Poster Session Abstract Catalog
Hunter Pham
Michigan State University College of Human Medicine
Advisor: Andrew Jameson, MD
Authors: Hunter Pham, Andrew Jameson
“Oh by the way…”
Invasive salmonellosis, often linked to sickle cell disease or immunosuppression, was unexpectedly identified in a patient without any predisposing factors. The patient underwent hip arthroplasty, and a culture of the native hip synovial fluid revealed Salmonella enterica (serotype Reading). The critical discovery was possible due to a laboratory technician and a physician who maintained a high-quality relationship.
The case involved a 69-year-old male who sought care for persistent right hip pain. Despite receiving steroid injections for osteoarthritis, the pain persisted, leading to hip arthroplasty. During the procedure, the surgical team noted an unusual appearance of the synovial fluid, prompting them to send it for culture. Due to protocol technicality, the concerning fluid culture failed to be called as a critical result to the surgical team. Fortunately, it was brought to the attention of an infectious disease physician who had coincidentally visited the laboratory and engaged in conversation with his colleague who had identified the culture: “Oh, by the way… there’s this interesting culture you might want to see.” Recognizing the significance of the culture, the infectious disease physician alerted the patient’s surgical team and initiated antibiotic treatment.
This scenario both sheds light on the atypical spread of Salmonella enterica to a hip joint and underscores the importance of fostering strong interprofessional relationships in healthcare. A successful healthcare system relies on interdisciplinary collaboration, where professionals with different roles contribute equally to patient care. Deviating from this egalitarian approach leads to hierarchical systems that hinder teamwork and breed animosity between disciplines.
Natalie Nold
Chemical Engineering, Michigan Technological University
Advisor: Caryn Heldt, PhD
Authors: Natalie Nold, Grace James, Sheridan Waldack, Emily Agustin-Mazareigos, Trisha Colling, Taravat Sarvari, Amanda Bekkala, Lynn Manchester, & Caryn L. Heldt
Continuous Manufacturing for Viral Gene Therapeutics
Thirteen FDA approvals have been awarded and hundreds of clinical trials are underway for virus-based gene therapies. These novel vectors administer therapeutic genes by using a virus’s built-in delivery and infection hardware. Just two examples include Amgen’s herpes viral vector-based IMLYGICⓇ to treat melanoma and Spark Therapeutic’s adeno-associated viral vector-based LUXTURNAⓇ to treat retinal dystrophy. Unfortunately, gene therapies often cost over $1 million per dose due to high manufacturing costs for a single curative dose.
Continuously-processing manufacturing can reduce the cost of viral vector manufacturing by speeding process time and reducing manufacturing plant footprint. Our lab has developed a continuously-processing method using aqueous two-phase systems (ATPS) which combines product capture and purification by partitioning the viral product and contaminating host-cell proteins and DNA to different phases. ATPS relies on biocompatible and environmentally-friendly raw materials rather than expensive proprietary consumables such as chromatography resin, which translates into over 50% lower production costs compared to traditional processes at large manufacturing scales.
We have previously shown that porcine parvovirus (PPV), a non-enveloped vaccine model, can have a 66% recovery with over 90% removal of protein impurities and 94% host cell DNA after our two-stage process in batch mode. Now, we are developing our process to deliver high recoveries for adeno-associated virus (AAV) and herpes simplex virus (HSV), which are prominent gene therapy vectors. This proof-of-concept study demonstrates that a two-stage aqueous two-phase system could be incorporated into a fully-continuous purification process that will make viral manufacturing both more flexible and cost-effective.
Catherine Rono
Biological Sciences, Michigan Technological University
Advisor: Xiaohu (Mark) Tang, PhD
Authors: Catherine Rono, Xiaohu (Mark) Tang
Targeting phosphodiesterase: A potential strategy to treat LKB1-mutant cancers
Cancer heterogeneity poses numerous challenges to treatment, underscoring the need for personalized/targeted therapies that align with each patient's specific genetic and molecular disease profile. Metabolic deregulation, often correlating with oncogenic alterations, is commonly observed in cancers. Such deregulation frequently presents metabolic vulnerabilities within the cancer, which could potentially be exploited for targeted therapy. Liver Kinase B1 (LKB1), a protein known for its diverse roles in cellular metabolism and its critical function as a tumor suppressor, ranks as the third most frequently mutated gene in non-small cell lung cancer (NSCLC). LKB1 mutations are linked to accelerated tumor progression and invasion, resulting in adverse clinical outcomes. Our research uncovers a novel role for LKB1 in cyclic nucleotide metabolism, wherein it suppresses a set of phosphodiesterase (PDE) expressions. Specifically, LKB1 represses PDE3 via the activation of the downstream salt-inducible kinase. Our data demonstrate that PDE3 modulators can selectively eliminate LKB1-deficient tumor cells while leaving LKB1-wildtype cells unharmed. However, some LKB1-deficient cells develop resistance due to the loss of SLFN12, whose expression is required for PDE3 modulator-induced cell death. Interestingly, this resistance can be overcome by inducing SLFN12 expression, through either epigenetic inhibitors or cAMP inducers. These findings not only broaden our understanding of the role of LKB1 in metabolic regulation but also suggest a promising strategy for targeted therapy against LKB1-mutant cancers.
