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.
- Collisions or Adsorption: An Electrochemical Random Walk Decides by Junaid U. Ahmed and Julio C. Alvarez [View Image]
Junaid U. Ahmed and Julio C. Alvarez
Current-time recordings of toluene microdroplets emulsified in water and containing 20 mM Ferrocene (Fc), show multiple electrochemical peaks from oxidation of Fc on disk microelectrodes (5μm-diameter). The average droplet diameter (~0.7 μm) determined from area integration of the peaks was close to Dynamic Light Scattering measurements (~1 μm). Random walk simulations were performed deriving equations to simulate droplet electrolysis using the diffusion and thermal velocity expressions established by Einstein. The simulations show that multiple droplet-electrode collisions, lasting ~0.11 μs each, occur before a droplet wanders away. Updating the Fc-concentration at every collision shows that a droplet only oxidizes ~0.58 % of its content in one collisional journey. In fact, it would take ~5.45 x 106 collisions and ~1.26 h to electrolyze the Fc in one droplet with the collision frequency derived from the thermal velocity (~0.52 cm/s) of a 1μm-droplet. To simulate adsorption, the droplet was immobilized at first contact with the electrode while the electrolysis current continued to be iteratively computed until the end of the simulation. This approach along with modeling of instrumental filtering produced the best match of experimental peaks, which were attributed to electrolysis from single adsorption events instead of elastic collisions. These results point to a heightened sensitivity and speed when relying on adsorption instead of elastic collisions. The electrochemical current for the former is limited by the probability of adsorption per collision, whereas for the latter, the current depends on the collision frequency and the probability of electron transfer per collision.
- Peptidomimetic and Non- Peptidomimetic Derivatives as Possible SARS-CoV-2 Main Protease (Mpro) Inhibitors by Mohammed A. Al Awadh, Mohini S. Ghatge Ph.D, Mona A. Al Khairi, Faik N. Musayev, Akua K. Donkor, Mohammed H. AL Mughram, Abdelsattar M. Omar Ph.D, Moustafa M. El-Araby Ph.D, and Martin K. Safo Ph.D [View Image]
Peptidomimetic and Non- Peptidomimetic Derivatives as Possible SARS-CoV-2 Main Protease (Mpro) Inhibitors
Mohammed A. Al Awadh, Mohini S. Ghatge Ph.D, Mona A. Al Khairi, Faik N. Musayev, Akua K. Donkor, Mohammed H. AL Mughram, Abdelsattar M. Omar Ph.D, Moustafa M. El-Araby Ph.D, and Martin K. Safo Ph.D
To design novel inhibitors of the SARS-CoV-2 main protease (Mpro), we investigated the binding mode of the recently reported α-ketoamide inhibitors of this enzyme. Following, we utilized in-silico screening to identify 168 peptidomimetic and non-peptidomimetic compounds that are high probability Mpro binding candidates. The compounds were synthesized in 5 to 10 mg for initial screening for their potential inhibition of Mpro using Fluorescence Resonance Energy Transfer (FRET) assay. The study was conducted using the main protease, MBP-tagged (SARS-CoV-2) Assay Kit (BPS Bioscience, #79955-2), and the fluorescence due to enzymatic cleavage of substrate measured using BMG LABTECH CLARIOstar™, a fluorescent microplate reader, with an excited/emission wavelength of 360 nm/460 nm, respectively. The FRET assay showed 29 compounds to exhibit lower fluorescence compared to the positive control, indicating inhibitory activity, with three of the compounds exhibiting over 50% enzymatic inhibition. The assay average scores were plotted as dose inhibition curves using variable parameter nonlinear regression to calculate the IC50 values. To design more potent inhibitors, an in-silico molecular docking simulation using the SARS-CoV-2 Mpro crystal structure was conducted to investigate on a molecular level the key binding residues at the active site, as well as the possible binding modes and affinity of the lead inhibitors. Additionally, an in-silico study of the compounds' molecular properties and physicochemical profiles was performed to predict their pharmacokinetic properties and assess their suitability as potential orally active drug candidates.
