Research & Scholarship Showcase Book of Abstracts 2023
April 13, 2023
Research and Scholarship Showcase
(formerly Interprofessional Student Scholarship Showcase)
An annual event that showcases research and scholarship activities from health care programs across Manchester and Worcester campuses of Massachusetts College of Pharmacy and Health Sciences. This year thirty abstracts submitted by students, graduate students, and postgraduate residents and fellows were accepted and will be presented in a poster format.
Showcase Planning Committee Members:
School of Pharmacy, Worcester/Manchester
Matthew Metcalf and Alok Sharma (co-chairs)
Kaelen Dunican, Helen Pervanas, Holly Baker, Darlene DiTommaso, and Eva Shqina
New England School of Acupuncture, Worcester
Stephen Cina
School of Medical Imaging and Therapeutics, Worcester
Jeff Hill and Debra Crandell
School of Optometry, Worcester/Manchester
Kathryn Deliso
Forsyth School of Dental Hygiene, Worcester
Christine Dominick
School of Nursing, Worcester
Deirdre Donahue
School of Physical Therapy, Worcester
Christopher Joyce
School of Physician Assistant Studies, Worcester/Manchester
Linda Martino
School of Occupational Therapy, Manchester
Heidi Robertson
Abstract Title 1 Implementation and Outcomes of Blood Flow Restriction on Adults with Cerebral Palsy: a Case Series 2 College Students and Multiple Sclerosis: Developing a Toolkit for Academic Success 3 Peer Visitation for New Amputees: A Qualitative Study with Preliminary Findings and Benefits 4 RPMI 8226 LE Enhanced Targeting, Extracellular LDH release & Cytotoxicity of Liposomal Therapeutics against Multiple Myeloma 5 The Novel Uses of Ketamine 6 Phosphodiesterase 5 (PDE-5) Inhibitors and Alzheimer’s Disease 7 Usability and Usefulness Fact Sheets to Promote Best Practice in Pediatric Physical Therapy 8 Discovery of Novel HIV-1 Protease Inhibitor Analogs by Computational Methods and Pharmacophore Hypothesis 9 Systematic Review and Bayesian Network Meta-Analysis of SodiumGlucose Co-Transporter 2 (SGLT2) Inhibitors on Cardiovascular Outcomes 10 Developing a Guide for Rehabilitation for Physical Therapists Working with Adolescents with High-Functioning Autism 11 Identifying Baseball Pitchers at Risk for Arm Injuries Using Standard Shoulder Strength and Range of Motion Measures 12 Evaluating Novel Lipid Extract-Modified Nanoliposomes for Retinoblastoma Treatment Using Y79 Cell Model and CCK-8 In-vitro Cytotoxicity Assay 13 A Review of Interprofessional Collaborative Practice and Educational Strategies in Physical Therapy Clinical Practice Settings 14 Development of a Plant-based Drug Assay Using Visualization of Chemonastic Responses 15 Grape Extract Toxicity in MDCK Cells 16 Evaluation of the Penetration of Topical Retinol Products into the Skin 17 Feasibility of Robot-Assisted Remote Lung Ultrasound Imaging
Table of Contents
Abstract Title
18 Selectivity of SK-N-DZ Lipid Extract-Modified Nanoliposomes for Targeted Delivery to Neuroblastoma
19 Investigating the Effects of Manual Therapy on Pain Processing and Modulation: A Scoping Review
20 Effectiveness of Pharmaceutical Care Curriculum on Improving Students Abilities to Communicate with the Deaf/Hard of Hearing Population to Increase Patient Outcomes
21 Improving Chagas Disease Treatment using a Pyridinyl Pyrazole Scaffold
22 Gamification of Learning for the Purposes of Pharmacy Education: Piloting a Pharmaceutical Industry Role-Playing Game
23 Expressions of Platelet, Drug Metabolism, and Vitamin D Receptor Pathway Genes are Dysregulated between Early Stage and Advanced Stage Breast Cancer in Younger Patients
24 Synthesis of New Antimalarial Drugs in the Age of Resistance
25 Visual Comparison of Chemonastic Responses in Two Plant Species Across Different Time Scales. Development of a Plant-Based Alternative to Animal Drug Testing
26 The Quality of Life and Gene Expression Profiles of Pancreatic Cancer Patients: Ex-Cigarette Smokers Against Never Smokers
27 The Evaluation of Diuretic Patterns in Hospitalized Heart Failure Patients in a Rural Academic Medical Center in Northern New England
28 Optimization and Evaluation G401-CLENs for Enhanced Targeting of Rhabdoid Tumors
29 Piperlongumine Reverses EGFR Resistance as an Adjuvant Treatment in Lung Cancer Cells
30 Polycystic Ovarian Syndrome (PCOS) and Conception
Table of Contents - Continued
Abstract: 1
Implementation and Outcomes of Blood Flow Restriction on Adults with Cerebral Palsy: a Case Series
Author(s): Christopher Joyce, Brendan Aylward, Nicholas Rolnick, Steven Lachowksi, Brittany Polk, Amber Wright, Michael Peysaknov, Mairead O'Sullivan, Amanda Donahue, Jessica, Lucas, Hannah, Tavares, and Yusheng, Chen
Faculty Advisor/Principal Investigator: Christopher Joyce
Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: The purpose of this case series was to examine changes in hypertrophy, strength, and endurance, and describe the safety, feasibility, and acceptability of BFR in adults with CP.
Description/Methods/Materials: Three male participants with GMFCS Level 3 CP were invited to participate. Novel leg press and leg extension exercises were adapted to physical limitations. A periodized 8-week BFR protocol progressed the participants through 4 sets of varying repetition schemes at 20%-25% 1RM using a limb occlusion pressure of 60%, 70%, and then 80% for weeks 1, 2, and 3-8, respectively. Outcomes: Hypertrophy via ultrasonographic cross-sectional area of vastus intermedius (VI-CSA), rectus femoris (RF-CSA), and biceps femoris (BF-CSA; Strength via 3-rep max in the leg press (LP-3RM) and knee extension (KE-3RM), as well as dynamometry knee extension (KEHHD) and flexion (KF-HHD); Endurance via 30-second Sit to Stand Test (30CST); Safety via BP during, and post-BFR and adverse event tracking; Feasibility via number of people and time duration of BFR exercises; Acceptability via rate of perceived discomfort (RPD) (0-10) following each exercise and qualitative interviews at the end of the study.
Results & Conclusion/Discussion: All participants completed 16 visits with no adverse events. Results are presented as change scores for Participants 1, 2, and 3, respectively. Hypertrophy(mm). Right VI-CSA: –0.8, -0.9, -2.9; Left VI-CSA: +1.2, +0.3, +1.0; Right RF-CSA: +0.2, -1.1, -3.6; Left RF-CSA: +3.0, -1.9, +0.7; Right BF-CSA: –2.3, -1.2, -7.7: Left BF-CSA: 0.0, +5.2, -7.1. Strength(lbs) and Endurance. LP-3RM: +50, +30, -30; KE-3RM Right and Left: +5, +7.5, +10; Right KE-HHD: –6.5, +10.9, -6.1; Left KE-HHD: +0.8, +9.0, -4.0; Right KF-HHD: -3.6, +1.8, +5.4; Left KF-HHD: +3.4, +7.5, -4.4. 30CST: 0, +4, +5, reps. Safety. BP never exceeded predefined safety cut-offs. Feasibility. Duration of BFR exercises when BP was taken averaged 45 minutes and reduced to 20 minutes once BP readings stopped. One team member handled all exercise and BFR management while another collected data. Acceptability. Mean RPD was 5.8. Qualitative data will be thematically analyzed. All participants completed 16 visits with no adverse events. Results are presented as change scores for Participants 1, 2, and 3, respectively. Hypertrophy(mm). Right VI-CSA: –0.8, -0.9, -2.9; Left VI-CSA: +1.2, +0.3, +1.0; Right RF-CSA: +0.2, -1.1, -3.6; Left RF-CSA: +3.0, -1.9, +0.7; Right BF-CSA: –2.3, -1.2,7.7: Left BF-CSA: 0.0, +5.2, -7.1. Strength(lbs) and Endurance. LP-3RM: +50, +30, -30; KE-3RM Right and Left: +5, +7.5, +10; Right KE-HHD: –6.5, +10.9, -6.1; Left KE-HHD: +0.8, +9.0, -4.0; Right KF-HHD: -3.6, +1.8, +5.4; Left KF-HHD: +3.4, +7.5, -4.4. 30CST: 0, +4, +5, reps. Safety. BP never exceeded predefined safety cut-offs. Feasibility. Duration of BFR exercises when BP was taken averaged 45 minutes and reduced to 20 minutes once BP readings stopped. One team member handled all exercise and BFR management while another collected data. Acceptability. Mean RPD was 5.8. Qualitative data will be thematically analyzed.
Implications/Clinical Relevance: BFR may be an effective means to increasing strength in adults with CP who cannot tolerate high intensity resistance training.
Abstract: 2
College Students and Multiple Sclerosis: Developing a Toolkit for Academic Succes
Author(s): Annalise Lowy, Andrew Faria, Kirsten Sjogren, Cameron Watson, and Erin Faraclas Faculty Advisor/Principal Investigator: Erin Faraclas
Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: The purpose of this implementation research is to develop an evidence based toolkit for college students with Multiple Sclerosis. The specific aims include, (1) Identify and describe challenges college students with MS face and (2) develop tools and resources to facilitate a successful college experience.
Description/Methods/Materials: This study used the Re-AIM framework to guide the establishment and implementation of the toolkit. A scooping review of relevant evidence, followed by document and article analysis informed the toolkit development. Upon creation of the toolkit dissemination of the toolkit through a college resource center has been established. Future evaluation of the toolkit will occur as adoption of the toolkit occurs.
Results & Conclusion/Discussion: College students with MS face a host of symptoms and impairments that can impact their higher education success. Review of the evidence based literature revealed physical limitations, fatigue, vision, slowed processing, heat sensitivity, bowel/bladder difficulties, and depression as factors having an impact of higher education success for people with MS. In addition, college students with MS may be unaware of how to access or request accommodations in the college setting. The resulting toolkit for this population includes resources and information specific to the unique challenges MS can cause in the college setting. College students with MS face a host of symptoms and impairments that can impact their higher education success. Review of the evidence based literature revealed physical limitations, fatigue, vision, slowed processing, heat sensitivity, bowel/bladder difficulties, and depression as factors having an impact of higher education success for people with MS. In addition, college students with MS may be unaware of how to access or request accommodations in the college setting. The resulting toolkit for this population includes resources and information specific to the unique challenges MS can cause in the college setting.
Implications/Clinical Relevance: According to the National Multiple Sclerosis Society (NMSS), Multiple Sclerosis (MS) is an autoimmune disease in which the immune system targets its own central nervous system, specifically myelinated nerve cells. Over time damage and scarring to the nerves occurs that disrupts transmission of nerve impulses.1 MS impacts each person differently because the location and amount of the lesions are unpredictable. This variability causes a wide variety of symptoms and presentations to occur. A common initial presentation is vision disturbances due to lesions in the optic nerve, but other symptoms include weakness/fatigue in 7581% of cases, loss of balance or dizziness in 70% of cases, 65% experience numbness, 50% depression, and 50% experience mobility issues.2 Recently, rates of MS overall have increased from 123,000 in 1980 to 400,000 in 2012, and today 1 million Americans live with MS.3 Advances in early detection of MS have resulted in diagnosis at younger ages. Diagnosis of MS in younger adult and even pediatric populations have been increasing, but research and literature has not kept up with this increase in population demographics.4 This younger age at diagnosis highlights a need for better understanding of how multiple sclerosis impacts students, especially college students that may be advocating for themselves for the first time.