Abel A Reyes-Angulo
Applied Computing, Michigan Technological University
Authors: Abel Reyes-Angulo, Sidike Paheding
Explainability of Deep Learning Models for Melanoma Segmentation: A New Perspective from Compound Loss Function.
Melanoma is one of the deadliest forms of skin cancer in the USA, with a survival rate of 23% for delayed diagnosis. However, early detection could extend the survival rate up to 99%. Due to the importance of early analysis of skin lesions, many efforts have been dedicated to implementing end-to-end automated artificial intelligence systems to detect the presence of melanoma. In this study, we investigate a series of loss functions that have been used to train deep learning models for medical image analysis, from an aspect of explainability. Then, we propose a set of weighted compound loss (WCL) functions to improve the segmentation performance of a U-Net-based deep learning model for Melanoma detection. In this research, two popular and publicly available skin lesion datasets are utilized: the ISIC 2016 and the HAM10000 datasets. The Grad-CAM technique is employed to provide interpretability analysis to the proposed research. The results showed that our proposed WCL outperformed the other traditional loss functions in terms of overlap-based and region-based metrics, such as mean intersection over union (mIoU) and pixel accuracy, and also showed better promises in terms of explainability results.
Derrick Simet
Kinesiology and Integrative Physiology, Michigan Technological University
Advisor: Qing-Hui Chen, MD, PhD
Authors: Derrick Simet, Andréa R. Collins, Andrew D. Chapp, Gregory Miodonski, Michael Huber, Mingjun Gu, Zhiying Shan, Qing-Hui Chen
Inhibiting Local Brain Metabolism of Ethanol in The Central Nucleus of The Amygdala Blunts Sympathoexcitatory Effects of Ethanol in Sprague Dawley Rats
Binge alcohol consumption leads to robust sympathoexcitation and excitatory neuronal output. However, the central mechanism that mediates these effects remains unknown. We hypothesized that local brain metabolism of ethanol to acetic acid/acetate in the central nucleus of the amygdala (CeA) would drive in vivo sympathetic nerve activity (SNA) through activation of N-methyl-D-aspartate receptors (NMDAR). Furthermore, inhibiting local CeA ethanol-metabolizing enzymes or NMDAR antagonists would blunt the sympathoexcitatory effect of ethanol and acetate. We demonstrate that in Sprague Dawley rats, local brain metabolism of ethanol in the CeA to acetic acid/acetate elicits sympathoexcitatory responses in vivo through activation of NMDAR. Alcohol dehydrogenase or aldehyde dehydrogenase
inhibition using fomepizole or cyanamide and NMDAR antagonism using AP5 or memantine blunted the effects of ethanol and acetate, respectively. Fomepizole or cyanamide microinjected into the CeA had no effect on altering baseline SNA, and cyanamide did not impact the sympathoexcitatory effect of acetate. These findings suggest that within the CeA, ethanol is sympathoexcitatory through local brain metabolism, which generates acetic acid/acetate leading to activation of NMDAR. Understanding potential active metabolites of ethanol and
their mechanism of action may be beneficial for treating alcohol use disorder and its cardiovascular sequelae.
Henry Summers
Materials Science & Engineering, Michigan Technological University
Advisor: Jaroslaw Drelich, PhD
Authors: Henry D. Summers, Morteza S. Ardakani, and Jaroslaw W. Drelich
Corrosion-Fatigue Response of a Novel Zn-Based alloy for Bioresorbable Stents
To date, the cyclical fatigue behavior of bioresorbable Zn-based alloy systems has not received substantial attention by researchers working to advance the development of temporary metallic stents. Cyclical pressures that are imposed onto an implanted stent by the arterial pulsation from a patient’s heartbeat are a source of potential premature failure in these devices, especially when paired with degradation from a physiological environment. Of interest are the impacts of secondary phases present in the microstructure of hot-extruded zinc alloys on the corrosion-fatigue performance. Characterization of these effects is performed using an annealing heat treatment to vary the volume fraction of secondary phases, which is observed and quantified with both optical and scanning electron microscopy (SEM). Fatigue experiments are conducted on samples in as-extruded and annealed conditions. Physiological conditions are simulated by immersing the samples in a body-temperature Hank’s balanced salt solution during fatigue tests, which are compared with similar tests in air. Fracture surfaces are observed with SEM to identify differences in fracture mechanisms caused by microstructural and environmental variables. It is revealed that the annealing treatment results in a slight improvement in fatigue strength. Fatigue strength is drastically reduced in the Hank’s solution due to the worsened mechanical integrity associated with coupled effects of cyclical loading and corrosion.
Sydney Brief
Michigan State University College of Human Medicine, Spectrum Health, Department of Emergency Medicine
Advisor: Dr. Jeff Jones
Authors: Sydney Brief, Jon Giolitti, Abbigail Behmlander, Emma Dixon, Sydney Hudock, Linda Rossman NP, Stephanie Solis NP, Meredith Busman MD, Lisa Ambrose MS, Lindsey Ouellette MS, Jeffrey S Jones MD
Comparative Analysis of Digital Camera Systems for the Documentation of Anogenital Injuries Following Sexual Assault
Background: Colposcopy is now the standard of care in sexual assault examination throughout the United States. However, current technology has limited accuracy and poor interobserver agreement for the classification and location of anogenital injuries.
