding the Detection by Particle Impact Electrochemistry
Junaid Ahmed and Julio C. Alvarez
Emerging progress of the Particle Impact Electrochemistry (PIE) technique has opened a novel field of detection and characterization of many analyte particles. 1 PIE comprises detection of changes in current when collisions of individual micro or nanoparticles are linked with an electrochemical event at the surface of an ultramicroelectrode (UME). 2 Being a rapid, low cost, and analyzing of one analyte at a time, PIE is widely used to characterize the shape, size distribution, and catalytic activity of nanoparticles. 2-5 To explore the scope of PIE for the detection of soft microparticles (absence of crystalline structure), ferrocene (Fc) trapped toluene-in-water emulsion droplets was used as a model with ultramicroelectrode. Droplets were analyzed by tracking the oxidation of Fc inside the droplet in the presence of an ionic liquid acting as emulsifier and conductivity enhancer. The droplet diameter was determined electrochemically using Faraday’s law. PIE was able to characterize the polydisperse size distribution of the droplets successfully. A 3D lattice random walk simulation indicated the stochastic nature of the droplet motion. Unlike nanoparticles, the droplets have slow kinetics and the collision dynamics associated with adsorption on the electrode surface. The adsorbing droplet generated similar spike-like electrical signals in real-time experiments that follow the bulk electrolysis model. These findings will facilitate the characterization of polydisperse microparticles including bacteria, which also adsorb and have similar size and density as the droplets in this work. Finally, because electrolysis time spans from hundreds of milliseconds to a second, single events of such duration are detectable with present-day instrumentation in contrast to non-adsorbing nanoparticles that have nanosecond collisions.
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Local Lung Targeting of Tumor Associated Macrophages Combined with Cytoreductive Therapy Decrease Tumor Burden in a Secondary Lung Cancer Model
Sulaiman Alhudaithi, Hanming Zhang, Rashed Almuqbil, Wei Du, Fatemah Sunbul, Paula Bos, and Sandro da Rocha
Backgrounds. The efficacy of a locally administered small molecule colony stimulating factor 1 receptor inhibitor (CSF-1Ri), PLX3397, alone or in combination with cytoreductive therapy (paclitaxel) in reducing the tumor burden of an in vivo model of secondary lung cancer was investigated in this work. Local administration of immunotherapy to the lungs may enhance lung biodistribution of such therapies and reduce potential unwanted off-target toxicity. In addition, combination of such therapy with low dose standard of care chemotherapy may offer improved anti-tumor effects.
Methods. Murine breast cancer cells (4T1, known to be highly metastasized to the lungs) were transduced to express the genes luciferase and tdTomato, and cells were injected to female Balb/c mice before being treated with PLX (intratracheally administered), paclitaxel (intravenously given), or the combination therapy. Both ex vivo bioluminescent imaging and lung weights were used to evaluate tumor burden. Western blot was performed using lung tumors to assess the effect of PLX3397 on its molecular target (phosphorylated CSF-1R). Immunofluorescence and Flowcytometry were utilized to examine the impact of treatment on tumorigenic tumor associated macrophages (M2 TAM).
Results. Single-agent treatment partially decreased tumor burden, while combination therapy led to a significant reduction in tumor burden. PLX3397 significantly inhibited the expression of phosphorylated CSF-1R and reduced the number of M2 TAM without affecting the total macrophage population, thereby increasing the anti-tumorigenic (M1)/M2 ratio.
Conclusion. Tumor burden reduction upon local administration of PLX3397 to the lungs correlates with the marked inhibition of the molecular target and the decrease in M2 TAM.
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Dendrimer Conjugation Enhances Tumor Penetration and Cell Kill of Doxorubicin in 3D Coculture Lung Cancer Models
Rashed Almuqbil, Rodrigo S. Heyder, Elizabeth R. Bielski, Mikhail Durymanov, Joshua J. Reineke, and Sandro R. P. da Rocha
Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX.
Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of (A549) lung adenocarcinoma cells and (3T3) fibroblasts. Spheroids were characterized for ECM components with immunohistochemistry. Confocal microscopy was used to evaluate the penetration, internalization, and colocalization of DOX and G4SA-GFLG-DOX. MTT assay and Caspase 3/7 to assess 2D and 3D cytotoxicity. Flow cytometry to determine cells uptake.
Results: DOX conjugation to dendrimer resulted in G4SA-GFLG-DOX with ~5.5 DOX, 10±1 nm hydrodynamic diameter, and a -17±3 mV zeta-potential. Spheroids of (A549:3T3) were ECM- rich, developed ECM containing collagen-I, hyaluronan, laminin, and fibronectin. While DOX and G4SA-GFLG-DOX had similar toxicities in 2D model, G4SA-GFLG-DOX demonstrated a 3.1-fold greater penetration into spheroids compared to DOX and correlated to a greater efficacy as measured by caspase 3/7 activity. Also, flow cytometry showed higher uptake of G4SA- GFLG-DOX in cancer cells compared to fibroblasts.
Conclusion: The work demonstrates enhanced penetration of DOX, via dendrimer conjugation, into an ECM- rich 3D lung cancer model. The enhanced penetration of G4SA-GFLG-DOX correlated with greater antitumor efficacy.