Abstract: 3
Peer Visitation for New Amputees: A Qualitative Study with Preliminary Findings and Benefits
Author(s): Anders Lafortune, Brittany Leung, Harsh Patel, Kristine Richard, and Bruce Elliott
Faculty Advisor/Principal Investigator: Bruce Elliott
Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: The purpose of this study is to examine the reports of peer visitors regarding their personal experiences related to providing peer support to fellow amputees. As a result, this study provides information to better understand the impact of post-amputation peer visitation programs on perceived health-related outcomes, and ultimately for peer visitation to be implemented in the plan of care for those who have experienced amputation surgery.
Description/Methods/Materials: Through purposeful sampling, 10 subjects were selected to participate in this study. The primary data collection tools for this investigation were in-depth, audiotaped interviews along with a pre-interview questionnaire. An open-ended questionnaire was used for data collection during the interview process. Each interview was recorded and transcribed for future coding and analysis. The transcribed interviews were analyzed to get a general impression of the content and a list of themes was compiled.
Results & Conclusion/Discussion: The following themes were identified through data analysis: providing real life examples and improving participants network of social support, importance of mindset and getting back to a sense of normalcy, peer visitor’s emotional attachment, having good/helpful training, importance of a balanced relationship, and the desire to give back. The following themes were identified through data analysis: providing real life examples and improving participants network of social support, importance of mindset and getting back to a sense of normalcy, peer visitor’s emotional attachment, having good/helpful training, importance of a balanced relationship, and the desire to give back.
Implications/Clinical Relevance: This study equips healthcare providers and recent amputees with a greater understanding of the impact of peer visitation on health-related outcomes post-amputation. These preliminary findings indicate the need for more research to further increase awareness on the benefits and importance of implementation of peer visitation.
Abstract: 4
RPMI 8226 LE Enhanced Targeting, Extracellular LDH release & Cytotoxicity of Liposomal Therapeutics against Multiple Myeloma
Author(s):
Matthew Amorin, Peter Daley, William Smullen, and Robert Campbell Faculty Advisor/Principal Investigator: Robert Campbell
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Multiple Myeloma (MM) is a hematologic disease that originates in the bone marrow from tumorigenic plasma cells. Due to the enhanced anaerobic metabolism of cancer cells, elevated media levels of LDH (lactate dehydrogenase) following cell death serves as a reliable indicator of MM treatment efficacy. Cell membrane Lipid-Extracted Nanoliposomes (CLENs) are novel drug delivery vehicles demonstrating preferential uptake by breast cancer cells. The lipid extracts (LE) derived from MM cells might well improve drug targeting to MM cells as well. This study thus evaluates whether LE derived from MM cells can be employed to improve formulation and cellular properties of liposome therapeutics.
Description/Methods/Materials: The RPMI 8226 cell line was the cellular model for MM. Cells were seeded at 10,000 cells/mL in 48 well plates for cytotoxicity studies. Non-target Y79 (retinoblastoma), U937 (lymphoma) cells, and off-target healthy peripheral blood mononuclear cells (PBMCs) served as the cellular controls for this study. Rhodamine-labeled liposome preparations were employed for cellular binding studies with cells seeded at 20,000 per mL of growth media. Cells were incubated at 37°C with gentle agitation between 0 and 60 minutes. For cytotoxicity, cells were exposed to two different drug-loaded liposome preparations, a MM targeted preparation consisting of 95% DOPC and 5 mol% RPMI-8226 cell lipid extract (DOPC/LE 95/5) and a non-specific, 100% DOPC liposome control. Liposomes were loaded with three different drugs (carboplatin, doxorubicin, and gemcitabine) at a drug-to-lipid ratio of 3 mol%. Drug-loaded vesicle preparations were separated from free drug by centrifugation and overnight dialysis. The CyQUANTTM LDH Cytotoxicity Assay was utilized to assess extracellular LDH activity and cytotoxicity.
Results & Conclusion/Discussion: The mean diameter for the DOX-loaded DOPC (100%) and DOPC/LE (95/5) nanoliposomes was 203 ± 24.3 nm (n=4) and 235 ± 24.6 nm (n=4), respectively. The average zeta potential for the two preparations ranged from slightly negative to electroneutral for LE-modified liposomes and DOPC controls, respectively. Following overnight exposure of target cell line RPMI 8226 to drug-loaded DOPC (100%) and drug-loaded DOPC/LE (95/5), the inclusion of LE significantly improved the cytotoxicity of all three drugs. However, there was no difference in cytotoxicity between the two drug-loaded liposome preparations against non-target Y79 cells. For the PBMCs, LE reduced carboplatin cytotoxicity (at 75 nM), doxorubicin (at 75 and 150 nM), and gemcitabine (at 150 nM). Initial liposomal binding studies indicate that the inclusion of LE significantly improves cell binding interaction compared to DOPC (100%) at all time points. For negative control cell lines, the inclusion of LE decreased binding and uptake by Y79, U937, and for PBMCs. The mean diameter for the DOX-loaded DOPC (100%) and DOPC/LE (95/5) nanoliposomes was 203 ± 24.3 nm (n=4) and 235 ± 24.6 nm (n=4), respectively. The average zeta potential for the two preparations ranged from slightly negative to electroneutral for LE-modified liposomes and DOPC controls, respectively. Following overnight exposure of target cell line RPMI 8226 to drugloaded DOPC (100%) and drug-loaded DOPC/LE (95/5), the inclusion of LE significantly improved the cytotoxicity of all three drugs. (Abstract truncated at 500 words)
Abstract: 5
The Novel Uses of Ketamine
Author(s): Ida Salehi, Parivash Asadnejad, and Michael Bear Faculty Advisor/Principal Investigator: Michael Bear Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, and a safe dissociative anesthetic that has been used for both the induction and maintenance of anesthesia for more than forty years. As a rapid acting tranquilizer, ketamine is used liberally in veterinary medicine and has been used for its analgesic and anti-inflammatory properties in humans for decades. There is a recent growing interest in exploring other uses of ketamine in humans due to its relatively safe cardiovascular and respiratory profile. Our goal is to review the novel uses of ketamine in the field of psychiatry and neurology.
Description/Methods/Materials: The novel uses of ketamine were identified by researching ketamine’s indications of drug reference resources such as DynaMed and Lexicomp. Three new conditions which ketamine showed to be effective for were Post-Traumatic Stress Disorder (PTSD), and Major Depressive Disorder (MDD).
The PubMed database (1946 – September 30, 2022) was searched using MeSH terms and keywords ketamine, PTSD and MDD combined using Boolean operators AND and OR. After limiting the search to randomized controlled trials, meta-analysis and systematic reviews, 41 initial results were identified. 22 articles resulted from further narrowing down to the studies which were published from January 1, 2021, to September 30, 2022. Only 9 relevant articles that addressed the effect of ketamine on PTSD and MDD were used to conduct this review.
Results & Conclusion/Discussion: PTSD: Intravenous bolus and continuous infusions of ketamine were the most studied routes of administration to treat PTSD. Studies showed mixed effects on PTSD; some studies associated ketamine with improving the symptoms of chronic PTSD, while others showed no effects on the initial stages of this disorder. When compared to ketamine’s effects on healthy subjects, it did not cause cognitive dysfunction among patients with PTSD.
MDD: Esketamine and its racemic mixture, ketamine, have shown promising antidepressant effects in patients with MDD following repeated intranasal administration or after intravenous infusion. The most common adverse drug effects associated with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia, sedation, and paresthesia. PTSD: Intravenous bolus and continuous infusions of ketamine were the most studied routes of administration to treat PTSD. Studies showed mixed effects on PTSD; some studies associated ketamine with improving the symptoms of chronic PTSD, while others showed no effects on the initial stages of this disorder. When compared to ketamine’s effects on healthy subjects, it did not cause cognitive dysfunction among patients with PTSD.
MDD: Esketamine and its racemic mixture, ketamine, have shown promising antidepressant effects in patients with MDD following repeated intranasal administration or after intravenous infusion. The most common adverse drug effects associated with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia, sedation, and paresthesia.
Implications/Clinical Relevance: New indications for an existing drug agent.
Abstract: 6
Phosphodiesterase 5 (PDE-5) Inhibitors and Alzheimer’s Disease
Author(s): Ida Salehi and Donna Bartlett
Faculty Advisor/Principal Investigator: Donna Bartlett
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: To explore the recently published studies focused on the effects of PDE5inhibitors and their effectiveness in the treatment of Alzheimer’s disease (AD). Limitations of the existing US Food and Drug Administration-approved agents for treating AD such as cost, non-reliable efficacy, and dose-dependent side effects led to conducting this review. Because of insufficient evidence on modifying the expression of AD, the standard pharmacotherapeutic treatment (cholinesterase inhibitors) has limited use. Memantine, a glutamate regulator, has shown fewer side effects. The available therapeutic agents, though effective in neurotransmitter production can cause oxidative stress, dysfunction of the neuronal tissue, and apoptosis.
Description/Methods/Materials: The PubMed database was searched using the keywords “PDE5 inhibitors,” “phosphodiesterase 5 inhibitors,” and “Alzheimer’s disease.” After limiting the results to studies published from January 1, 2020, to May 31, 2022, eight articles were identified; those that investigated the effects of PDE 5 inhibitors and cognitive function were included. Additionally, the findings in a comprehensive systematic review published in 2020 were referenced to compare the recent findings to what had been discovered prior to 2020.
Results & Conclusion/Discussion: PDE-5 proteins are found in the cytoplasm of large human neuronal cells, especially in the cortex and hippocampus. Their inhibitors can prevent neurodegeneration by interfering with several pathways: increasing the concentration of cGMP, affecting nitric oxide levels in the central nervous system, and improving blood flow to the brain. Promising outcomes from animal studies show sildenafil effects on oxidative stress in the brain tissues in AD-induced rats have shown decreased superoxide dismutase, reduced glutathione, increased malondialdehyde, and total nitrite/nitrate (P < 0.0001) were statistically significant compared with the control group. PDE-5 proteins are found in the cytoplasm of large human neuronal cells, especially in the cortex and hippocampus. Their inhibitors can prevent neurodegeneration by interfering with several pathways: increasing the concentration of cGMP, affecting nitric oxide levels in the central nervous system, and improving blood flow to the brain. Promising outcomes from animal studies show sildenafil effects on oxidative stress in the brain tissues in AD-induced rats have shown decreased superoxide dismutase, reduced glutathione, increased malondialdehyde, and total nitrite/nitrate (P < 0.0001) were statistically significant compared with the control group.
Implications/Clinical Relevance: New indication for an existing agent
Abstract: 7
Usability and Usefulness Fact Sheets to Promote Best Practice in Pediatric Physical Therapy
Mary Campbell, Brianna Leporati, Connor Lockyer, Megan Williams, Madalynn Wendland, and Danielle Bellows
Author(s):
Faculty Advisor/Principal Investigator: Danielle
Bellows
Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: Pediatric physical therapists (PTs) and assistants (PTAs) need ready access to the best available synthesized evidence to inform practice. The Academy of Pediatric Physical Therapy (APTA Pediatrics) has supported dissemination of fact sheets since 2006 as a tailored intervention to meet this need, but the program has never been evaluated. This administrative case report describes the assessment of, utilization, usability, and usefulness of APTA Pediatrics fact sheets.