- Frequency of Genetic Polymorphisms of CYP2C19 in Native Hawaiian, and Asian and Pacific Islander Subgroups: Implications for Personalized Medicine by Khalifa Y. Alrajeh and Youssef Roman Dr [View Image]
Frequency of Genetic Polymorphisms of CYP2C19 in Native Hawaiian, and Asian and Pacific Islander Subgroups: Implications for Personalized Medicine
Khalifa Y. Alrajeh and Youssef Roman Dr
Pharmacogenetic testing, where prescriptions are tailored to the individual patient based on his/her genetic makeup, increases the ability to predict individual drug response. However, little is known about the prevalence of clinically actionable pharmacogenes in diverse populations. This study seeks to assess the prevalence of select drug-gene alleles that are implicated in the metabolism of commonly prescribed drugs, so-called Very Important Pharmacogenes (VIPs). The results of this study will fill in the gaps of knowledge of VIPs in underrepresented populations and characterize their potential risk for drug adverse events or due to their underlying genetic polymorphisms, especially in patients of Asian, Hawaiian or Marshallese, or Samoan descent.
The Ensemble genome browser was used to compare the frequencies of three major single nucleotide polymorphisms (SNPs) in the cytochrome P450 subfamily 2 class 19 (CYP2C19) in European (EUR) with our studied populations. Specially, SNPs of interest included rs4244285 G>A, rs4986893 G>A, and rs12248560 C>T, for CYP2C19*2, *3, and *17, respectively. In this cross-sectional study, chi-square or Fisher’s exact test was used, when appropriate, with P < 0.05 for significance.
Biobank DNA samples of 1064 participants were used to calculate genotype and allele frequencies for our population groups. The sample was distributed across six self-reported ethnicities; Filipino (21.61%), Japanese (19.73%), Korean (9.77%), Hawaiian (14.84%), Marshallese (15.13%), and Samoan (18.89%). In each ethnicity from our population, the distributions of allele and genotype frequencies of the CYP2C19 *2 (rs4244285 G>A), *3 (rs4986893 G>A), and *17 (rs12248560 C>T) variants were significantly different from EUR.
The overall loss-of-function allele (A) frequencies of *2 (rs4244285 G>A) and *3 (rs4986893 G>A) were significantly higher in our population groups (25%-36% and 2.5%-10%, respectively) than EUR (15%, and 0%, respectively). In contrast, the overall increased function allele (T) frequencies of *17 (rs12248560 C>T) were significantly higher in EUR (22.5%) than in our population (1%-6%). In conclusion, our results are consistent with published reports of Asian populations are enriched with the reduced or loss of function alleles of CYP2C19 compared with EUR.
- Development of an online warfarin dosing platform using R programming language to facilitate healthcare professional duties and limit medication related errors. by Monther Alsultan [View Image]
Development of an online warfarin dosing platform using R programming language to facilitate healthcare professional duties and limit medication related errors.
Development of an online warfarin dosing platform using R programming language to facilitate healthcare professional duties and limit medication related errors.
Monther Alsultan, Joshua M. Morriss, Daniel Contaifer Jr, Suad Alshammari; Silas Contaifer, Rachel W Flurie, Dayanjan S. Wijesinghe#
Department of Pharmacotherapy and Outcome Sciences
Objective: 1) Gain experience in developing platform agnostic, fully operational and clinically relevant web applications for effective pharmacist led patient care. 2) Create a decision- support tool using open source software to facilitate evidence-based management therapy of warfarin in clinical settings where it is available for everyone to use at anytime and anywhere.
Introduction: Healthcare is continuously growing and modern technologies provide opportunities for the creation of effective tools to manage multiple diseases. Mobile devices such as smartphones enable easy access to a variety of websites remotely and make data and information readily available for use. Additionally, mobile devices can offer healthcare providers with fast and easy access to essential medical information to support patient care. The profession of pharmacy is fast changing from one primarily focused on dispensing medicinal goods to one intensely focused on the delivery of patient care. This has led pharmacists to be involved in a diverse clinical service such as patient's education, Medication Therapy Management (MTM) and medications dose adjustment. Implementing such services often place additional stress on the daily routine of pharmacists. Therefore, there is a high need to find efficient ways to support healthcare related clinical services. One of the widely used anticoagulant medications is warfarin. Warfarin has been available on the market as effective therapy in management of thrombotic disorders. However, warfarin is frequently associated with medications errors which may lead to serious adverse events. The purpose of this paper is to demonstrate this fact fully via warfarin dosing web application to help support healthcare professionals in clinical settings.