Methods: This was a retrospective, before-and-after trial to assess genital injuries in consecutive adult women presenting after sexual assault to a freestanding nurse examiner clinic (NEC) during a 3-year study period. Patients evaluated in 2016-2017 had injuries documented using a Cooper Surgical Leisegang© colposcope system. Those seen during 2019 had injuries documented using the high-resolution camera system. The primary outcome of interest was the frequency of genital findings documented in sexual assault victims from each group. Descriptive statistics were used to summarize the frequency of anogenital injury, location, and type of injury.
Results: A total of 367 women were evaluated during the “before” period and 180 in the “after” period. The two groups were comparable in demographics, assault history, time to examination, and the frequency of nongenital injuries. Patients examined using the high-resolution camera system had significantly greater mean genital injuries documented (2.4 vs. 1.9, p = 0.013). However, most of these injuries were superficial abrasions not visible to the naked eye.
Conclusions: The findings indicate that the identification of anogenital injuries differs based on the imaging system employed. The additional genital injuries detected by the high-solution camera system were superficial abrasions not visible to the naked eye. This microtrauma is unlikely to have any clinical importance in treatment or relevance to criminal prosecution.
Lindsay Sandell
Michigan State University College of Human Medicine
Advisor: Dr. Mark Trottier
Authors: Lindsay Sandell, Sydney Rechner, Mark Trottier
Regional Needs Assessment of Bleed Control Training in Upper Peninsula of Michigan School Systems
Background: Bleed control (B-CON) training for K-12 schools is an emerging public health focus. This study investigates schools in the Upper Peninsula of Michigan, a uniquely isolated rural region without a Level 1 trauma center. In this region, all school nurses were B-CON trained to increase safety and potentially serve as a conduit for school training.
Methods: This was a study of public school superintendents, principals, and school nurses. Schools were administered a phone survey regarding current B-CON program strategies, interest, and perceived barriers to implementation. Notes were taken to analyze overall themes related to B-CON training.
Results: A total of 20 interviews were conducted (37% response rate for 57 schools contacted). Respondents included superintendents (60%), nurses (25%), and principals (15%). 40% of schools indicated they have bleed control training in place for faculty and staff. Of schools without training, 58% of schools expressed interest in receiving it. While nurses were trained in B-CON, only 50% of the schools employed a nurse. Also, the presence of a school nurse was not associated with having existing B-CON training. 65% of schools reported having a community resource (local hospital, health department, sheriff office) for assistance. Lack of time and financial resources were reported as barriers to B-CON implementation.
Conclusions: In the Upper Peninsula of Michigan, increased collaboration between schools and the community is essential to increase B-CON training. Suggestions for improvement include leveraging existing trained school nurses and organizing the use of community resources.
Jenna Disser
Biological Sciences, Michigan Technological University
Advisor: Robert Larson, PhD
Authors: Jenna R. Disser, Qing-Hui Chen, Robert A. Larson
PVN SK channel blockade alters sympathetic nerve bursting pattern in angiotensin II-infused rats
Sympathetic nerve activity (SNA) demonstrates rhythmic activity through integration of signals from lung inflation afferents, baroreceptor afferents, and respiratory neurons in the brainstem that influence presympathetic neurons in the rostral ventrolateral medulla (RVLM). The paraventricular nucleus (PVN) is a regulatory center for SNA and PVN neurons have axon projections to the RVLM. Blockade of small conductance calcium-activated potassium (SK) channels in the PVN significantly increases splanchnic and renal SNA. The aim of this study was to determine the influence of chronic AngII infusion on SNA firing patterns before and after PVN SK channel blockade with apamin. Experiments were performed in ventilated, male Sprague-Dawley control (Ctrl; n=5) rats, or rats infused with AngII (150 ng·kg −1 ·min −1 ) for 2 weeks (n=4). Power spectral density was calculated on 5-minute segments of SNA at baseline, and during the maximum response to apamin. Splanchnic and renal SNA spectral power in the 0-2Hz (low) frequency band was similar between Ctrl and AngII rats at baseline. PVN apamin significantly increased spectral power in the 0-2Hz band similarly in both groups. In contrast, baseline spectral power in the 5-7Hz (cardiac) frequency band was significantly higher in AngII rats compared to control for splanchnic and renal SNA. Interestingly, PVN microinjection of apamin significantly attenuated spectral power in the 5-7Hz band in the AngII group alone for splanchnic and renal SNA. In conclusion, PVN SK channel blockade shifts the SNA burst
pattern in both Ctrl and AngII rats towards lower frequencies bursts known to have a greater influence on vascular tone.