Description/Methods/Materials: APTA Pediatrics Fact Sheet Committee, established in April 2020, has an overarching vision to maintain a repository of up-to-date fact sheets on relevant topics to enhance awareness and knowledge of the best available evidence. Committee members assist authors with fact sheet production and recommend dissemination strategies to APTA Pediatrics leaders. To inform this work a 32-item survey was distributed from February to April 2021 through APTA Pediatrics website and social media accounts using a snowball sampling technique. Anonymous responses about fact sheet content, access, usability, and usefulness were collected via Likert scale, ranking, and open response items. One hundred ninety-six pediatric PTs representing a variety of practice settings completed the survey. No PTAs participated. Quantitative data were analyzed using descriptive statistics and open responses were analyzed using content analysis.
Results & Conclusion/Discussion: Overall, PTs described fact sheets as a useful, informative, succinct resource they would seek out in the future. The most common reasons for accessing fact sheets were to share knowledge about pediatric conditions and as a starting point for evidenceinformed patient care. Important characteristics included brief evidence synthesis, visual presentation of information, algorithms or decision aids, and references. Challenges with searching for topics, lack of translation into other languages, timeliness of revision, variable organization of information, and limited caregiver fact sheets were identified as areas for improvement. Overall, PTs described fact sheets as a useful, informative, succinct resource they would seek out in the future. The most common reasons for accessing fact sheets were to share knowledge about pediatric conditions and as a starting point for evidence-informed patient care. Important characteristics included brief evidence synthesis, visual presentation of information, algorithms or decision aids, and references. Challenges with searching for topics, lack of translation into other languages, timeliness of revision, variable organization of information, and limited caregiver fact sheets were identified as areas for improvement.
Implications/Clinical Relevance: N/A
Abstract: 8
Discovery of Novel HIV-1 Protease Inhibitor Analogs by Computational Methods and Pharmacophore Hypothesis
Author(s): Sumin Kim, Ellie D Solitro, and Carolyn Friel
Faculty Advisor/Principal Investigator: Carolyn Friel
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: To successfully design a novel HIV-1 protease inhibitor analog that is both safe and effective for the treatment of HIV disease.
Description/Methods/Materials: The binding site of HIV-1 protease was defined using FRED Receptor. Nelfinavir ligand was extracted from complex 2R5Q using Pymol software and was optimized and then docked into the active site of HIV-1 protease. Conformers of nelfinavir in the active site were generated and Chemgauss3 score was obtained. The Total Score from Chemguass3 of nelfinavir and its interaction with the receptor were used as the comparator for evaluation of the new analogs. Analog1 was designed by generating a library of nelfinavir analogs via vBrood. Analog2 was designed based on the structure of nelfinavir and the 3-D pharmacophore. To measure the affinity of the analogs to the active site HIV-1 protease, FRED command prompt was used in OpenEye Commend so the ligand-receptor interactions were analyzed in VIDA.
To quantify the safety of the analogs, StarDrop was used. Using the QSAR models of seven key toxicity endpoints, the analogs were computed to predict the EC50 and IC50. To characterize further pharmacokinetic properties of the analogs, the library was made by collecting chemical and biological properties of ten comparator compounds from FDA drug labels; saquinavir, indinavir, ritonavir, lopinavir, tipranavir, amprenavir, atazanavir, danrunavir and nelfinavir. The two analogs were then computed again to predict other properties, such as solubility (logS), HIA, P-gp transport, hERG affinity (pIC50), CYP2D6 affinity (pKi) and more.
Results & Conclusion/Discussion: Two analogs were successfully designed. Both analogs showed overall better pharmaceutical properties than nelfinavir. Analog 1 had a significant improvement on Chemgauss3 Total Score (-76.37), indicating a higher affinity to the receptor than to nelfinavir (61.39). Analog 1 formed more hydrophobic interaction and hydrogen bond with the receptor protein at the three out of four binding pockets. The molecular weight of Analog 1 (MW=558.8) was smaller than nelfinavir (568.79), implying the possibility of crossing the cell membrane more readily than nelfinavir. Analog 2 also showed improved binding affinity compared to nelfinavir with an estimated log P around 4, with potential to be administrated orally. Analog 2 and HIV-1 protease demonstrated improved interaction with receptor than nelfinavir. Both analog 1 and analog 2 were confirmed through SciFinder search to be novel derivatives of nelfinavir that have not yet been discovered or studied. Two analogs were successfully designed. Both analogs showed overall better pharmaceutical properties than nelfinavir. Analog 1 had a significant improvement on Chemgauss3 Total Score (-76.37), indicating a higher affinity to the receptor than to nelfinavir (-61.39). Analog 1 formed more hydrophobic interaction and hydrogen bond with the receptor protein at the three out of four binding pockets. The molecular weight of Analog 1 (MW=558.8) was smaller than nelfinavir (568.79), implying the possibility of crossing the cell membrane more readily than nelfinavir. Analog 2 also showed improved binding affinity compared to nelfinavir with an estimated log P around 4, with potential to be administrated orally. Analog 2 and HIV-1 protease demonstrated improved interaction with receptor than nelfinavir. Both analog 1 and analog 2 were confirmed through SciFinder search to be novel derivatives of nelfinavir that have not yet been discovered or studied. (Abstract truncated at 500 words)
Abstract: 9
Systematic Review and Bayesian Network Meta-Analysis of Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors on Cardiovascular Outcomes
Author(s): Rachna Sharma, Dhaval Mandli, and Matthew Silva
Faculty Advisor/Principal Investigator: Matthew Silva
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Evaluate cardiovascular outcomes observed using available sodium-glucose cotransporter 2 inhibitors (SGLT2i) in long-term clinical trials: 1) CANagliflozin CardioVAScular Assessment Study (CANVAS) Program; 2) Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE); 3) EMPAgliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), 4) Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) and 5) Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes (VERTIS CV).
Description/Methods/Materials: A systematic review and literature search prioritizing randomized controlled trials in human subjects with diabetes and cardiovascular disease at high risk for cardiovascular events was done in PubMed using the generic drug names canagliflozin, empagliflozin, dapagliflozin and ertugliflozin. Inclusion criteria were cardiovascular outcome trials of two years or longer in duration. Outcomes include all cause mortality, cardiovascular (CV) death, myocardial infarction (MI), stroke, serious adverse events and combinations of CV death and MI and CV death, MI and stroke. Frequentist and Bayesian network meta-analysis was used to compare direct pair-wise evaluations of active treatment against placebo and indirectly using Bayesian network analysis. Odds ratio and the random effects model was used, data were represented as point estimates and 95% confidence intervals. Surface Under the Cumulative RAnking (SUCRA) values were used to determine the likelihood that a treatment would reduce outcomes, allowing for a ranking order of 1-5 (1=best, 5=least). Treatments ranked 1 and 2 were determined to be the most clinically useful.
Results & Conclusion/Discussion: There were 773 relevant articles identified resulting in eight fulltext reviews and five original reports. Pair-wise evaluations of all-cause mortality and cardiovascular death found no difference between active treatment and placebo using random effects models.
Empagliflozin and canagliflozin protected against all-cause mortality [0.67 (0.55-0.81); 0.86 (0.760.98)] and cardiovascular mortality [0.61(0.49-0.77); 0.85 (0.73-1.0)] compared to placebo in the frequentist analysis. No treatment was consistently better than placebo or compared to other treatments in the Bayesian analysis. Canagliflozin, empagliflozin and dapagliflozin protected against cardiovascular death, MI and stroke in the frequentist model [0.82(0.74-0.91; 0.85(0.73-0.99); 0.92(0.84-1.00)] compared to placebo, however, not in the Bayesian model. Empagliflozin (91%) and canagliflozin (59%) were ranked first and second respectively for the reduction of all-cause mortality and cardiovascular death in the Bayesian analysis. Canagliflozin (87%) and empagliflozin (58%) were ranked first and second respectively for the reduction of cardiovascular death and hospitalization; CV death, MI and stroke (82%, 70%) and serious adverse events (80%, 71%). Canagliflozin (80%) and dapagliflozin (67%) were ranked first and second for reduction of myocardial infarction. The net ranking suggests the following prioritization according to SUCRA values: anagliflozin> empagliflozin> dapagliflozin> ertugliflozin> placebo. There were 773 relevant articles identified resulting in eight full-text reviews and five original reports. Pair-wise evaluations of allcause mortality and cardiovascular death found no difference between active treatment and placebo using random effects models. Empagliflozin and canagliflozin protected against all-cause mortality [0.67 (0.55-0.81); 0.86 (0.76-0.98)] and cardiovascular mortality [0.61(0.49-0.77); 0.85 (0.73-1.0)] compared to placebo in the frequentist analysis. (Abstract truncated at 500 words)
Abstract: 10
Developing a Guide for Rehabilitation for Physical Therapists Working with Adolescents with High-Functioning Autism
Author(s): Milad
Kinsey, Ashley Feather, Daniel Florendo, and Elizabeth Fuller Faculty Advisor/Principal Investigator: Elizabeth Fuller
Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: Currently, there is a limited amount of research and resources for physical therapists on how to treat those with ASD. The purpose of this project is to gather research to create an educational module that would be given to new upcoming physical therapists to better understand what factors they need to be aware of when working with the adolescent ASD population. This will provide therapists with a resource on how to treat those with ASD and increase the quality of care.
Description/Methods/Materials: A literature review was conducted to create an educational module based on the review of 15 wide-ranging pieces of literature including pilot studies, systematic reviews, double-blind studies, and interviews. The literature reviewed looked at the diagnosis of ASD, how other medical professionals have attempted to create a better environment to treat this population, and other topics on how to work with adolescents with ASD. A survey that can be handed out at the end of the presentation will be used to evaluate whether the key points of the educational module were presented clearly and if the information was useful.
Results & Conclusion/Discussion: Currently there is no agreed upon definition of ASD creating ambiguity in how it is viewed. The analysis and comparison of many factors such as movement, motor development, apraxia, and motor learning do not use the same vocabulary across different professional fields. The non-standardization of these aspects makes it difficult to communicate between providers and may also add anxiety for the patient and their families. It has been shown across multiple studies that healthcare providers are not being trained to work with this specific population.
Currently there is no agreed upon definition of ASD creating ambiguity in how it is viewed. The analysis and comparison of many factors such as movement, motor development, apraxia, and motor learning do not use the same vocabulary across different professional fields. The nonstandardization of these aspects makes it difficult to communicate between providers and may also add anxiety for the patient and their families. It has been shown across multiple studies that healthcare providers are not being trained to work with this specific population.
Implications/Clinical Relevance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects communication and behavior. ASD has an incidence of about 110 per 10,000 and is characterized by limitations in a person’s social interactions, communicative skills, restricted interests, and stereotyped or repetitive behaviors. ASD has different levels of severity ranging from individuals who are independent with activities of daily living to those who require significant support throughout their day. As a result of these characteristics individuals with ASD face barriers when it comes to accessing healthcare. By educating physical therapists they will better understand the barriers that adolescents with ASD face in the healthcare system. With this education, clinicians will have the knowledge to provide a better experience for this population when they come to physical therapy. This education will also help increase confidence in treating and working with these patients to create an overall better healthcare experience for the patient and clinician.
Abstract: 11
Identifying Baseball Pitchers at Risk for Arm Injuries Using Standard Shoulder Strength and Range of Motion Measures
Author(s): Hayden Gray, Gregory Oreste, Daniel Saggal, Anthony Videtto, and Janna KucharskiHoward
Faculty Advisor/Principal Investigator:
Janna Kucharski-Howard Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: The purpose of this study was to identify collegiate baseball pitchers at risk for injury by assessing their shoulder strength and range of motion (ROM). Our hypothesis was that these two variables do not predict injury in baseball pitchers.