Methods: Open-source programming language R in conjunction with RStudio version 1.2.5033 were used to develop and implement our warfarin dosing platform. Shiny packages for R with other packages were used to create our platform as a web-based app. We based our calculations and function of our platform on the UW health warfarin management- adult- ambulatory clinical practice guidelines.
Results: The platform contains three tools users can use:1) Calculating the warfarin maintenance dose,2) Selecting INR goals and duration of therapy,3) Assessment of Bleeding risk. Additionally, the app has a hyperlink to direct the users to the resource used in this app. On the first page of the app, the user can select their INR target and input a patients INR and weekly dose. Then, the app will immediately display the results. On the second page of the app, there is a feature for users helps to choose the INR target recommended based on patient conditions; There is a drop down menu contains different type of antithrombotic indications. Additionally, on the third page of the app, there is a feature for users helps to calculate the bleeding risk using HAS-BLED score. The users can answer “Yes” or “No” on multiple risk factors to stratify patients’ risk into low, moderate or high.
Conclusion: Our warfarin dosing platform demonstrates the feasibility of creating a free-tool for healthcare professionals to facilitate their daily practice and potential for reducing medication related errors. Additionally, we demonstrate that pharmacists can take advantage of open-sources resources available to develop any health-related application suitable to their needs.
Future Directions: The skills gained in the implementation of this full stack web application development will be further improved upon to develop additional clinical support tools for pharmacists. Further implementations will also incorporate fully or partially trained machine learning models. Our ultimate goal is to allow pharmacists to utilize data driven decision making strategies to implement fast and effective patient care.
- Transcriptional Repressor Protein based Macrolide Biosensor Development with Improved Sensitivity by Jayani A. Christopher [View Image]
Jayani A. Christopher
Macrolide antibiotics are in high demand for clinical applications. Macrolides are biosynthesized via giant assembly line polyketide synthases (PKS) which are arranged in a modular fashion. Combinatorial biosynthetic methods have been used to produce diversified macrolides by reprograming these modules and modifying tailoring enzymes required for post synthetic modifications. However it is challenging due to the size and complexity of PKSs. To overcome this challenge, new enzymes for macrolide diversification could be obtained by directed evolution where a large number of enzyme variants need to be screened. Therefore it is important to develop high throughput screening methods to identify the enzyme variants. MphR is a promiscuous macrolide sensing transcriptional repressor protein which regulates a gene cassette where Green Fluorescence Protein (GFP) is expressed upon binding of the macrolide antibiotic ligand to MphR. A system of two plasmids contains the genes required for the sensing process. This research is basically an insight of improving the sensitivity of MphR biosensor using a gene knockout approach where a gene expressing a protein related to antibiotic resistance is knocked out from the E.coli chromosome to obtain higher sensitivity of the biosensor.
- World Wide Wake: A look into digital wake work in response to the murder of Breonna Taylor by KaLyn T. Coghill [View Image]
KaLyn T. Coghill
In Christina Sharpe's, In the Wake, she refers to "wake work" as conscious work. Wake work makes a conscious and intentional effort to celebrate one's life as they are passing and after they have transitioned on. Wake work includes grief, sadness, reminiscing, happiness, laughter, and many more emotions. We think of wake work happening in the physical, but I want to look at how weight work exists in the digital. This paper will discuss how wake work is done in digital spaces such as social media platforms. I will also be looking at how social movements such as black lives matter can act as a place for wake work to begin. I have created four sections that will talk about wake work in digital spaces. Hashtag activism, memorializing death, Fugitivity, and Black Dignity are ways that wake work is done in these virtual communities. I will investigate and provide examples of how each aligns with wake work, particularly to the death of Breonna Taylor.