Abigail Brooks
Kinesiology and Integrative Physiology, Michigan Technological University
Advisor: Steven Elmer, PhD
Authors: Abigail C. Brooks, Isaac M. Lennox, Isaac J. Wedig, Steven J. Elmer
Promoting Physical Activity in the Rural and Medically Underserved Upper Peninsula of Michigan
Physical inactivity poses a major public health problem as 80% of U.S. adults do not meet the physical activity guidelines. Further, physical activity levels are lower in rural areas like the Upper Peninsula of Michigan which is a rural and medically underserved region. The beneficial effects of physical activity remain underestimated by the medical community, policy makers, and public at large. The purpose of this community outreach project was to implement an Exercise is Medicine® on Campus (EIM-OC) program at Michigan Technological University to provide physical activity resources to the campus and broader community. A team of students, faculty, and fitness professionals: 1) promoted physical activity through a widespread media campaign (i.e., website, social media) and 2) delivered over 300 virtual home-based workouts to community members using several platforms (i.e., Zoom). Together, these efforts highlight the extent to which EIM-OC bolstered physical activity infrastructure for our rural and medically underserved region. Current efforts of the program include establishing physical activity as a vital sign of health during patient exams in the student health clinic on campus and distributing an exercise DVD to the members of the community. Physical activity is a robust form of medicine to help prevent and treat both chronic and infectious disease. For substantial health benefits adults of all ages should engage in at least 150 min of moderate-to-vigorous intensity physical activity each week (~20 min/day) and limit time spent sitting. Importantly, any amount of activity, even below the ideal range, provides health benefits.
Vedant Buwa
Chemistry, Michigan Technological University
Advisor: Marina Tanasova, PhD, Smitha Rao, PhD
Authors: Vedant Buwa, Marina Tanasova
Establishing the impact of GLUT5 targeting specific probes on cytotoxicity of cisplatin in cancer cells.
The elevated uptake and metabolism of glucose has long been a recognized hallmark of cancer, imparting crucial insights into tumorigenesis and therapeutic prospects. The Warburg effect, characterized by heightened glucose consumption by cancer cells, has driven extensive research targeting various facets of glucose metabolism through receptor, transporter, and enzymatic interventions.
In this context, coumarin glycoconjugates have been used as a framework for developing fluorescent probes, facilitating the monitoring of glucose transporter dynamics. Particularly pertinent are the GLUT5-specific glycoconjugates, which exhibit rapid accumulation within GLUT5-positive cancer cells, effectively serving as surrogate indicators of transporter activity.
This study unveils the sustained engagement with GLUT5, resulting in prolonged cytotoxic impact within GLUT5-positive malignancies, thereby augmenting the therapeutic efficacy of cisplatin across a diverse spectrum of cancer cell lines. By harnessing GLUT5 as a strategic target, this research introduces a novel avenue for refining cancer therapies and underscores the potential synergy between glycoconjugates and conventional chemotherapeutics. Through elucidating the intricate relationship between glucose metabolism and targeted cytotoxicity, this investigation lays the groundwork for advancing precision oncology and fostering innovative therapeutic strategies.
Aimee Marceau, PhD
Lab Lead/Scientist, Michigan Technological University
Authors: Aimee H. Marceau, Trisha Colling, Hamid Ismail, Garrett Kucharski, Dukka KC, Stephen Techtmann, Kristin Brzeski
Identifying Tick borne disease in the UP
Tick-borne illnesses are a continuing and emerging source of disease in the Upper Peninsula. Using the resources provided by the MI-SAPPHIRE grant, the Genomic Sequencing lab at Michigan Tech has established a program to crowd-source ticks for disease surveillance. This program successfully combined modern disease surveillance techniques with community engagement to identify common tick-borne diseases and specific areas of disease prevalence. Our work suggests that tick-borne illnesses are more common in the Upper Peninsula than previously thought. Deep sequencing of tick samples will provide important insights into the lineage, the prevalence of antibiotic resistance, and the diversity of diseases carried by ticks in the UP.
Sriram Malladi, PhD
Mechanical Engineering-Engineering Mechanics, Michigan Technological University
Authors: Vijaya V N Sriram Malladi, Caroline Gwaltney, Smitha Rao, Erin Buckeridge, Chad Garton
Non-Intrusive Gait Analysis via Innovative Floor-Mounted Accelerometers
Gait analysis, a crucial tool in health assessment, finds diverse applications in clinical and research contexts. While traditional methods such as 3D motion capture offer precision, their cost limits their use to research settings. Our study introduces an innovative gait analysis approach using floor-mounted accelerometers. Our novel approach harnesses floor vibrations for continuous gait parameter extraction, obviating the need for wearables and ensuring user-independent data collection.
Our objective is to compute and assess gait parameters like average stride length, step timing, foot-step forces, and step signal energy, all derived from detected footsteps. Additionally, we will create distributions for participants' measured gait parameters. Our research resonates with the conference themes of rural health/healthcare and interdisciplinary collaboration. By circumventing wearables, our method provides a cost-effective, non-intrusive way to assess gait, especially in rural or resource-limited settings. Moreover, our innovative methodology bridges healthcare and engineering disciplines, showcasing the potential of interdisciplinary collaboration.
In conclusion, our study pioneers a technique utilizing floor-mounted accelerometers for gait analysis, offering a non-intrusive, cost-effective solution with broad clinical relevance. We eagerly anticipate presenting our findings at the Upper Peninsula Medical Conference's poster session, enriching discussions on rural health and interdisciplinary collaboration.