Description/Methods/Materials: Shoulder strength and range of motion measurements were taken on 21 Division I collegiate baseball pitchers before the 2022 baseball season. External rotation (ER) and internal rotation (IR) strength measures were taken in prone and sitting. Supraspinatus strength and grip strength were recorded in sitting. Shoulder ER and IR ROM were taken bilaterally. Throughout the season, the number of days missed due to rest and number of days missed due to injury were recorded. Ratios for strength measures, and ROM differences were considered to establish a correlation between time missed due to injury.
Results & Conclusion/Discussion: There were no clinically significant differences that could be derived when determining if shoulder strength and ROM in pitchers is associated with risk of injury. Out of the 21 participants, only 4 missed time due to injury. Recent data suggest that total arc of motion difference (TAMD) between throwing and non-throwing arm >5˚ indicates increased risk of injury. Of the 21 subjects, 18 subjects had a TAMD >5˚, including all 4 subjects who missed time due to injury. The range of optimal ER:IR muscle strength in the overhead athlete has been previously defined as 66%-75%. A ratio below this increases injury risk, which was seen in 7 subjects. However, by using outdated methodology when measuring ROM and strength, our data is not reliable. There were no clinically significant differences that could be derived when determining if shoulder strength and ROM in pitchers is associated with risk of injury. Out of the 21 participants, only 4 missed time due to injury. Recent data suggest that total arc of motion difference (TAMD) between throwing and non-throwing arm >5˚ indicates increased risk of injury. Of the 21 subjects, 18 subjects had a TAMD >5˚, including all 4 subjects who missed time due to injury. The range of optimal ER:IR muscle strength in the overhead athlete has been previously defined as 66%-75%. A ratio below this increases injury risk, which was seen in 7 subjects. However, by using outdated methodology when measuring ROM and strength, our data is not reliable.
Implications/Clinical Relevance: Although no conclusions were drawn from this research, the intentions behind this study can be applicable to the clinical setting. The research that this project was based on is outdated; there are more up to date studies that have established screening tools that can be used to identify risk factors for injury in overhead athletes. Strength measurements should be done bilaterally to compare the dominant side to the non-dominant side as strength numbers tend to decrease throughout a season and with injury. Strength numbers should be assessed with a handheld dynamometer as it is the gold standard for isometric strength testing. Measurements in prone are redundant; ER and IR testing should be completed in sitting only. (Abstract truncated to 500 words)
Abstract: 12
Evaluating Novel Lipid Extract-Modified Nanoliposomes for Retinoblastoma Treatment Using Y79 Cell Model and CCK-8 in-vitro Cytotoxicity Assay
Author(s): Naga Goli, Ashley Varela-Martinez, Hae Chan Kim, and Robert Campbell Faculty Advisor/Principal Investigator: Robert Campbell Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Retinoblastoma is one of the most common eye malignancies in children that develops in the retina. Repression of the disease is critical in retaining eyesight and reducing mortality. However, most chemotherapeutic agents cause unwanted side effects, often resulting from a lack of target specificity. Nanoparticles have been researched to overcome these adverse effects. Among the different nano delivery systems is cell membrane lipid-extracted nanoliposomes (CLENs). The objective of this study was to evaluate target selectivity, cytotoxicity, and related formulation and cellular properties of Y79 lipid extract (LE)-modified nanoliposomes.
Description/Methods/Materials: The suspension cell line, Y79, was selected to study the selectivity of drug-loaded CLENs in retinoblastoma. Y79 cells were seeded at 20,000 cells/mL of growth medium. Y79-CLENs included DOPC, and lipid extract (LE) derived from the Y79 cell line. Stage I of the experiment examined the cellular uptake activity of the CLENs in the Y79, varying the composition of DOPC/LE at a ratio of 90/10 or 80/20. The DPPE-rhodamine label was included in fluorescence studies. Stage II evaluated the cytotoxicity of chemotherapeutic agents loaded in Y79CLENs utilizing the CCK-8 in vitro assay. Chemotherapeutic agents used for the study were doxorubicin, gemcitabine, carboplatin, and vinblastine. Multiple myeloma cell line (RPMI 8226) and peripheral blood mononuclear cells (PBMCs) served as the non-target and off-target cellular controls, respectively.
Results & Conclusion/Discussion: The average mean diameter for DOPC nanoliposomes containing 0 and 20 mol% Y79 lipid extract content was 288 ± 3 nm and 184 ± 4 nm respectively. The average diameter varied following the incorporation of chemotherapeutic agents in CLENs. Corresponding zeta potential values: 0% (-15.5 ±1 mV) and 20% (-11.2± 0.8 mV). Particle size values for doxorubicin loaded in preparations including 0% and 20% Y79-LE content was 117 ± 5 nm and 195±8 nm, respectively. The zeta potential values for 0 and 20 mol% doxorubicin-loaded Y79-CLENs were -5.66 ± 2mV and -5.27 ± 1mV, respectively. Y79-CLENs were taken up by Y79 cells to a greater extent when compared to the DOPC control preparations. Cellular uptake summary: ratio of DOPC/LE80/20 > 90/10 > 100/0. Chemotherapeutic agents-loaded Y79-CLEN liposomes demonstrated more selective cytotoxic drug effects against Y79 cells when compared with RPMI 8226 cell line. Cellular binding and uptake of Y79-modified nanoliposomes were significantly higher for Y79 (target) cells, with diminished uptake by RPMI 8226 (non-target) and PBMCs (off-target) cell populations. This finding supports the highly selective targeting characteristics of Y79 LE-modified nanoliposomes. The average mean diameter for DOPC nanoliposomes containing 0 and 20 mol% Y79 lipid extract content was 288 ± 3 nm and 184 ± 4 nm respectively. The average diameter varied following the incorporation of chemotherapeutic agents in CLENs. Corresponding zeta potential values: 0% (-15.5 ±1 mV) and 20% (-11.2± 0.8 mV). Particle size values for doxorubicin loaded in preparations including 0% and 20% Y79-LE content was 117 ± 5 nm and 195±8 nm, respectively. The zeta potential values for 0 and 20 mol% doxorubicin-loaded Y79-CLENs were -5.66 ± 2mV and -5.27 ± 1mV, respectively. (Abstract truncated to 500 words)
Abstract: 13
Development of a Plant-based Drug Assay Using Visualization of Chemonastic Responses
Author(s): Ezra Vail, Meghan McConagle, Wilfred Asonglefac, Tyler Holmes, and Matthew Metcalf Faculty Advisor/Principal Investigator: Matthew Metcalf Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: The purpose of this project is to develop a plant-based alternative to the traditional animal model drug assay. This assay aims to use the structural similarity between NSAIDs and endogenous plant auxin hormones to visualize phytotoxicity by observing plant movements through timelapse photography. It builds on the previously observed dose-response relationship between NSAID concentration and plant growth.
Description/Methods/Materials: Here, we developed a timelapse setup to convert visual data of plant movements into a chemonastic (chemically induced plant movement) assay. Concurrently, we developed a minimally visibly intrusive rack for the plant tubes using laser-cut clear acrylic. In the current procedure, peas are grown to seedlings, placed in tubes of varying concentrations of test or control solution, photographed (one picture per minute) for a period of up to 7 days and timelapse videos assembled from the pictures. The timelapse videos show the plant response to drugs. We also developed a procedure to solubilize ibuprofen using lysine, however during control testing we observed lysine has a significant and unexpected enhancement of plant growth compared to controls.
Results & Conclusion/Discussion: We will present the timelapse videos of the results. We will present the timelapse videos of the results.
Implications/Clinical Relevance: There is an ethical imperative to limit the use of animal models in research whenever possible, and this project would offer an inexpensive replacement to the mouse anti-writhing assay.
Abstract: 15
Grape Extract Toxicity in MDCK Cells
Author(s): Anusha Chindam, Swetha Kariamkonda, Hoa, Nguyen, Alena Haynes, So Yun Jeong, and Prashant Mandela
Faculty Advisor/Principal Investigator: Prashant Mandela
Program/School: PHCOL.MS/School of Pharmacy
Purpose/Hypothesis: Ingestion of grape and grape products in Canis familiaris (dogs) causes nephrotoxicity by targeting the epithelial cells of the nephron in a concentration and timedependent manner.
Description/Methods/Materials: Cell culture and grape powder treatments: MDCK cells of female adult Canis familiaris are representative of dog distal convoluted epithelial cells. A grape powder solution of 100mg/ml was made by dissolving the grape powder in the cell culture medium containing 0.1 % DMSO. Smaller concentrations of grape powder solution were obtained through serial dilutions using culture media. Cells were incubated for 24, 48, and 72 hrs with different concentrations of grape powder solution. Cells were treated with the same concentration of sucrose to identify and compare the sugar driven osmotic effects.
Resazurin assay: Resazurin assay is performed to quantify the number of live cells and to monitor cell viability following treatment with grape powder. Following incubation with grape powder solution, cells are washed and then incubated with resazurin dye dissolved in phenol red-free EMEM medium for four hours at 37oC. Following incubation, the fluorescence was measured.
Microscopy: 96 well plates containing primary or MDCK cells are treated with different concentrations of grape powder solution at the end of the incubation time cells were examined for morphological and cytoskeletal changes.
Results & Conclusion/Discussion: Our findings suggest that MDCK cells treated with both low concentrations (1.25, 2.5, 5, and 10 mg/ml) and high concentrations ( 60, 70, 80, 90, 100 mg/ml) had a mild to moderate effect on MDCK cell viability. Following treatment with grape powder solution, cellular and morphological changes of the MDCK cells were studied using an EVOS fluorescent microscope. Increased cytoplasmic endosome formation was noticed in MDCK cells treated with higher concentrations (30 mg/ml and above) of grape powder. The endosomal appearance increases with the increased concentration of grape powder treatment. Our findings suggest that MDCK cells treated with both low concentrations (1.25, 2.5, 5, and 10 mg/ml) and high concentrations ( 60, 70, 80, 90, 100 mg/ml) had a mild to moderate effect on MDCK cell viability. Following treatment with grape powder solution, cellular and morphological changes of the MDCK cells were studied using an EVOS fluorescent microscope. Increased cytoplasmic endosome formation was noticed in MDCK cells treated with higher concentrations (30 mg/ml and above) of grape powder. The endosomal appearance increases with the increased concentration of grape powder treatment.
Implications/Clinical Relevance: Research is aimed at bettering dog health and easing the mental and economic burdens of pet owners.
Abstract: 16
Evaluation of the Penetration of Topical Retinol Products into the Skin
Author(s):
Vinh Phan and Guang Yan
Faculty Advisor/Principal Investigator: Guang Yan Program/School: PHCT.MS/School of Pharmacy
Purpose/Hypothesis: The skin is a complex and dynamic organ that serves as a barrier between the body and the external environment. The skin is composed of multiple layers, each with unique structures and functions. Photoaging, a type of skin aging caused by prolonged exposure to ultraviolet (UV) radiation, can lead to changes in the structure and function of these skin layers. Topical retinol cosmetic products are widely used for anti-wrinkle and anti-photoaging purposes. However, the quality and efficacy of these products are generally not established due to the lack of regulation from the FDA. Our preliminary data showed many products have either a much lower concentration of Retinol than claimed or different variants of retinol of which benefit hasn’t been proven. There’s also a high amount of side effects of chemical burns, irritation and sun burn. Numerous mainstream and small cosmetic companies are cashing in with their own formulation of Retinol products, advertising them as an anti-wrinkle, aging-prevention, and overall skin improving agent. Despite the widespread use of retinol-based products, multiple studies have shown their efficacy in treating photoaged skin has been limited by the instability of retinol due to its light sensitivity and tendency to oxidize.