- “Food is Last on My List”: Understanding Food Insecurity on an Urban College Campus by Kaija Craft, Jennifer Murphy, and Youngmi Kim [View Image]
Kaija Craft, Jennifer Murphy, and Youngmi Kim
Food insecurity among college students has become an increasing concern on campuses nationwide. The average rate of food insecurity among college students is estimated to be 32.9%, with students often experiencing the compounding effects of food, financial, and housing insecurities (Bruening et al., 2017; Leung et al., 2020). Furthermore, college students of traditionally marginalized racial groups, such as Black, Latino/a, and Native American students, are more likely to report experiencing food insecurity (Baker-Smith et al., 2020; El Zein et al., 2019). While there is a growing body of knowledge concerning quantitative data, qualitative research is needed to illuminate the full experience of college students living with food insecurity. This study aims to discover the barriers to food access, the impact of experiencing food insecurity, and coping strategies among college students. As part of a larger mixed-methods study, three focus groups were held at a large, urban university in the Southeastern United States. Findings present that barriers to food access included limited healthy options, limited kitchen access, a lack of transportation, insufficient time, and financial hardship. Students stressed the physical, mental, and emotional toll of living with food insecurity. Finally, various coping strategies were described, such as changes in eating habits, prioritizing other expenses, and participating in research. These findings contribute to the broader research on student basic needs and can help inform universities and policymakers to mitigate food insecurity on campus.
- COVID-10, Healthcare Interior Design + Provider Experience - How does your space work for you? by Ruth E.P. Deibler [View Image]
Ruth E.P. Deibler
The lack of research on healthcare staff experience and interior design of the spaces they work in is evident. A focus on staff perspective is needed, particularly staff who navigated the COVID-19 pandemic. This research seeks to capture those stories to develop further research in order to improve staff experience. The initial phase of this mixed-methods approach is a survey. Hypothetically, by placing providers at the center of qualitative research related to healthcare interior design, we can better understand existing healthcare spaces. Ideally, we can develop additional evidence-based, human-centered solutions to transform interior environments in healthcare.
The 20-year Women’s Health Study generated essential data on women’s health, but most importantly, the initial research has snowballed into 600+ research reports and continues to feed research that has made an indelible impact on women’s health (About the Women’s Health Study, n.d.).
In the same vein as the Women’s Health Study, this research documents provider experience with interior space and may lead to new healthcare design research. In the long term, the qualitative, grounded-theory approach may lead to remediation of our healthcare spaces by applying transdisciplinary design solutions developed through the research.
Grounded theory research “sets out to discover or construct theory from data” (Chun et al., 2008). This grounded-theory survey is entitled, “COVID-19, Healthcare Interior Design + Provider Experience – How does your space work for you?” Participants are providers working in any level of healthcare with any level of experience. The survey questions allow the provider to identify specific components of their space. Additionally, they were offered the opportunity to share a story about their relationship with their interior work environment during the COVID-19 pandemic. Healthcare staff’s ability to write about their interior environment experiences will offer additional clues about healthcare space and future research.
- Attitudes and Opinions About Direct-to-Consumer Genetic Testing in Undergraduate Science Students by Morgan N. Driver, Sally I-Chun Kuo, Olivia Nayeri, Chloe J. Walker, Chelsea Derlan Willians, Tricia Smith, Amy E. Adkins, and Danielle M. Dick [View Image]
Morgan N. Driver, Sally I-Chun Kuo, Olivia Nayeri, Chloe J. Walker, Chelsea Derlan Willians, Tricia Smith, Amy E. Adkins, and Danielle M. Dick
Background: There has been exponential growth in the number of direct-to-consumer genetic testing kits sold in the past decade. Consumers utilize direct-to-consumer genetic tests for a number of reasons which include learning about one’s ancestry and potential ways to manage health. Emerging adults tend to be early adopters of new technologies; however, there has been little research regarding the opinions about direct-to-consumer genetic testing in emerging adults.