Haley Marchese
Biological Sciences, Michigan Technological University
Advisor: Robert Larson, PhD
Authors: Haley M. Marchese, Jenna R. Disser, Robert A. Larson
Sympathetic Activity to the Heart is Increased in a Mouse Model of Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by abnormally thick cardiac muscle and an increased risk of arrhythmias and sudden cardiac death. Studies in humans have demonstrated decreased beta-1 adrenergic receptor (B1R) expression in the left ventricle (LV) and increased cardiac norepinephrine spillover and in HCM. We have previously demonstrated increased cardiac sympathetic tone in an alpha-tropomyosin mutant mouse model of HCM. The aim of this study is to further characterize cardiac and autonomic function in HCM mice. First, we recorded left ventricular pressure in male HCM and littermate wild-type (WT) control mice (n=5 mice each group) anesthetized with isoflurane (2% in O2). Heart rate (HR) was significantly (p<0.05) lower in HCM (438±22 beat/min) compared to WT (525±6 beat/min) mice. Similarly, dP/dt max was also significantly (p<0.05) reduced in HCM (5857±452 mmHg/s) compared to WT (7684±258 mmHg/s) mice. Next, we utilized western blot to measure protein expression in LV tissue from HCM and littermate WT mice. Results are expressed relative to WT mice (n=4 male mice in each group). B1R expression was significantly reduced in the left ventricle (LV) of HCM mice compared to WT littermate controls (HCM 60±1 vs. WT 100±4; p<0.05). Tyrosine hydroxylase (TH) protein expression (standardized to cardiac neuronal content with PGP9.5) was significantly higher in the LV of HCM mice compared to WT mice (HCM 135±15 vs. WT 100±1; p<0.05). In conclusion, our findings suggest that cardiac and autonomic abnormalities are consistent between HCM mice and humans.
Katy Matson
Biological Sciences, Michigan Technological University
Advisor: Xiaoqing Tang, PhD
Authors: Katy Matson, Aaron MacLeod, Nirani Mehta, Ellie Sempek, and Xiaoqing Tang
miR-483 deficiency induces beta-cell dedifferentiation and oxidative stress
Beta-cell dedifferentiation is a pathological mechanism that contributes to the loss and dysfunction of beta-cell during the progression type 2 diabetes (T2D). However, the specific processes involved in these cell conversions are still being analyzed. MicroRNAs (miRNAs) have been shown to play a crucial role in controlling the function of beta-cells in response to metabolic changes. We previously identified higher expression of miR-483 in beta-cells compared to alpha-cells, and mice with beta-cell specific deletion of miR-483 (miR483-/-) exhibited high fat diet (HFD)-induced hyperglycemia and reduced glucose tolerance. HFD-fed miR483-/- mice exhibited elevated expression of aldehyde dehydrogenase family 1, subfamily A3 (Aldh1a3), a beta-cell dedifferentiation marker. In this study, we further detected increased plasma glucagon in miR483-/- mice treated with HFD and/or streptozotocin (STZ) when compared to miR483+/+ control mice, and glucagon contents were also increased in isolated islets of miR483-/- compared to control islets when treated in palmitate plus cytokine. Lineage tracing studies identified that all ALDH1A3-positive cells were colocalized with the beta-cells reporter YFP, and a significant number of ALDH1A3-positive beta-cells failed to detect insulin in miR483-/- mice. Moreover, a higher proportion of ALDH1A3-positive beta-cells were colocalized with glucagon in miR483-/- mice compared to control mice, implying miR-483 deletion promotes beta-cell dedifferentiation or transdifferentiation into alpha-cells. In addition, we found that loss of miR-483 significantly increased multiple enzymes involved in adaptive oxidative stress, potentially leading to mitochondrial dysfunction. Our data indicates that miR-483 is vital for protecting beta-cell identity, and miR-483 deficiency induces beta-cell dedifferentiation and oxidative stress.
Fatemeh Razaviamri
Biomedical Engineering, Michigan Technological University
Advisor: Bruce P. Lee, PhD
Authors: Fatemeh Razaviamri, James Manuel, Bruce P. Lee
Film-forming halogenated catechol-functionalized gelatin nanoparticles for hemostasis and wound healing applications
Bleeding wounds pose hemorrhagic or hypovolemic shock risks, with up to 40% of trauma deaths due to bleeding. Wound infections kill millions due to pathogen growth in damaged skin. Untreated, they spread, causing organ failure and death. Most infections are challenging to treat due to the unprecedented speed of their transmission or drug resistance. designing a robust and antibacterial hemostatic agent can address both above-mentioned challenges. Hemostatic powders are portable hemostatic agents that can be functionalized with antimicrobial agents. Herein, utilizing the mussel adhesive chemistry, halogenated catechol-functionalized gelatin nanoparticles were prepared through the electrospray approach as hemostatic powders to form a film upon contact with blood and use for (a) rapid and effective hemostasis to decrease blood loss in the bleeding wound, (b) bacteria-infected wound healing, and (c) antimicrobial applications.