Acknowledgements: We acknowledge partial financial support from the Center for Pharmaceutical Engineering and Sciences - School of Pharmacy at VCU. This study was supported by VCU Quest for Distinction and NSF (DRM #1508363). Microscopy was performed at the VCU Microscopy Facility, supported, in part, by funding from NIH-NCI Cancer Center Support Grant P30 CA016059. RA would like to acknowledge King Faisal University (KFU) and Saudi Arabian Cultural Mission (SACM) for a scholarship.
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Development of an R script for simple lipidomic and metabolomic data analysis
Suad Alshammari, Joshua M. Morriss, Daniel Contaifer, Dayanjan S. Wijesinghe, and Monther Alsultan
Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures.
Methods: R scripts were developed under version 3.5.3 with the capability to undertake statistical analyses (e.g. ANOVA) and post-hoc tests (e.g. Tukey). Additional code plotted resultant information as high resolution violin and box plots that depicted statistical significance. Thereafter, lipidomic and metabolomic data were analysed by this code and compared against commercial software and Metaboanalyst, a primary software used in metabolomic and lipidomic research.
Results: Code generated in house demonstrated the same results as those generated using commercial software (e.g. JMP 14.0 Pro) but were different from results obtained by using the MetaboAnalyst pipeline.
Conclusions: This study demonstrated the prevalent danger of using closed-source software pipelines for the analysis of lipidomic and metabolomic data without validating the analysis outcomes via open-source software. Open source software such as LipidAnalyst, that has also been independently validated using multiple data sets, can then be published with the results to enable transparency of data analysis and improve the replicability of results across different labs.
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A Pre-transplant Blood-based Lipid Signature for Prediction of Antibody-mediated Rejection in Kidney Transplant Patients
Monther Al sultan, Daniel Contaifer Jr., Joshua Morriss, Suad Alshammari, Jeffrey Stern, Sindhura Bobba, Pamela Kimball, Anne King, Dhiren Kumar, Marlon Levy, Gaurav Gupta, and Dayanjan Wijesinghe
Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients.
Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to create Linear Discrimination Analysis with regularized correction (RLDA). Changes over time were estimated using sparse partial least square method which is validated by permutation testing. T-test was performed to compare two time points for the same group and groups at matched time points. JMP Pro 13 and MetaboAnalyst were used in the analysis of the Data.
Results. A comparison of lipids classes on the day of transplant revealed PLs relative concentration differences between SC and AMR. Concentration of phosphatidylcholine (PC) was significantly diminished in AMR, while there was a trend for increased concentration of lysophosphatidylcholine (LPC). AMR group also showed significantly lower concentration of phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), plasmanylethanolamine (PE-O), and plasmenylethanolamine (PE-P). Our data demonstrated that there are significant differences in the lipidome between SC and AMR on the day of transplant. The analysis identified 7 distinct lipids that discriminated between AMR and SC (AUC) =0.95 (95%CI=0.84- 0.98), R2=0.63 (95%CI=0.4-0.8). A sPLSDA analysis of the data revealed a statistically significant alteration in the lipid profile at 6 months post-transplant compared to the day of transplant. The analysis revealed a panel of 13 lipids that were found to differentiate the two groups at 6 month post-transplant . Further data analysis confirms the presence of a sustained lipid metabolic difference between SC and AMR over time that distinguish between the patients with favorable and non-favorable transplant outcomes.
Conclusion. This study demonstrates the potential of the pre-transplant lipidome towards determining AMR in kidney transplant patients, raising the possibility of using this information in risk stratification of patients about to undergo transplant.
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Addressing Minority Health Disparities in Richmond: Results from a Health Needs Assessment of a Southside Community
Nixon Arauz, MA; Shanteney Jackson, MA; and Robert A. Blanco, MPH
Background:
Evidence shows the effectiveness of integrating community health workers (CHWs) into care models serving high-risk patients to reduce emergency department (ED) use, increase primary care use, and address adverse social determinants of health (SDH). The Southwood Resource Center, part of a network of clinics established by Richmond City Health Department, utilizes CHWs to address disparities affecting underserved populations through primary care referrals and additional resource linkages. Local student-volunteers in partnership with CHWs conducted a community needs assessment to identify patient resource gaps, aid in design and implementation of SDH interventions, and examine the relationship between chronic disease management and ED use reductions.
Methods:
English and Spanish-language surveys were conducted during patient visits to the SRC, in addition to other settings to facilitate representative sampling. A total of 134 responses were received, with Blacks (34%) and Hispanic/Latinos (65%) well represented.
Results:
Significant social determinants identified by the needs assessment included housing stability, and transportation and food access. Respondents indicated need for support managing chronic conditions including heart disease, diabetes, mental health and asthma. 1 in 3 respondents (31%) reported using the ED for primary care, and nearly 2 in 3 (66%) reported not having a family doctor. Barriers to health care included cost (35.6%), insurance status (50.4%) and transportation access (29.6%).
Conclusions:
CHWs play an important role in identifying community strengths and resource gaps and linking patients to additional resources. Opportunities for service improvements include bilingual care coordination, chronic care management, health insurance navigation, food subsistence resources, and transportation support.