Description/Methods/Materials: The purpose of this research is to evaluate a dozen topical retinol products with regard to their retinol content and penetration into the skin, in order to establish guidelines for selecting effective retinol products.
Twelve retinol products with varying retinol content were purchased from Amazon. The retinol content of each product was determined using HPLC. The products were applied to human cadaver skin on a heating pad for six hours. Excess product was removed with an alcohol pad, and the upper layer of the skin was removed by tape stripping 24 times before being punched out. The retinol content in the tape strips and skin was extracted with methanol and analyzed with HPLC method.
Results & Conclusion/Discussion: Two products had a retinol content in the 1% range, while two had a retinol content in the 0.3-0.5% range. Three products had a retinol content in the 0.1% range, and five products had a retinol content less than 0.05%. From the penetration study, it was found that products with higher retinol content had greater amounts of retinol in the tape strips as well as greater penetration into the skin under the stratum corneum. Retinol was undetectable in the skin for products with a retinol content of 0.1% or lower. Two products had a retinol content in the 1% range, while two had a retinol content in the 0.3-0.5% range. Three products had a retinol content in the 0.1% range, and five products had a retinol content less than 0.05%. From the penetration study, it was found that products with higher retinol content had greater amounts of retinol in the tape strips as well as greater penetration into the skin under the stratum corneum. Retinol was undetectable in the skin for products with a retinol content of 0.1% or lower.
Implications/Clinical Relevance: For selecting effective retinol products with labeled retinol content, higher retinol content will provide higher penetration into the skin and produce better result for the treatment.
Abstract: 17
Feasibility of Robot-Assisted Remote Lung Ultrasound Imaging
Author(s): Xihan Ma, Holly Schroth, Megan Gurlitz, Hannah Peloquin, Debra Crandell, Jeffrey Hill, and Haichong K Zhang
Faculty Advisor/Principal Investigator: Jeffrey Hill
Program/School: DMS/School of Diagnostic Medical Sonography
Purpose/Hypothesis: Lung ultrasound (LUS) has become standard point-of-care imaging to identify various respiratory conditions, including the early diagnosis of the novel coronavirus disease and its variants. However, performing freehand LUS requires substantial contact between the sonographer and patient, increasing the risk of disease transmission. This collaborative study aimed to assess the feasibility and safety of performing LUS with a robot arm remotely teleoperated by a sonographer to minimize patient-sonographer interaction.
Description/Methods/Materials: We utilized a previously developed robotic ultrasound system (RUSS) to perform LUS on two subjects (one male and one female). The RUSS consists of a wireless ultrasound (US) probe (C3HD, Clarius, Canada), a robot arm (Panda, Franka Emika, German) housing the probe, three patient monitoring webcams (N660, NexiGo, USA), and operator console that receives teleoperation input from a 3D mouse (SpaceMouse, 3dconnexion, USA), and displays US images and webcam views simultaneously.
The robot was mounted to a table and set at the bedside, approximately five meters from the operator console. The sonographer controlled the RUSS to sequentially land the probe on ten standard imaging targets on the frontal torso and back. The RUSS automatically applied constant contact force (3.5 N) and maintained a vertical position on the body surface for acoustic coupling. Meanwhile, the sonographer provided audio commands to guide the subject to change posture so that the robot had access to all targets.
We collected LUS images and the force applied by the robot at each target, and a Visual Analog Scale (VAS) (0-10) was used to monitor probe pressure and pain; > 4 (i.e., “hurts a little”) VAS score was used as the point of termination of the study. After the RUSS imaging session, the sonographer conducted the same imaging protocol. The lung pleural line was the primary anatomical feature for identifying the standard imaging plane. We used the image contrast-noise-ratio (CNR) of the lung pleural line to quantify its visibility.
Results & Conclusion/Discussion: 100 images (100%) were obtained and analyzed from the ten regions per subject. There were no significant differences in the averaged CNR of the RUSS and sonographer imaging (4.86 ± 2.03 vs. 5.20 ± 2.58; p=0.13), respectively. No significant differences were observed in the force applied by the robot when imaging male and female subject (3.26 ± 2.04 N vs. 3.38 ± 0.99 N; p=0.38), respectively. The VAS scores were zero throughout the imaging session, demonstrating that the RUSS does not apply exceeding pressure compared to the sonographer operator. 100 images (100%) were obtained and analyzed from the ten regions per subject. There were no significant differences in the averaged CNR of the RUSS and sonographer imaging (4.86 ± 2.03 vs. 5.20 ± 2.58; p=0.13), respectively. No significant differences were observed in the force applied by the robot when imaging male and female subject (3.26 ± 2.04 N vs. 3.38 ± 0.99 N; p=0.38), respectively. The VAS scores were zero throughout the imaging session, demonstrating that the RUSS does not apply exceeding pressure compared to the sonographer operator. (Abstract truncated to 500 words)
Author(s):
Abstract: 18
Selectivity of SK-N-DZ Lipid Extract-Modified Nanoliposomes for Targeted Delivery to Neuroblastoma
Kevin Bumanglag, Yishan Li, Thi Tran, and Robert Campbell
Faculty Advisor/Principal Investigator: Robert Campbell
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Neuroblastoma is a malignancy of the neuroendocrine system affecting pediatric patients. The disease is highly resistant to therapeutic agents, thus inspiring the need to improve clinical outcomes. Current drug agents have low specificity for neuroblastoma cells, causing unwanted side effects and contributing to poor clinical outcomes. Incorporating drugs in optimized lipid nanoparticles such as liposomes has proven to be an effective method for drug targeting. To achieve greater selectivity, lipid membrane extracts (LE) derived from neuroblastoma cells were employed in the preparation of a novel delivery system. The study aimed to optimize cell membrane lipid-extracted nanoliposomes (CLENs) for enhanced targeting of neuroblastoma compared to conventional controls.
Description/Methods/Materials: The neuroblastoma cell line, SK-N-DZ, was used for a drug selectivity study. The expansion culture of SK-N-DZ was utilized for cellular extraction purposes. The method of lipid membrane extraction was previously reported by Alharbi and Campbell, (AAPS Open 4,5(2018)). SK-N-DZ lipid extract was the main ingredient in preparing SK-N-DZ CLENs. This study prepared CLENs with various DOPC, cholesterol, DPPE-PEG5000, and SK-N-DZ lipid extract compositions. The DPPE-rhodamine label was incorporated for fluorescence and cellular uptake studies. Cell lines from different environments were used as negative controls.
Results & Conclusion/Discussion: The inclusion of SK-N-DZ LE in nanoliposomes enhanced their uptake by SK-N-DZ cells. The best-optimized composition and ratio for SK-N-DZ CLENs were DOPC/cholesterol/LE/PEG (65/10/20/5). The average particle size and value for zeta potential were 164 nm +/- 1.2 and – 7.92 +/- 1.55 mV, respectively. The inclusion of SK-N-DZ LE (2,10,20, and 40 mol%) in preparation of CLENs showed increased cellular uptake by SK-N-DZ cells compared to control (no LE included). No difference was observed in cellular uptake between 20 and 40 mol% of LE content. The subsequent inclusion of cholesterol (10, 20, 40 mol%) further increased the nanoliposome’. Additional PEG inclusion (5,10, and 20 mol%) further increased targeting. The inclusion of SK-N-DZ LE in nanoliposomes enhanced their uptake by SK-N-DZ cells. The bestoptimized composition and ratio for SK-N-DZ CLENs were DOPC/cholesterol/LE/PEG (65/10/20/5). The average particle size and value for zeta potential were 164 nm +/- 1.2 and – 7.92 +/- 1.55 mV, respectively. The inclusion of SK-N-DZ LE (2,10,20, and 40 mol%) in preparation of CLENs showed increased cellular uptake by SK-N-DZ cells compared to control (no LE included). No difference was observed in cellular uptake between 20 and 40 mol% of LE content. The subsequent inclusion of cholesterol (10, 20, 40 mol%) further increased the nanoliposome’. Additional PEG inclusion (5,10, and 20 mol%) further increased targeting.
Implications/Clinical Relevance: Current drug agents have low specificity for neuroblastoma cells causing unwanted side effects and contributing to poor clinical outcomes. The use of modified nanoliposomes using lipid extract of targeted cancer cells for the treatment will improve drug uptake and reduce side effects.
Abstract: 19
Investigating the Effects of Manual Therapy on Pain Processing and Modulation: A Scoping Review
Author(s): Mason Gray, Grace Naylor, Jacob Halpern, and Christopher Joyce Faculty Advisor/Principal Investigator: Christopher Joyce
Program/School: PTH.DPT/School of Physical Therapy
Purpose/Hypothesis: Dysfunction in nociceptive transmission and modulation is associated with worse prognosis, pain, disability, in patients with musculoskeletal conditions. Manual therapy (MT) can favorably affect these neurophysiological processes and improve pain. Quantitative sensory tests (QST) are often used in research to indirectly measure nociceptive processing. Currently, there is an abundance of MT techniques and similarly numerous forms of QST. Additionally, clinical populations, study designs, and measurement timepoints, are not well-identified. The purpose of this scoping review was to map the current evidence examining MT’s effect on QST measures.
Description/Methods/Materials: The Arskey and O’Malley framework guided this review. In collaboration with a health sciences librarian, a systematic search of Medline and CINAHL through March 2022 was performed. All records were imported into a Cochrane-based online reference manager. Studies were included if they were clinical trials on patients with musculoskeletal pain, had at least two QST measurement timepoints, and utilized a MT intervention related to physical therapy. Studies were excluded if they involved asymptomatic participants or patients with neuropathic, visceral, or cancer-related pain. Two authors independently screened all titles and abstracts. All four authors were involved in full-text review, data extraction, and disagreement resolution.
Results & Conclusion/Discussion: 1,463 studies were screened. Data were extracted on 235 studies. The most common MT techniques were joint mobilization (32.7%), joint manipulation (28.1%), soft tissue mobilization (27.6%), and needling-based techniques (23.4%). Pain pressure threshold (PPT) was the predominant QST (88.1%), followed by thermal sensitivity (4.0%) and temporal summation (2.7%). Twenty-five different musculoskeletal conditions were investigated, most common were neck pain (26.8%), back pain (15.0%), osteoarthritis (8.7%), and temporomandibular disorders (7.9%). Nearly all (86.7%) of the studies were less than 4 weeks long and 29.0% were only one session. The majority of QST measurements were taken immediately after the intervention (87.6%) and/or within one month of the trial’s end (44.6%). 1,463 studies were screened. Data were extracted on 235 studies. The most common MT techniques were joint mobilization (32.7%), joint manipulation (28.1%), soft tissue mobilization (27.6%), and needling-based techniques (23.4%). Pain pressure threshold (PPT) was the predominant QST (88.1%), followed by thermal sensitivity (4.0%) and temporal summation (2.7%). Twenty-five different musculoskeletal conditions were investigated, most common were neck pain (26.8%), back pain (15.0%), osteoarthritis (8.7%), and temporomandibular disorders (7.9%). Nearly all (86.7%) of the studies were less than 4 weeks long and 29.0% were only one session. The majority of QST measurements were taken immediately after the intervention (87.6%) and/or within one month of the trial’s end (44.6%).
Implications/Clinical Relevance: Understanding the mechanisms behind MT may lead to more targeted application. QST may be used clinically to determine who would benefit from which MT approach while objectively measuring changes in pain processing. However, feasibility of QST measures other than PPT may be a barrier to research and practice.