Methods: Data came from a study conducted in an upper-level biology course focusing on understanding undergraduate science students’ overall experiences with receiving personalized genetic testing results from 23andMe. The present study used data collected at the baseline assessment which assessed their opinions and attitudes about direct-to-consumer genetic testing (N=133).
Results: Over 80% of participants would recommend direct-to-consumer genetic testing options including carrier status reports, DNA ancestry reports, wellness reports, and trait reports to others. However, participants were not as confident that others would be able to accurately interpret their test results. Additionally, more than two-thirds of the participants stated that they would ask a healthcare provider to help interpret their personalized genetic test results.
Conclusions: Participants lack confidence in both their ability to interpret their own results and others to interpret their results. It is important for direct-to-consumer genetic testing companies to educate consumers before providing results in order to minimize potential harms due to misinterpretation of results. Further research is needed to assess motivations to participate in direct-to-consumer genetic testing, impact of testing, and understanding of genetic testing results in emerging adults.
- The Critical Role of Dynamic Surface Tension of Surfactants on The Impact Dynamics of Water Droplets by Amir Esmaeili and Reza Mohammadi [View Image]
The Critical Role of Dynamic Surface Tension of Surfactants on The Impact Dynamics of Water Droplets
Amir Esmaeili and Reza Mohammadi
Due to their time-dependent surface tension, the addition of surface-active agents or surfactants to water for specific applications has made controlling the impact dynamics of these droplets a complex phenomenon. This work investigates the influence of the molecular weight, concentration, and ionic nature of the surfactants as well as the substrate surface characteristics on the impact dynamics of surfactant-laden droplets using a high-speed camera at 10000 frames per second. Sodium dodecyl sulfate, hexadecyltrimethylammonium bromide, and n-decanoyl-n-methylglucamine were used as anionic, cationic, and nonionic surfactants, respectively. We used hydrophilic glass slides, hydrophobic polytetrafluoroethylene, and superhydrophobic alkyl ketene dimer (AKD) as substrates. The results show that the efficiency of the surfactant addition in increasing the maximum spreading diameter is significantly influenced by the molecular weight and ionic nature of the solutions as well as the nonwettability of the substrate. Among all of the surfaces examined, the concentration and ionic nature of the solutions were found to be more dominant parameters in determining the energy dissipation in the retraction phase of the droplet impact on the superhydrophobic AKD surfaces. As the concentration decreases or positive charges are present in the solution, it is more likely to observe a similar retraction dynamic to pure water when the droplet hits the superhydrophobic AKD having negatively charged surface sites. Finally, in terms of the impact outcomes of the surfactant-laden droplets on the superhydrophobic AKD, it is shown that the influence of the surfactant addition is more noticeable at lower Weber numbers, where the droplet tries to rebound by overcoming the energy loss that occurred in the spreading.
- Selective GSK3B Deletion in Camk2a+ Forebrain Neurons or Inhibition Via Tideglusib, Decreases Ethanol Consumption in C57BL/6J Mice by Sam Gottlieb, Andrew D. van der Vaart, Brennen O'Rourke, and Michael F. Miles [View Image]
Selective GSK3B Deletion in Camk2a+ Forebrain Neurons or Inhibition Via Tideglusib, Decreases Ethanol Consumption in C57BL/6J Mice
Sam Gottlieb, Andrew D. van der Vaart, Brennen O'Rourke, and Michael F. Miles
Purpose: We previously identified glycogen synthase kinase-3 beta (Gsk3b) as a central member of a gene network highly regulated by acute ethanol in medial prefrontal cortex (mPFC) and associated with risk for alcohol dependence in humans. Further, we have demonstrated modulation of Gsk3b alters ethanol consumption in rodent models. GSK3B could thus represent a potential new therapeutic target for the treatment of alcohol use disorder (AUD). Here, we investigate the mechanisms of Gsk3b action in ethanol consumption and report preclinical evidence for the selective GSK3B inhibitor, tideglusib, as a therapeutic agent for AUD.