Lucas Sheppard
Chemistry, Michigan Technological University
Advisor: Tarun Dam, PhD
Authors: Lucas Sheppard, Olivia Hohman, Purnima Bandyopadhyay, Tarun K. Dam
A broad spectrum natural cytotoxin with therapeutic potential
The plant kingdom has been a perpetual source of medicinally important biomolecules. From the chemotherapeutic drug Paclitaxel (Taxol) to the Nobel prize winning anti-malarial drug Artemisinin, numerous therapeutics have been discovered in plants. Many of these biomolecules act by stopping cell division or by directly killing targeted cells. We recently found and characterized a highly potent cell-killing (cytotoxic/cytolytic) biomolecule, named CDC-X, from a flowering plant species. Our poster will show that CDC-X can efficiently kill two different types of breast cancer cells, fungal cells, and bacterial cells (E. coli). We will present evidence to show that CDC-X binds to the surfaces of the target cells, alter the surface structures to make the cell membranes porous, and ultimately fragment the cell boundaries to kill the cells. Given its anticancer, antifungal, and antibacterial properties, CDC-X is very much relevant to public health and its clinical applicability is significantly high. We are currently determining the structure of CDC-X through interdisciplinary collaborations and will test the applicability of CDC-X by collaborating with clinicians and pharmaceutical companies.
Devrim Yagmur Durur
Chemistry, Michigan Technological University
Advisor: Ashutosh Tiwari, PhD
Authors: Devrim Yagmur Durur, Connor Hall, Emily Davis, Jenna Cunnien, Ashutosh Tiwari
Lysozyme Aggregation in Different Environmental Conditions: A Biophysical Analysis
Neurodegenerative disorders, such as Alzheimer’s disease, are characterized by protein misfolding and aggregation, which result in the deposition of abnormal protein aggregates and the development of neurotoxicity. Early aggregation events have been shown to affect the structure of mature aggregates in some disease-related proteins, which may influence their toxicity. Disease proteins' structure and biophysical characteristics, such as hydrophobicity and flexibility, are influenced by their physicochemical environment, which includes factors like pH, temperature, and agitation. Therefore, it is important to understand the various properties aggregates may possess in response to a changing environment and whether these properties can be linked to higher levels of toxicity.
In this study, the model protein lysozyme was examined at varying relevant pHs and agitation levels to simulate natural cellular movement as well as pHs observed in different organelles (e.g., cytosol, lysosomes, or mitochondria). Different methods were used to monitor lysozyme’s aggregation kinetics, its unique physicochemical properties, and its morphology as a function of time. According to our findings, there are significant differences in the size and compactness of the aggregate morphology of lysozyme. Interestingly, some aggregates experience size reduction and an increase in compactness over much shorter periods of time than others. However, based on their morphology, all aggregates are categorized as having an amorphous structure across all experimental conditions examined here. They are currently being evaluated to see if these variations in aggregate size as well as differences in their physicochemical properties modulate cytotoxicity.
Isabella Purosky
Michigan State University College of Human Medicine
Advisor: Dr. Lisa M. Lowery
Authors: Isabella R. Purosky, MS2
Differences in Adolescent Mental Health Screening Results between Suburban and Urban Demographics
Pediatric mental health screenings involve the Patient Health Questionnaire (PHQ). Suicide rates for children and adolescent suicidal prevalence has been on the rise,2 especially since COVID3. Research was conducted at Rockford Pediatrics, with the expected trend that positive tests would increase from 2019 to 2022.4 Such an increase was not noted at Rockford Pediatrics. To our knowledge, there has been no literature highlighting the difference between suburban and urban demographics.
This is a retrospective study assessing past PHQ scores from Rockford Pediatrics, a northeast suburb of Grand Rapids, MI, and Academic General Pediatrics (AGP) Residency, a practice in downtown Grand Rapids, MI. Dates utilized were between 01/02/19-12/31/19 and 01/03/22-12/07/22. De-identified data extraction was done for patients ages 11-18 years old utilizing Office Practicum (Rockford) and SpicerDicer on Epic (AGP).
The AGP clinic had a noted increase in the number of positive PHQ-9 scores 2019 to 2022; while Rockford did not. At Rockford Pediatrics in 2022, there was an overall 77% White Non-Hispanic population. At AGP there was a 14% overall White Non-Hispanic population. The white population at (AGP) had a significant increase in positive PHQ-9 scores, but the white population at Rockford had a significant decrease. Populations of color at AGP showed a drastic increase in positive PHQ scores from 2019 to 2022 in comparison to the white population.
Due to the results, socioeconomic factors beyond race/ethnicity come into question. Further research includes investigating zip-codes to isolate these factors.
Resources:
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Meherali, S.; Punjani, N.; Louie-Poon, S.; Abdul Rahim, K.; Das, J.K.; Salam, R.A.; Lassi, Z.S. Mental Health of Children and Adolescents Amidst COVID-19 and Past Pandemics: A Rapid Systematic Review. Int. J. Environ. Res. Public Health 2021; 3432(18) 3432. doi:10.3390/ijerph18073432
(n.d.). Mental Health Screenings. National HIV Curriculum. Retrieved January 9, 2023, from https://www.hiv.uw.edu/page/clinical-calculators/apri
Stier, A.J., Schertz, K.E., Won Rim, N., Cardenas-Iniquez, C., Lahey, B.B., Bettencourt, L.M.A., Berman, M.G. Evidence and theory for lower rates of depression in larger US urban areas. Journal of Proceedings of the National Academy of Sciences (PNAS). 2021; 118(31):e2022472118. doi: 10.1073/pnas.2022472118.