Abstract: 20
Effectiveness of Pharmaceutical Care Curriculum on Improving Students Abilities to Communicate with the Deaf/Hard of Hearing Population to Increase Patient Outcomes
Author(s): Amelia Olson, and Carrie Graham Faculty Advisor/Principal Investigator: Carrie Graham
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: In the United States of America, it is reported that deaf patients tend to experience fear, mistrust, and frustration in health care encounters more than patients who are not deaf. 1 A study was conducted that showed that miscommunication happens most frequently between a patient and their healthcare provider which can lead to further miscommunication in general. 1 This study also showed that deaf and hard of hearing patients had the most difficulties with communication and lacked a full understanding of their diagnosis and treatment plans. 1 When research was done about people with disabilities in acute care, it was found that the presence of a deaf communication problem was significantly related to an increase in the risk of deaf patients experiencing a preventable medication related event. 1 In fact, deaf people who can read lips can really only understand about 30-40% of their medical interactions.
Description/Methods/Materials: Google scholar was the resource used as my search engine. The key terms were “deaf”, “patient outcomes”, “communication”, “pharmacy”, “teaching”. Key terms were combined by the term "AND". Exclusions to this search was a ten year limit since the research was published. Furthermore, I used the resource sections of the research articles I read to find more articles about this topic.
Results & Conclusion/Discussion: When research was done about people with disabilities in acute care, it was found that the presence of a deaf communication problem was significantly related to an increase in the risk of deaf patients experiencing a preventable medication related event. 1 In fact, deaf people who can read lips can really only understand about 30-40% of their medical interactions. 1 A study was conducted that compared deaf patients medication comprehension to hard of hearing patients medical comprehension. They found that even after both groups were educated the same way on their medications, deaf patients had significantly lower comprehension scores about their medications than the hard of hearing patients. 2 Through this it was discovered that adjusting the medication information provided by pharmacists according to the individual needs, could help improve deaf patients’ knowledge of their medications. 2 Thus resulting in greater patient adherence and outcomes of the deaf population. 2 When research was done about people with disabilities in acute care, it was found that the presence of a deaf communication problem was significantly related to an increase in the risk of deaf patients experiencing a preventable medication related event. 1 In fact, deaf people who can read lips can really only understand about 30-40% of their medical interactions. 1 A study was conducted that compared deaf patients medication comprehension to hard of hearing patients medical comprehension. They found that even after both groups were educated the same way on their medications, deaf patients had significantly lower comprehension scores about their medications than the hard of hearing patients. 2 Through this it was discovered that adjusting the medication information provided by pharmacists according to the individual needs, could help improve deaf patients’ knowledge of their medications. 2 Thus resulting in greater patient adherence and outcomes of the deaf population. (Abstract truncated to 500 words)
Abstract: 21
Improving Chagas Disease Treatment using a Pyridinyl Pyrazole Scaffold
Author(s): Margi Shingala, Lee Hyejin, and Carolyn Friel Faculty Advisor/Principal Investigator: Carolyn Friel
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: The purpose of the research is to develop orally bioavailable drugs for the treatment of Chagas disease. The parasite Trypanosoma cruzi, which only exists in the Americas, is what causes Chagas disease. It spreads to both people and animals by insect vectors. It's also called as American trypanosomiasis or Chagas disease (T. cruzi infection). There may be swelling at the infection site, fever, tiredness, body aches, rash, and nausea as symptoms, if treated untreated can lead to lifelong infection. The compounds synthesized have been optimizing based on the structural activity-relationships (SAR) of R1 and R2 group substituents. Four compounds that take advantage of both the R1 and R2 chemical space are planned. The impacts of the substituent changes in these locations will add to our knowledge of compound activity versus Chagas disease.
Description/Methods/Materials: The starting pyridinyl pyrazole was provided by the Drugs for Neglected Diseases institute (DNDi). The R1 group was added via a reductive amination reaction. The reductive amination was conducted using nonaromatic ketones in dichloroethane using molecular sieves, glacial acetic acid as a proton source and sodium triacetoxyborohydride as a reducing agent. Reactions were followed by thin layer chromatography for completion and purified using HPLC after work-up. Compound structures were determined using proton and carbon NMRs. R2 group substitution (Cl) was conducted using N-chlorosuccinimide at 0ºC and worked up using literature procedures. Reaction yields were excellent for both modifications (80-90%).
Results & Conclusion/Discussion: The synthesis of two novel compounds N-cyclohexyl-4cyclopropyl-3-(pyridin-2-yl)-1H-pyrazol-5-amine and N-cyclopentyl-4-cycopropyl-3-(pyridin-2-yl)-1Hpyrazol-5-amine are complete and both compounds were confirmed using carbon and proton NMR. The 4-chloro starting material has been synthesized and will be used to prepare the 4-chloro derivatives of the first two compounds. All compounds will be tested for biological activity by the DNDi at the conclusion of the semester. The synthesis of two novel compounds N-cyclohexyl-4cyclopropyl-3-(pyridin-2-yl)-1H-pyrazol-5-amine and N-cyclopentyl-4-cycopropyl-3-(pyridin-2-yl)-1Hpyrazol-5-amine are complete and both compounds were confirmed using carbon and proton NMR. The 4-chloro starting material has been synthesized and will be used to prepare the 4-chloro derivatives of the first two compounds. All compounds will be tested for biological activity by the DNDi at the conclusion of the semester.
Implications/Clinical Relevance: The goal of the project is to develop new drugs to treat Chagas disease. Currently, only two drugs, benznidazole and nifurtimox are approved. They are effective only when administered soon after an infection. So, it is required to develop new drugs to cover the chronic stage of the disease. Despite the efficacy for the acute stage, there are side effects such as heart problems. So, it is another reason we need to develop new drugs to reduce side effects. Despite the need to develop a new drug for Chagas disease, pharmaceutical companies do not invest resources due to lack of economic benefit and difficulties in studying the cycle of T.cruzi, the vector of Chagas disease.
Abstract: 22
Gamification of Learning for the Purposes of Pharmacy Education: Piloting a Pharmaceutical Industry Role-Playing Game
Author(s): Myra Fu, David Farber, Stephanie Wu, BeiBei Ding, Allen Amedume, Rebecca Zhou, Leah Valdes, Alicia Kim, Joshua Liu, Shani Patel, Renee Nguyen, Jacob Kirkpatrick, and Loriel J. Solodokin
Faculty Advisor/Principal Investigator: Loriel J. Solodokin
Program/School: N/A - Sanofi Fellowship Program
Purpose/Hypothesis: The objective of this study was to understand the effectiveness of gamified learning among pharmacy students, in terms of assessing their pre-/post knowledge of the pharmaceutical industry and interest in pursuing a fellowship.
Description/Methods/Materials: We created a role-playing game, in which students were presented with a drug development scenario. Students were divided into groups of 10-12 and each group was facilitated by either a PharmD fellow or our academia mentor (PharmD). Student groups would earn points (scaled based on the most appropriate responses that could be made: 3 points for best answer, 2 for next best, 1 for third best, and/or 0 for worst choice) and the group with the highest number of points (i.e., the group closest to bringing the drug to market) would win. Following the interactive drug development activity, students were requested to complete a Qualtrics survey, which assessed their pre- and post-perceptions of the gamified learning activity. We used descriptive statistics to analyze the results of the survey.
Results & Conclusion/Discussion: Post-survey, 93% of students agreed that gamification was effective in learning new material, 84% agreed that gamification was effective in applying existing knowledge, and 85% agreed that that gamification should be used more often in the curriculum. Post-survey, 93% of students agreed that gamification was effective in learning new material, 84% agreed that gamification was effective in applying existing knowledge, and 85% agreed that that gamification should be used more often in the curriculum.
Implications/Clinical Relevance: This study suggests that our gamified learning exercise may be effective in engaging pharmacy students and introducing them to learning about the pharmaceutical industry. Larger, comparative studies will be needed to further assess the impact of gamified learning on factual material comprehension, knowledge retention, and student engagement, compared to didactic lesson formats.
Abstract: 23
Expressions of Platelet, Drug Metabolism, and Vitamin D Receptor
Pathway Genes are Dysregulated between Early Stage and Advanced Stage Breast Cancer in Younger Patients
Author(s): Bahareh Parcheh Bafi and George Acquaah-Mensah Faculty Advisor/Principal Investigator: George Acquaah-Mensah Program/School: PHCOL.PHD/School of Pharmacy
Purpose/Hypothesis: The Incidence rate of breast cancer among very young adults is becoming an object of public concern in South Korea and elsewhere. There are a variety of presentations of breast cancer, with varying degrees of severity, and varying molecular presentations. These studies were designed to gain some insights into the molecular pathways that play a major role in the transition from early- to advanced-stage cancer in young patients.
Description/Methods/Materials: RNAseq data generated from a South Korean study of 50 participants aged under 35 years at diagnosis was leveraged. We specified two groups based on their tumor stage at diagnosis including donors with early-stage tumors (no stage or stage 1 tumor) and donors with more advanced-stage tumors (stage 2 or 3) and compared them.
First, we did Differential expression analysis (DESeq) to see if any of these genes are significantly differentially expressed between these two groups (DEGs). The 407 DEGs identified were subjected to Enrichment analysis (EnrichR) to discover the biological pathways associated with these gene. Reactome and BIOCarta pathway database were used in this analysis. In the next step by the help of Molecular Signatures Database (MSigDB) with Gene set enrichment analysis (GSEA) we identified pathways enriched in ranked Human BIOCarta VDR pathway gene lists.
Results & Conclusion/Discussion: There were three BIOCarta database pathways over-represented (p<0.03) among the DEGs, spanning six 6 genes in total. The three are: i) Platelet pathways with F2 and F11, which are critical for making prothrombin (coagulation factor II) and factor XI. ii) Gammaaminobutyric Acid Receptor Life Cycle pathway which includes GABRA03 (GABA receptor subunit α3) and UBA1 (Ubiquitin-like modifier activating enzyme 1). iii) Fibrinolysis Pathway, which also includes the DEGs UBA1 and F2. In similar enrichment analysis using the Reactome database, two pathways over-represented among the DEGs were identified. They are i) Drug ADME pathway (p < 0.02), which includes seven DEGs , of which three are involved in glucuronidation pathway (UGT1A9, UGT1A8, UGT1A7). ii) Phase II - Conjugation of Compounds pathway (p<0.05) including 6 genes, three of which are the same as the glucuronidation pathway genes in the Drug ADME pathway. GSEA analysis showed that Vitamin D receptor pathway genes are enriched in early-stage tumors. Most of these genes are involved in chromatin remodeling. There were three BIOCarta database pathways over-represented (p<0.03) among the DEGs, spanning six 6 genes in total. The three are: i) Platelet pathways with F2 and F11, which are critical for making prothrombin (coagulation factor II) and factor XI. ii) Gamma-aminobutyric Acid Receptor Life Cycle pathway which includes GABRA03 (GABA receptor subunit α-3) and UBA1 (Ubiquitin-like modifier activating enzyme 1). iii) Fibrinolysis Pathway, which also includes the DEGs UBA1 and F2. In similar enrichment analysis using the Reactome database, two pathways over-represented among the DEGs were identified. They are i) Drug ADME pathway (p < 0.02), which includes seven DEGs , of which three are involved in glucuronidation pathway (UGT1A9, UGT1A8, UGT1A7). ii) Phase II - Conjugation of Compounds pathway (p<0.05) including 6 genes, three of which are the same as the glucuronidation pathway genes in the Drug ADME pathway. (Abstract truncated to 500 words)
Author(s):
Abstract: 24
Synthesis of New Antimalarial Drugs in the Age of Resistance
Harpreet Kaur and Carolyn Friel
Faculty Advisor/Principal Investigator: Carolyn Friel
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Malaria is a life-threatening disease caused by microscopic parasites called Plasmodium, which are transmitted to human beings by mosquitoes. The Malaria Libre (ML) program provides researchers the ability to openly collaborate to identify, synthesize, and test novel compounds to identify preclinical candidates for the treatment of malaria. The Medicines for Malaria Venture (MMV) hosts the data repository and offers drug discovery and parasitology advise through monthly Zoom meetings. One of the ML goals is to develop drugs for treatment resistant malaria. Treatment failure is due to the complex life cycle of Plasmodium and the emergence of drugs resistant strains of Plasmodium falciparum. The goal of this project was to synthesize 5 novel compounds for biological testing by ML.