Methods: (1) Selective Cre-induced Gsk3b deletion in Camk2a-neurons within the forebrain using transgenic Camk2a-CreER/Gsk3b floxed mice bred with Gsk3b fl/fl mice to produce Cre/Gsk3b fl/fl mice, which were injected with tamoxifen to induce Gsk3b deletion or (2) selective pharmacological antagonism of GSK3B using Tideglusib delivered via gavage in a corn oil vehicle. Actions on drinking behavior were measured using mouse intermittent ethanol, two-bottle choice self-administration models in C57BL/6J mice.
Results: Deletion of Gsk3b in Camk2a-neurons decreased ethanol consumption and preference. There was no significant effects of sex or sex*genotype on either consumption or preference, so sexes were pooled. Gsk3b deletion did not alter basal locomotor activity, anxiety-like behavior (light-dark box), taste preference for quinine or saccharin, or ethanol pharmacokinetics. Initial administration of tideglusib (100mg/kg twice daily) or corn oil vehicle via gavage decreased total fluid consumption in all groups, regardless of ethanol drinking history or tideglusib treatment. However, following prolonged tideglusib, mice decreased binge (2hr) and daily (24hr) ethanol consumption and preference after three weeks of administration relative to vehicle controls. Tideglusib studies were only performed in male mice. Control studies showed no effect of tideglusib on liver fat accumulation in ethanol consuming animals. Ongoing work is assessing alternative oral tideglusib delivery methods in decreasing ethanol consumption.
Conclusion: These results suggest GSK3B may be a therapeutic target for treatment of AUD. Deletion of Gsk3b in forebrain Camk2a-neurons showed a regional and cell-type specificity in GSK3B’s modulation of ethanol consumption and preference, providing insight into the mechanisms of Gsk3b action in ethanol consumption. Targeting GSK3B using tideglusib, a selective GSK3B inhibitor, also produced a decrease in ethanol consumption and preference over water during the fourth week of treatment. These findings were consistent with previous work in our lab investigating the delivery of tideglusib through intraperitoneal injections, though these studies were limited to a shorter drug-administration period. Here we have used a more therapeutically translatable route of administration via oral gavage and begun to investigate the longer-term effects of tideglusib on ethanol behaviors and toxicity. Tideglusib is a clinically available agent that warrants investigation in the treatment of AUD.
Supported by NIAAA grants P50AA022537 and R01AA027581.
- Universal Design for Learning’s Successful Implementation: What Can Administrators Do? by Monica Grillo [View Image]
Administrators have a unique position to influence teacher attitudes by creating an inclusive school culture and providing instructional leadership. Implementing Universal Design for Learning (UDL) is a critical issue for public schools in our country. UDL is an inclusive framework based on the science of learning. It supports and removes barriers to learning for all students while maintaining high expectations. Federal education policies have called for inclusive instruction based on UDL principles. Nevertheless, our educators and administrators are not sure they believe in it and do not know what exactly it is or how to implement it with fidelity. Previous researchers have found that teachers are more likely to implement inclusive teaching practices such as UDL when they have positive attitudes toward them shaped by their culture, experiences, and training. UDL benefits all students‒not just those with unique needs‒by increasing student engagement and removing learning barriers.