Alexandra Little
Kinesiology and Integrative Physiology, Michigan Technological University
Advisor: Carolyn Duncan, PhD
Authors: Alexandra Little, Gracie VanLangevelde, Lily Hart, Cameron Williams, Todd Hall, Carolyn Duncan
Utilizing Surface Electromyography and Kinematic Analyses to Quantify Deep Tendon Reflexes
Deep tendon reflexes (DTRs) are a fundamental part of neurological examinations. Clinical observations and past studies have suggested that abnormal DTRs are a sign of corticospinal tract abnormalities or dysfunction with other descending pathways that influence the reflex arc. However, there are challenges regarding the interpretation and understanding of reflex excitability in clinical settings. There have been some attempts at using alternative methods, such as electromyography, to mechanically quantify DTRs for interpretation. However, this research has been limited to smaller focused studies and has not been used to examine and characterize DTRs across larger populations.
The overarching goal of the research is to characterize and quantify DTR responses using surface EMG and kinematic analyses. To accomplish this our research team is currently performing 2 studies that aim to 1) Quantifying and determining the repeatability of DTR in healthy varsity athletes 2) Evaluating the relationship between neuromuscular output and DTR rating and 3) Examining the influence of concussions and contact sports on DTR response. In all studies surface EMG electrodes and inertial measurement units (IMU) are utilized to help quantify responses during standard quadriceps, achilles, biceps, and triceps DTR testing. While this research is currently ongoing, initial findings suggest that surface electromyography and kinematic analyses can provide more precise information about DTR responses. Moving forward, these initial findings provide the foundational basis for future research examining DTR responses. This research also demonstrates the potential for utilizing EMG and kinematic analyses in clinical settings to gain more information about DTR responses.
Parisa Abadi, PhD
Mechanical Engineering-Engineering Mechanics, Michigan Technological University
Authors: Parisa Abadi, Nishaki Mehta, Erico Freitas, Daniel Sigg, Lars Mattison, Roya Bagheri, David Haines
Ultrastructural Observations in the Porcine Atrial Myocardium Following Pulsed Field Ablation
Pulsed field ablation (PFA) is an attractive new ablation modality given its relative non-thermal and cardioselective properties. However, the exact mechanism of atrial myocyte destruction in vivo has not been fully characterized. Here, we report the ultrastructural properties of atrial myocardium in central and border zone tissue following PFA in an acute porcine model. Four pigs were studied. A PVAC GOLD catheter was placed in the superior vena cava (SVC), right atrium (RA), left atrial appendage (LAA) and right pulmonary vein (RPV). One and four trains at 1000 V and 1500 V were delivered at these four sites in a random fashion. Within 4-5 hours of PFA delivery, ablation lesions were sectioned in the center (C), at the border zone (BZ) and remote from the acute lesion (R) in the myocardium. Light microscopy (LM) and transmission electron microscopy (TEM) were done at these 3 regions using standard procedures. Briefly, the tissue pieces were chemically fixed, dehydrated in alcohol, and embedded in an epoxy resin. Then, using a microtome, 600 and 85 nm sections were cut for LM and TEM, respectively. The sections were stained using toluidine blue for LM and uranyl acetate and lead citrate for TEM followed by imaging. Electron microscopy demonstrated the presence of significant abnormalities of the plasma membrane, mitochondria, and sarcomeres in the ablated regions. The sarcomeres appeared particularly sensitive to PFA and were highly damaged in large areas of the cells at the BZ and C regions. The R region had significantly less damage.
Olivia Hohman
Chemistry, Michigan Technological University
Advisor: Tarun Dam, PhD
Authors: Olivia Hohman, Lucas Sheppard, Purnima Bandyopadhyay, Tarun K. Dam
Detection of disease-related biomarkers by a simple method
Biomarkers are life savers because they help detect diseases early. Many of the cancer biomarkers listed by the Food and Drug Administration are glycoproteins. Glycoprotein biomarkers include Haptoglobin (Hp) [for various types of cancer including prostate cancer], α2-macroglobulin [for bladder cancer], Thyroglobulin (Tg) [for thyroid cancer], Alpha-fetoprotein (AFP) [for hepatocellular carcinoma], β-human chorionic gonadotropin (β-hCG) [for testicular and ovarian cancers], CA 15-3 [for breast, prostate cancers], CA 19-9 [for gastrointestinal and pancreatic cancers], CA 125 [for ovarian cancer], carcinoembryonic antigen (CEA) [for colorectal cancer], and prostate-specific antigen (PSA) [for prostate cancer]. Given the clinical importance of biomarkers and the challenges associated with their detection, public health can always benefit from new and efficient detection methods for biomarkers. Utilizing our expertise in glycobiology, we have developed a simple and rapid method for glycoprotein detection and applied that method to detect biomarkers from blood samples. Our method successfully detected several important biomarkers including Haptoglobin, Thyroglobulin, α2-macroglobulin, Alpha-1 antitrypsin, and Histidine-Rich Glycoprotein (HRG). Besides being cancer biomarkers, Haptoglobin and α2-macroglobulin also serve as markers of inflammatory bowel disease, while Alpha-1 antitrypsin is a biomarker of metabolic diseases. HRG is a biomarker of pre-eclampsia, sepsis, and postoperative complications in intensive care unit patients. Our method was also able to detect Galectin-3, which is a cardiovascular and cancer biomarker. The ability to detect disease related biomarkers makes our method highly applicable in clinical settings and relevant to public health. We are setting up collaborations with clinicians to further validate our method by using patient samples.