Description/Methods/Materials: This project involves the chemical synthesis of 5 new antimalarial compounds. Starting material, an aminopyridinol, was provided by ML. Discussions with the ML team helped guide the selection of compounds to synthesize. Reductive amination was used to produce compounds with fluorine at the o, m, and p-substitution of the phenyl to explore the chemical space to improve anti-plasmodial activity. A compound with steric bulk was synthesized based on the metabolic liability of previously tested compounds. The chemical reaction was followed by thin layer chromatography. After reaction completion it was worked-up and concentrated for purification via Biotage chromatography. Structures were confirmed with both carbon and proton NMR.
Results & Conclusion/Discussion: The successful chemical synthesis of 4 of 5 novel compounds will be reported. Percent yields ranged 22% to 50%. Proton and carbon NMRs were obtained. After all, 5 compounds are synthesized they will be sent to BU for elemental analysis and the MMV for biological assays.
The successful chemical synthesis of 4 of 5 novel compounds will be reported. Percent yields ranged 22% to 50%. Proton and carbon NMRs were obtained. After all, 5 compounds are synthesized they will be sent to BU for elemental analysis and the MMV for biological assays.
Implications/Clinical Relevance: Open-source antimalarial drug development increases the number and diversity of new molecules evaluated in pre-clinical models. Antimalarial drug therapy resistance is a grown problem and new treatment options are needed. Compounds synthesized during this project provide additional data points for open-source research MMV collaborations.
Abstract: 25
Visual Comparison of Chemonastic Responses in Two Plant Species Across Different Time Scales. Development of a Plant-Based Alternative to Animal Drug Testing
Author(s): Songuun Liu, Nasr Issa, Wilfred Asonglefac, Meghan McGonagle, and Matthew Metcalf Faculty Advisor/Principal Investigator: Matthew Metcalf Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Animal-based drug assays are the gold standard for new drug preclinical trials, but animal-based drug tests also have ethical questions and limitations. The development of plantbased drug assays can alleviate these ethical issues. This project focuses on the observation of different plants’ chemonastic movements in response to drugs, and further appraising the feasibility of plant-based drug assay. The purpose of this project is to develop a potential drug test which eliminates animals and demonstrates cross species (and family) viability. We hypothesize that the MA native morphological analog plant will exhibit similar chemonastic leaf folding in response to chemicals as Mimosa pudica.
Description/Methods/Materials: We examine the effects of various drugs on the chemonastic response in two different types of plants using video and timelapse capture. To develop the assay we selected Mimosa pudica (MP) which folds its leaves shut in response to touch using a chemical message, which will will serve as the known control. The experimental system is a morphological analog of MP native to Massachusetts (MA). The assay will examine the ability of drugs to trigger the chemonastic response in each plant to determine if the drug effect is viable across species similar to comparison of rats to mice or rats to humans. To conduct the experiments MA seeds were harvested in the fall and vernalized until January and MP seeds were obtained. Both MP and MA seeds were planted (Jan, 2023) and grown to the seedling stage and tested for folding response.
Results & Conclusion/Discussion: MP seedlings were found to fold in response to touch, however the MA seedlings were found insensitive to touch (not expected). During March all seedlings except two Mimosa pudica seedlings died. New seeds were started March 15. We will show video of the response to touch at the event and anticipate live demonstrations. MP seedlings were found to fold in response to touch, however the MA seedlings were found insensitive to touch (not expected). During March all seedlings except two Mimosa pudica seedlings died. New seeds were started March 15. We will show video of the response to touch at the event and anticipate live demonstrations.
Implications/Clinical Relevance: We believe that these plants have the ability to produce a viable model system for drug testing which can eliminate an animal drug testing model and improve the ethical standards for drug testing
Abstract: 26
The Quality of Life and Gene Expression Profiles of Pancreatic Cancer Patients: ExCigarette Smokers against Never Smokers
Author(s): Akpene Tetteh and George Acquaah-Mensah Faculty Advisor/Principal Investigator: George Acquaah-Mensah Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: Our hypothesis is that pancreatic cancer patients who are ex-cigarette smokers have decreased quality of life compared with those who have never smoked a cigarette.
Description/Methods/Materials: Patient gene expression (RNAseq) data was sourced from the Pancreatic Cancer and Action Network (PanCAN). Kaplan Meier survival plots were used to characterize the quality of differences between current smokers, ex-smokers, and never-smokers. The Eastern Cooperative Oncology Group (ECOG) performance status scale was used to compare the quality of life and the patient's ability to perform daily activities. A tidyverse Bioconductor package in R was used for data structuring, whereas a DESeq2 Bioconductor package in R was used to identify and analyze genes differentially expressed between the cohorts. Modules of the STRING human protein-protein interaction network that showed regions with a high incidence of significant DEGs over subsets of conditions were identified using jActive Modules, an application within the graph visualizer tool, Cytoscape. Cluster method, ward.D with Euclidean distance was used to group the patients. The Reactome database was used to analyze the biological pathway overrepresentation among genes in each cluster.
Results & Conclusion/Discussion: We found the quality of life of the patients to be significantly different based on their smoking history (never-smokers (n=52), ex-smokers (n=21), and current smokers (n=4), p < 0.00027). Ex-smokers had the worst quality of life and chances of survival compared to never and current-smokers. In addition, a pair-wise comparison was made between current-smoker against the ex-smoker, never-smokers against ex-smoker, and current-smoker against never-smokers. There were significant differences between each group, with p-values of 0.0018, 0.0017, and 0.018, respectively. PRSS1, NANOG, DKK1, MATK, CXCL12, XCL2, PLG, VMO1, C4A, CPA6, C8orf34, and CELA3A genes had increased expression among the never-smokers compared with ex-smokers. Whiles AMY2A, PNLIP, and CETP genes had decreased expression in the never smokers compared with ex-smokers. AMY2A, C4A, CXCL12, DKK1, MATK, NANOG, PLG, PNLIP, PRSS1, and XCL2 genes were found in sixteen Reactome entities. We found CELA3A and VMO1 not to be associated with any Reactome entity. Gene Set Enrichment Analysis (GSEA) was conducted to determine whether an a priori-defined set of genes shows statistical significance. We found the quality of life of the patients to be significantly different based on their smoking history (neversmokers (n=52), ex-smokers (n=21), and current smokers (n=4), p < 0.00027). Ex-smokers had the worst quality of life and chances of survival compared to never and current-smokers. In addition, a pair-wise comparison was made between current-smoker against the ex-smoker, never-smokers against ex-smoker, and current-smoker against never-smokers. There were significant differences between each group, with p-values of 0.0018, 0.0017, and 0.018, respectively. PRSS1, NANOG, DKK1, MATK, CXCL12, XCL2, PLG, VMO1, C4A, CPA6, C8orf34, and CELA3A genes had increased expression among the never-smokers compared with ex-smokers. Whiles AMY2A, PNLIP, and CETP genes had decreased expression in the never smokers compared with ex-smokers. AMY2A, C4A, CXCL12, DKK1, MATK, NANOG, PLG, PNLIP, PRSS1, and XCL2 genes were found in sixteen Reactome entities. We found CELA3A and VMO1 not to be associated with any Reactome entity. Gene Set Enrichment Analysis (GSEA) was conducted to determine whether an a priori-defined set of genes shows statistical significance. (Abstract truncated to 500 words)
Abstract: 27
The Evaluation of Diuretic Patterns in Hospitalized Heart Failure Patients in a Rural Academic Medical Center in Northern New England
Author(s):
Susan D'Anna, Margaret Emmons, Yong Zhao, and Nancy Street
Faculty Advisor/Principal Investigator: Nancy Street
Program/School: NURS.DNP/School of Nursing
Purpose/Hypothesis: Heart failure (HF) is a chronic condition leading to human suffering, correlating with increased morbidity and mortality. By 2030 HF will affect more than 8 million people in the United States (US) with an estimated cost of $69.8 billion annually. HF is the leading cause of hospitalization and hospital readmission worldwide. The primary reason for hospitalization is congestion, or volume overload, leading to of shortness of breath and decreased quality of life. Intravenous (IV) diuretic administration is the cornerstone of management for the HF patient. Until recently there have been no guidelines directing its use. Inadequate inpatient (IP) IV diuretic management results in prolonged symptoms of congestion and hospital length of stay (LOS). Literature review reveals no clear consensus about best diuretic approach. Despite this, a recently published review provides evidence guiding best diuretic practice in the hospitalized HF patient. This retrospective improvement project aimed to 1) examine if recent diuretic treatment guidelines regarding diuretic dosing on hospital day 1 (HD 1) impacted LOS of patients hospitalized with HF on an IP advanced practice provider (APP) service in a rural academic medical center over six months and 2) examine if the effect of intensity diuretic dosing on HD 1 impacted change in renal function and weight over LOS in this same population.
Description/Methods/Materials: Charts of HF patients admitted to the IP APP service from 01/01/2021 thru 06/30/2021 were reviewed. The intensity of diuretic dosing on HD 1 compared to total home daily diuretic (TDD home) dosing was calculated for 70 patients. Diuretic doses were translated into oral furosemide equivalents (40 mg furosemide = 20 mg IV furosemide = 20 mg torsemide = 1 mg bumetanide). Patients were divided into 2 groups based on ratio of TDD on HD 1/ TDD home prior to admission (< 2 X intensity of TDD home and ≥2 X TDD home). Data analysis was performed comparing the 2 groups for LOS, change in serum creatinine (sCr) ratio (discharge sCr/admission sCr) and change in weight ratio (discharge weight/ admission weight) over LOS
Results & Conclusion/Discussion: The group receiving ≥2 X the intensity TDD home on HD 1 had a mean LOS that was almost 1 day less than the group receiving less intense diuretic dosing on HD1 (M=4.47, SD= 2.48 vs M=5.42, SD= 2.93, P=0.22). The ≥2 group had a higher percentage of patients with net change sCr ratio < 1.25 vs. ≥ 1.25 (80.4% vs 73.7%, P= 0.779). Both groups correlated to a change in weight ratio of > 0.9 (84.2% for the < 2 group vs. 90.2% for the ≥2 group, P= 0.781). The group receiving ≥2 X the intensity TDD home on HD 1 had a mean LOS that was almost 1 day less than the group receiving less intense diuretic dosing on HD1 (M=4.47, SD= 2.48 vs M=5.42, SD= 2.93, P=0.22). The ≥2 group had a higher percentage of patients with net change sCr ratio < 1.25 vs. ≥ 1.25 (80.4% vs 73.7%, P= 0.779). Both groups correlated to a change in weight ratio of > 0.9 (84.2% for the < 2 group vs. 90.2% for the ≥2 group, P= 0.781).
Implications/Clinical Relevance: This quality improvement project, examining diuretic dosing in a small population of HF patients in a single institution suggests opportunities for practice improvement, resulting in improved patient and fiscal outcomes.