- Influence of 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol preference and consumption in C57BL/6 male mice by Alaina M. Jaster, Sam Gottlieb, Michael Miles, and Javier González-Maeso [View Image]
Influence of 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol preference and consumption in C57BL/6 male mice
Alaina M. Jaster, Sam Gottlieb, Michael Miles, and Javier González-Maeso
Substance use disorders (SUD) account for a large number of mental health diagnosis in the United States and around the world. Approximately 13.6 million adults 26 or older and 5.1 million young adults (ages 18-24) battled with a SUD in 2017. Alcohol Use Disorder (AUD) alone effects nearly 6% of the adult population within the United States. This creates a substantial burden on the individual, with alcohol being the third-leading cause of preventable death in the United States. Few treatments for AUD exist, with no new FDA-approved therapeutic treatments within the last 15 years. Additionally, the limited treatments we do have are estimated to produce sustained abstinence in less than 20% of individuals. Psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and 2,5-dimethoxy-4-iodoamphetamine (DOI) affect processes related to cognition, perception and sensory processing. Recently, it has been demonstrated that serotonin 5-HT2A receptor agonists, such as psilocybin, can be useful in attenuating substance abuse. As an example, clinical findings have demonstrated the ability of psilocybin to decrease heavy drinking days in alcoholic heavy drinkers. Studies utilizing both rats and mice have also suggested the ability of DOI to decrease ethanol preference and consumption in a two-bottle choice paradigm of drinking behavior. The present study aimed to assess the ability of two acute doses of DOI (2 mg/kg and 5 mg/kg) on ethanol preference and consumption using the two-bottle choice paradigm. To test this, 15 adult male C57BL/6 mice were kept on a reverse light cycle and trained on the two-bottle choice procedure, in which they were allowed to drink for four weeks to obtain a baseline reading of drinking behavior. Following these four weeks, mice were assigned to either the treatment group or vehicle group based on weight and baseline drinking behavior. On the first day of the fifth and sixth weeks, mice were injected intraperitoneally with a dose of DOI or saline vehicle 30 minutes prior to access to 20% ethanol. The amount consumed of both water and ethanol on drinking days was measured at 2- and 24-hours and analyzed to calculate consumption and preference. Overall, our findings suggest that DOI did not affect ethanol consumption or preference at the 2- or 24-hour measures. The DOI-treated group showed no difference from the vehicle-treated group after receiving an either moderate (2 mg/kg) or high (5 mg/kg) dose of DOI. There was an overall interaction of time and treatment in both 2- and 24-hour fluid consumption in the groups. Further studies are warranted using DOI or other psychedelics and other paradigms for assessing drinking behavior to understand the effects of psychedelics in modulating substance use behavior.
- Validity of the Actigraph GT9X Accelerometer Step-Count Function in Adults with Heart Failure with Preserved Ejection Fraction by Jonathan D. Kenyon, Hayley Billingsley, Natalie J. Bohmke, Danielle Kirkman, Salvatore Carbone, and Youngdeok Kim [View Image]
Validity of the Actigraph GT9X Accelerometer Step-Count Function in Adults with Heart Failure with Preserved Ejection Fraction
Jonathan D. Kenyon, Hayley Billingsley, Natalie J. Bohmke, Danielle Kirkman, Salvatore Carbone, and Youngdeok Kim
Low physical activity is associated with heart failure with preserved ejection fraction (HFpEF). Step-counts, a measure of physical activity, can be measured via accelerometry. To date, few studies have examined validity of accelerometer-derived step-counts in the adults with HFpEF.
PURPOSE To assess criterion validity of the Actigraph GT9X accelerometer step-count function in adults with HFpEF via ankle, waist, and wrist placement, compared with manually counted, directly observed steps.
METHODS Six adults with HFpEF (age: 57.2 ± 9.4 y; African American: 50%; females: 100%) completed a cardiopulmonary exercise test (CPET) on a treadmill while wearing synchronized GT9X accelerometers on the ankle, waist, and wrist. Steps during CPET were measured by using the step-count function on the GT9X at 60 Hz sampling and data were downloaded into 1-second and 10-second epochs. Hand-tallied, directly observed steps (OS) was the criterion measure. Criterion validity was assessed via paired t tests to determine whether mean total steps (TS) from the three devices were significantly different from the mean TS from OS, and Pearson correlations were used to determine associations between device-measured TS and the total OS. Simple linear regression models were used to assess the effect of walking speed on absolute percentage error of the devices compared to OS. Agreement of the devices throughout the duration of the CPET was examined using Pearson correlations. Alpha was set at 0.05 for all statistical analyses.
RESULTS Mean TS from waist-worn (t = -5.29, p = .001) and wrist-worn (t = -12.50, p < .001) devices were significantly lower than mean TS from OS. Only TS from the ankle GT9X was significantly associated with TS from OS (r = 0.974, p = .001). GT9X-estimate steps from the ankle (r = 0.869, p < .001), waist (r = 0.550, p <.001), and wrist (r = 0.429, p <.001) were all significantly associated with OS-measured steps. Absolute percentage error was significantly and negatively associated with treadmill speed for devices on the ankle (b = - 10.70, p < .001), waist (b = -32.49, p < .001) and wrist (b = -10.08, p < .001).