Alexander Stamm
Michigan State University College of Human Medicine
Advisor: Erich Petushek, PhD
Authors: Alex Stamm, Kim Santiago, Chris Kuenz
Latent Profile Analysis of Patient Reported Outcomes Following ACL Reconstruction
Anterior cruciate ligament reconstruction (ACLR) is one of the most common orthopedic procedures in the world. ACLR is commonly performed in patients who are active in sports, with the goal of returning the patient back to the same state as they were pre-injury. Unfortunately, many athletes still do not return to sport (RTS) following a traumatic knee injury such as this. The exact cause of the return to sport (RTS) variability in each patient is hard to pinpoint, but one factor of concern is the psychological aspects of such recovery.
The purpose of this study is to use Latent Class Analysis (LCA) to characterize unique clustering of reasons why athletes do not return to their pre-injury activity level after ACLR. It is believed that individuals with high pain scores and high levels of fear would be less likely to return to pre-injury activity level. In this study, patients at a single institution who underwent primary ACLR from 2005-2021 were contacted to complete a survey. Patients’ ability to RTS and pre-injury activity level, reasons for inability to return to pre-injury activity level, and patient reported outcome scores were collected from. LCA was performed to identify and compare patterns among patients’ reasons for not returning to preinjury activity level. Patients were differentiated into three distinct classes following primary ACLR, and those with patient-reported characteristics of pain, lack of strength, instability, or fear were far less likely to return to preinjury activity level or sport.
Xinqian Chen
Kinesiology and Integrative Physiology, Michigan Technological University
Advisor: Zhiying Shan, PhD
Authors: Xinqian Chen, Xin Yan, Leah Gingerich, Qinghui Chen, Lanrong Bi and Zhiying Shan
Brain-derived extracellular vesicles from Dahl salt sensitive rats with high salt diet induce inflammation and oxidative stress
Hypertension (HTN), a leading risk factor for cardiovascular diseases, involves various contributing factors such as excessive dietary salt intake. Multiple mechanisms have been proposed to contribute to salt sensitive HTN, including inflammation and oxidative stress. Recent advances in cell-to-cell communication have been brought to the attention of extracellular vesicles (EVs), as well as their role in inflammation and oxidative stress. EVs, naturally secreted by almost all cell types, can encapsulate a broad spectrum of biological molecules and ferry these contents to the local and distant recipient cells. Under disease conditions, EVs derived from diseased cells can lead to diverse responses and behavioral changes in recipient cells by translocating cell-type-specific cargos. So far, the understanding of EVs in hypertension and its relevant mechanisms remains limited, especially their roles in the brains under hypertensive development. To expand our knowledge, our research group proposed that brain-derived EVs contribute to neuroinflammation and oxidative stress under hypertensive development. This hypothesis was tested using EVs from normotensive Sprague Dawley rats (SD-EV) and hypertensive Dahl salt sensitive rats (DSS-EV). DSS-EV and SD-EV were incubated with primary neurons or injected into the brain lateral ventricle of normotensive rats. Current results showed that EVs derived from the brains of hypertensive rats increased mRNA levels of inflammatory cytokines and chemokines, as well as oxidative stress, in primary neurons and/or specific brain region (the paraventricular nucleus of hypothalamus). We hope these EV-related processes can provide insights into the potential therapeutic targets for hypertension and related diseases.
Quality Improvement Project Posters
Dr. Zachary Greenlee
Resident Physician, UP Health System-Marquette
Authors: Dr. Zachary Greenlee, Dr. Sarah Naracon
Bipolar disorder screening prior to initiating pharmacotherapy in outpatients presenting for new onset mood symptoms
Dr. Andrew Layne
Resident Physician, UP Health System-Marquette
Authors: Dr. Andrew Layne and Dr. Cecil Brown
Improving compliance to early ambulation in the inpatient setting
Dr. Kelley Mahar
Associate Program Director, MSU Psychiatry Residency UP Track, MSU / UPHEC / UPHS
Authors: Dr. Kelley Mahar, Dr. Stuart Johnson, Daniel Brown
Access to behavioral healthcare: Interprofessional psychiatric telephone consultation for primary care providers
Dr. Russell Reeves
Resident Physician, UP Health System-Marquette
Authors: Dr. Russell Reeves, Dr. James O’Brien, Dr. Logan Hanert
Implementing the AIMS exam in a family practice clinic
Dr. Erin McKenzie
Resident Physician, UP Health System-Marquette
Authors: Dr. Erin McKenzie, Dr. Gabrielle McGrath
Caprini score documentation and utilization in care decisions by intra-hospital teams