Abstract: 28
Optimization and Evaluation G401-CLENs for Enhanced Targeting of Rhabdoid Tumors
Author(s): Varun Kudchadker, Yeji Seo, Ellie Solitro, and Robert Campbell
Faculty Advisor/Principal Investigator: Robert Campbell
Program/School: PharmD.DPH/ School of Pharmacy
Purpose/Hypothesis: One approach to improve drug delivery to cancer cells is through the use of nanoliposomes to transport drugs to their targets. This study aimed to develop G401-CLENs, a delivery system that utilizes cellular membrane lipid extracts derived from rhabdoid tumor cells and conventional lipid components to improve selective targeting of the target cell population.
Description/Methods/Materials: In-vitro culture and expansion of rhabdoid tumor cell line G401 cells were performed in order to obtain cells. The development of G401-CLENs involves the inclusion of the lipid extract (LE) of the G401 cell membrane. The standard lipid components DOPC, DOTAP, and DPPE-PEG5000 are also available. We solely used DPPE-rhodamine lipids for fluorescence experiments. To assess the effectiveness of formulations, doxorubicin, and vinblastine, two chemotherapy drugs, were used in cell viability and cytotoxicity experiments. Studies on cellular absorption and physicochemical characterization of CLEN preparations with 0 to 20 mol% G401 LE content were part of phase I of the evaluation process. Hoechst33342/propidium iodide cell viability and cytotoxicity assays were used in phase II of the evaluation along with different concentrations of doxorubicin and vinblastine-loaded CLENs applied to the G401 cells.
Results & Conclusion/Discussion: The optimal composition for G401-CLENs was DOPC/DPPEPEG5000/LE (93/2/5). The average size and zeta potential were 198 ± 16 nm (n=5) and –12 ± 1.2 mV (n=5), respectively. The optimized G401-CLENs showed increased uptake by G401 cells compared to SK-N-DZ control cells in cell selectivity studies. The inclusion of DOTAP generally increased overall cellular uptake but decreased selective uptake of G401-CLENs. The results support significant cellular uptake of preparations consisting of 5 mol% LE compared to those with 0, 10, and 20 mol% G401 LE content. In a dose-dependent manner, Doxorubicin loaded in G401-CLENs reduced rhabdoid tumor cell viability compared to doxorubicin loaded in conventional liposome preparations. The optimal composition for G401-CLENs was DOPC/DPPE-PEG5000/LE (93/2/5). The average size and zeta potential were 198 ± 16 nm (n=5) and –12 ± 1.2 mV (n=5), respectively. The optimized G401-CLENs showed increased uptake by G401 cells compared to SK-N-DZ control cells in cell selectivity studies. The inclusion of DOTAP generally increased overall cellular uptake but decreased selective uptake of G401-CLENs. The results support significant cellular uptake of preparations consisting of 5 mol% LE compared to those with 0, 10, and 20 mol% G401 LE content. In a dose-dependent manner, Doxorubicin loaded in G401-CLENs reduced rhabdoid tumor cell viability compared to doxorubicin loaded in conventional liposome preparations.
Implications/Clinical Relevance: Rhabdoid tumor is a rare and highly aggressive form of cancer that can arise in various soft tissues throughout the body, such as the kidney, liver, and peripheral nerves. Most commonly diagnosed in infants and young children, although they can occur at any age. Rhabdoid tumors are particularly challenging to treat due to their aggressive nature and tendency to spread to other parts of the body. Despite advances in treatment options, the overall survival rate for patients with rhabdoid tumors remains relatively low. Therefore, research efforts are focused on developing new and more effective therapies.
Abstract: 29
Piperlongumine Reverses EGFR Resistance as an Adjuvant Treatment in Lung Cancer Cells
Author(s): Shail Modi, Terrick Andey, and George Acquaah-Mensah Faculty Advisor/Principal Investigator: Terrick Andey
Program/School: PHCOL.PHD/School of Pharmacy
Purpose/Hypothesis: Piperlongumine will induce a potent anticancer response in non-small cell lung carcinoma cells (NSCLC) and overcome resistance.
Description/Methods/Materials: Anticancer efficacy of piperlongumine (PPL), erlotinib (ERL), and gefitinib (GEF) were investigated using a resazurin-dye assay in H1299 (EGFR wild-type) and H1975 (EGFR-T790M-mutation) cell lines, with cisplatin (CIS) as a positive control. Treatment of cells with PPL, ERL, GEF, and CIS along, and in combination was performed at various concentrations, and cell viability was determined after 72 h. The potency (IC50) of the treatment was computed using linear regression analysis. To determine the mechanism of Piperlongumine-induced toxicity, we performed a cellular reactive oxygen assay using DCFDA/H2DCFDA Cellular ROS Assay Kit (Abcam, USA). Apoptosis induction was determined by fluorescence microscopy using acridine orange/ethidium bromide (AO/EB) staining, and by flow cytometry using Muse™ Annexin V and Dead Cell Staining Kit (Luminex, USA). The effect of treatment on EGFR-mediated oncogenic signaling was studied by immunoblotting for markers of MAPK (EGFR mutant (L858R), p-EGFR, Akt, p38 MAPK, p44/p42 MAPK) and apoptotic signaling (Bcl-2, Cleaved caspase 3, Cleaved caspase 7, p53).
Results & Conclusion/Discussion: PPL exhibited a potent cytotoxic effect in H1299 (5.84 ± 0.04 µM) and H1975 (6.05 ± 0.31 µM) cells compared to ERL (138.83 ± 9.62 µM, 51.92 ± 2.34 µM), GEF (219.43 ± 22.69 µM, 47.22 ± 3.97 µM), and CIS (57.64 ± 3.06 µM, 100 ± 3.06 µM) respectively. The combination treatment of PPL with GEF and ERL showed a significant reduction in cancer cells compared to control in both cell lines. ROS induction was observed with the combination treatment; however, there was no significant difference in the ROS levels compared to the control. AO/EB staining indicated cell death via apoptosis. The combination of PPL and GEF had a significant increase in apoptotic cell death in the mutant cell line as compared to the control which was confirmed with flow cytometry analysis. Treatment with PPL alone and in combination induced antimitogenic and apoptotic responses at the molecular level. PPL exhibited a potent cytotoxic effect in H1299 (5.84 ± 0.04 µM) and H1975 (6.05 ± 0.31 µM) cells compared to ERL (138.83 ± 9.62 µM, 51.92 ± 2.34 µM), GEF (219.43 ± 22.69 µM, 47.22 ± 3.97 µM), and CIS (57.64 ± 3.06 µM, 100 ± 3.06 µM) respectively. The combination treatment of PPL with GEF and ERL showed a significant reduction in cancer cells compared to control in both cell lines. ROS induction was observed with the combination treatment; however, there was no significant difference in the ROS levels compared to the control. AO/EB staining indicated cell death via apoptosis. The combination of PPL and GEF had a significant increase in apoptotic cell death in the mutant cell line as compared to the control which was confirmed with flow cytometry analysis. Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level.
Implications/Clinical Relevance: Piperlongumine can be used as an adjuvant therapy with EGFR-TKIs to induce a potent anticancer response against NSCLC as well as helps with overcoming resistance caused by cancer cells to the EGFR-TKI therapies.
Author(s):
Abstract: 30
Polycystic Ovarian Syndrome (PCOS) and Conception
Alison Wolfe and Donna Fife
Faculty Advisor/Principal Investigator: Donna Fife
Program/School: NURS.FNP.MSN/School of Nursing
Purpose/Hypothesis: PICO(T) Question: In females with polycystic ovarian syndrome (PCOS) (P), what is the effect of non-pharmacological interventions (I) in comparison to pharmacological interventions (C) on fertility/ability to conceive (O) during their reproductive years (T)?
Description/Methods/Materials: PCOS is:
• An increasingly prevalent, complex medical condition affecting approximately 7 to 15 percent of reproductive-age women (ages 12 to 51 approximately)
• A heterogeneous disorder characterized by:
o Menstrual irregularities, hyperandrogenism, and polycystic ovaries
o Symptoms can vary significantly
Those with PCOS are at an increased risk for:
• Infertility, obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, dyslipidemia, mental health conditions (anxiety, depression), and endometrial cancer
PCOS and Infertility
• Roughly 75 percent are anovulatory and will struggle with infertility
• Leading cause of anovulatory infertility
Exploration of numerous studies has revealed a wide selection of non-pharmacological and pharmacological interventions whose primary intent is to induce ovulation to increase conception.
Results & Conclusion/Discussion: Non-Pharmacologic Interventions
Lifestyle
• First-line treatment
• Diet: Low glycemic diet to improve insulin resistance
• Exercise: Aerobic exercises to improve quality of life and fertility
• Stress management: Reduce anxiety/depression
Acupuncture
• Not recognized as an infertility treatment
• May help reduce stress and promote weight loss
• Insulin desensitizer: Improves fasting glucose levels and lower serum insulin
Pharmacologic Interventions
Clomiphene & Letrozole
• Comparable levels of efficiency when it comes to ovulation induction
• Frequency of pregnancy was slightly lower with clomiphene than letrozole
• Decision on which to prescribe based on the patient’s tolerance, cost, and side effects
• Clomiphene (Clomid)
o First-line treatment for ovulation induction
o High rate of ovulation yet lower rate of pregnancy
o Increases estrogen levels
• Letrozole
o Increasing in popularity due to less monitoring due to fewer complications and side effects
o Decreases estrogen levels
Addition of Dexamethasone
• Increases the ovarian response to ovulation-inducing medications (like letrozole)
• Dexamethasone and letrozole together = a significantly higher rate of pregnancy
Metformin
• Prescribed for:
o Improving metabolic status and reproductive dysfunction
o Reduces body weight, lowers blood pressure and serum insulin
o High incidence of gastrointestinal adverse effects
• Lower serum insulin levels improvements in menstrual cycle regulation, and increased chances of ovulation higher chance of conception
Supplementation
• No supplementation regimens recognized as effective in managing PCOS
• Examined supplements included:
o Calcarea Carbonica, Lycopodium Clavatum, Natrum Muriaticum, Pulsatilla, Nux Vomica, Sepia, and Staphysagria
o Myo-inositol
Hormonal homeostasis by reducing testosterone and serum insulin improved insulin resistance and increased ovulation rates Non-Pharmacologic Interventions
Lifestyle
• First-line treatment
• Diet: Low glycemic diet to improve insulin resistance
• Exercise: Aerobic exercises to improve quality of life and fertility
• Stress management: Reduce anxiety/depression
Acupuncture
• Not recognized as an infertility treatment
• May help reduce stress and promote weight loss
• Insulin desensitizer: Improves fasting glucose levels and lower serum insulin
Pharmacologic Interventions
Clomiphene & Letrozole
• Comparable levels of efficiency when it comes to ovulation induction
• Frequency of pregnancy was slightly lower with clomiphene than letrozole
• Decision on which to prescribe based on the patient’s tolerance, cost, and side effects
• Clomiphene (Clomid)
o First-line treatment for ovulation induction
o High rate of ovulation yet lower rate of pregnancy
o Increases estrogen levels
• Letrozole
o Increasing in popularity due to less monitoring due to fewer complications and side effects
o Decreases estrogen levels
Addition of Dexamethasone
• Increases the ovarian response to ovulation-inducing medications (like letrozole)
• Dexamethasone and letrozole together = a significantly higher rate of pregnancy
o Improving metabolic status and reproductive dysfunction
o Reduces body weight, lowers blood pressure and serum insulin (Abstract truncated to 500 words)