CONCLUSION Our results suggest that accelerometer-derived TS may be a more accurate measure of TS when the device is worn on the ankle rather than waist or wrist, and that measurement error is higher at lower walking speed.
- Evaluating racial and ethnic disparities in access to primary care among gay and bisexual men in the US, a population at high-risk of HIV infection by Jessica S. Kiernan and April D. Kimmel [View Image]
Evaluating racial and ethnic disparities in access to primary care among gay and bisexual men in the US, a population at high-risk of HIV infection
Jessica S. Kiernan and April D. Kimmel
BACKGROUND: 69% of new HIV diagnoses in the US are among gay and bisexual men, with disparities by race and ethnicity. Primary care providers increasingly provide HIV prevention. Racial and ethnic disparities in primary care access are well-documented, but their persistence among gay and bisexual men is unknown. We examined racial and ethnic disparities in access to primary care among this population.
METHODS: We used nationally representative person-level sociodemographic, health status and utilization data, and data on organizational- and socially determinant barriers to care, from the National Health Interview Survey, 2013-2018. Outcomes were: 1) general physician visit
RESULTS: The sample included 1,867 gay and bisexual men (unweighted), 18-64 years with 28% NHB or Hispanic. NHB and Hispanic men were less likely have seen a general provider within the past 12 months (aOR=0.76, p=0.10) but the result was not significant with no difference in having a usual place of care (aOR=1.11, p=0.616). Findings were sensitive to the specification of primary care site as usual place of care.
CONCLUSIONS: Significant racial and ethnic disparities were observed when specifying a primary care specific site as place of care. Primary care engagement should be immediately prioritized to promote access and equity of HIV prevention.
- Mapping the VCU Campus Food Environment by Heather N. King, John C. Jones, and Dan J. Albrecht-Mallinger [View Image]
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.
- Activity of Saccharomyces cerevisiae by Single Entity Electrochemistry by John Lutkenhaus [View Image]
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.
- Influence of Telephone Preoperative Evaluations on Patient Medication Compliance on Day of Surgery by Emmanuel Magsino, Michael Jung, and Olga Suarez MD [View Image]
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.
- Vasculogenic Mimicry: Role of melanoma differentiation associated gene-9/syntenin by Jinkal Modi, Anjan Pradhan, Luni Emdad, Swadesh Das, and Paul Fisher [View Image]
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.
- Cost-effectiveness of Alternative HIV Testing Strategies among Hard-to-Reach Populations in East and Southern Africa. by Deo Mujwara and Deo Mujwara [View Image]
Cost-effectiveness of Alternative HIV Testing Strategies among Hard-to-Reach Populations in East and Southern Africa.
Deo Mujwara and Deo Mujwara
- Victimization and Psychological Wellbeing among Sexual and Gender Minority Emerging Adults: Testing the Moderating Role of Emotional Comfort from Companion Animals by Jennifer L. Murphy, Camie A. Tomlinson, Angela Matijczak, Kelly O'Connor, and Shelby McDonald [View Image]
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.
- Pharmacogenomics and SSRIs Appropriateness in Older Community Dwelling African Americans by Wint War Phyo, Lana Sargent, and Elvin T. Price [View Image]
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.
- Radiation Induces Metabolic Dysregulation in Pulmonary Fibroblasts by Josly Pierre-Louis, Margaret A. T. Freeberg, Jane K. Rebman, Thomas H. Thatcher, and Patricia J. Sime [View Image]
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.
- Device-Related Adverse Events From WATCHMAN FLX Implants As Reported By The Food And Drug Administration by Dongjin Suh BS, Paul Eugene Kim BS, Emmanuel Magsino BS, and Tae Shik Park [View Image]
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
- Carotid artery dissections from TCAR as reported by the Food and Drug Administration by Dongjin Suh BS, Yuchi Ma BS, Daniel H. Newton MD, Michael F. Amendola MD, and Kedar S. Lavingia MD [View Image]
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.