Student and Resident Research
During the summer between the first and second year of their medical studies, AU/UGA Medical Partnership students are encouraged to engage in a scholarly activity which could include laboratory science or clinical research. Students more interested in a participatory clinical experience are also encouraged to engage in "inquisitive observation and reflection" in order to derive a more complete understanding of health problems within the context of the greater community.
Medical Partnership students travel far and wide to work with mentors in a variety of specialties. While some students chose to stay in Athens or Augusta, others conduct research at academic institutions, hospitals, and clinics across the United States. Several students have participated in projects that took them to third world countries where they assisted physicians with caring for patients with limited access to healthcare.
Each fall, the Medical Partnership hosts a Student Research Symposium that showcases the activities of students who participated in a summer project. Students present posters representing the results of their summer endeavors.
Residents in the Medical Partnership’s sponsored and affiliated Internal Medicine residency training programs are engaging in patient-oriented research. These projects develop out of the questions that arise during the care of patients, and have primarily focused on improving the quality of care and improving patient safety.”
Some of the research conducted during the 2016 summer is featured below. The Medical Partnership student names are underlined and in italics.
Androgenic to estrogenic switch in human adult prostatic tissue: Opportunities for personalized care for patients with BPH
Jonathan Pham (1,2), R. Ge (3), L. Hu (3), Z. Wang (2), Aria F. Olumi (3,4)
Benign prostatic hyperplasia (BPH) is a global health problem affecting more than 90% of men over the age of 80. Progressive enlargement of the prostate gland, the only solid organ that grows during adulthood, has been linked to bladder outlet obstruction and irritative lower urinary tract symptoms that can impact an individual’s quality of life and in severe cases, lead to irreversible bladder dysfunction and renal failure due to inadequate emptying of urine. Despite their widespread use and clinical effectiveness, 25-30% of patients are resistant to the therapeutic effect of 5-alpha reductase inhibitors, medications that target the gene responsible for development and growth of prostate. We have found the 30% of adult men do not express 5-alpha reductase 2 due to epigenetic changes associated with the gene that are mediated via inflammatory mediators like Tumor Necrosis Factor-alpha (TNFa). The purpose of this study was to elucidate the alternative pathways when 5-alpha reductase 2 is silenced.
This study focused on SRD5A2 and aromatase, enzymes that contribute to prostate development and growth. Prostate stroma cells were cultured and treated with varying concentrations of TNFa. RNA was extracted via RNA Shredder and RNAeasy kit. The resulting RNA was analyzed using a one step qPCR to determine relative gene expression between the samples. Data was compared to a control using the ΔΔCT method.
The initial results indicated that treatment with TNF can yield a 2-fold decrease in SRD5A2 expression in stroma cells while resulting in an decrease expression of aromatase. This suggests that in human adult prostates, TNF may contribute to SRD5A2 expression and prostatic growth in patients. Overall, a better understanding of epigenetic changes that affect SRD5A2 and aromatase expression in the prostate will have broad implication for offering personalized care for patients suffering from BPH.
1 Augusta University/University of Georgia Medical Partnership, Athens, Georgia; 2 Herbert Brendler, MD Summer Medical Student Fellowship Program, American Urological Association, Linthicum, Maryland; 3 Department of Urology, Genitourinary Oncology Unit, Massachusetts General Hospital, Boston, Massachusetts; 4 Department of Surgery, Harvard Medical School, Boston, Massachusetts
Effect of thioredoxin interacting protein in retinal inflammation in high fat diet models
Osinakachukwu C. Mbata (1), Maha Coucha (2), Azza El-Remessy (2)
Introduction: Current evidence suggests that diet-induced obesity can contribute to both diabetic retinopathy (DR) in diabetic patients and in non-diabetic patients with the components of the metabolic syndrome. While the link between diabetes and DR is well-established, little is known about the association between obesity and DR.
Objective: Investigate the mechanism of high fat diet (HFD) in retinal inflammation. We explored this relationship by measuring the expression of thioredoxin interacting protein (TXNIP) and inflammasome activation in isolated primary Muller cells, the main glial cells in the retina.
Methods: Isolated primary Muller cells from TXNIP knockout (TKO) and wild type (WT), were cultured and subsequently exposed to either palmitate or hypoxia (1%) oxygen. Cells in “Pal” groups were stimulated with PAL-BSA (400μM), while cells in the control group were stimulated with BSA concurrently. Cells in the hypoxia group were stimulated in (1%) oxygen while control group remained in normoxic conditions. NLRP3-inflammasome activation was evaluated with ELISA and western blot for the following: NLRP3, Caspase-1, IL-1 β, and IL-18.
Results: Palmitate significantly upregulated NLRP3 expression in PMC isolated from WT mice, which was associated with an increase in IL1B. Knocking out TXNIP nullified the effect of palmitate on inducing NLRP3-inflammasome activation. Interestingly, similar findings were obtained with our hypoxic model. We found that exposing Muller cells to hypoxia led to an elevation in IL1B expression in cells isolated from WT mice but has no effect on TKO cells.
Conclusion: This study further elucidates the mechanism of the metabolic syndrome, namely obesity, on DR. Additionally, given that glycemic control has a threshold benefit in the management of DR, this study may begin to open up alternate therapeutic routes for the management and/or delay of DR.
1 Medical Scholars Program, Augusta University/University of Georgia Medical Partnership, Athens, Georgia; 2 University of Georgia, College of Pharmacy, Athens, Georgia
Friedreich’s Ataxia and mitochondrial training
Max Green (1), Nicole McGarrell (2), Caio Moraes (2), Robbi Van Schoick (2), Kevin McCully (2)
Purpose: The aim of this study was to examine exercise training adaptations in skeletal muscle of a person with Friedreich’s Ataxia (FRDA). Friedreich’s Ataxia is a congenital, autosomal recessive disease that results from a mutation in the gene for a mitochondrial protein known as Frataxin.
Methods: A case study was done on a 36-year-old female with FRDA. Four weeks of endurance training was performed using twitch electrical stimulation of the non-dominant forearm. Stimulation frequency was increased in stages from 2Hz to 4Hz to 6 Hz. Training was 30 minutes per day, 3 times per week. Before and after training muscle mitochondrial capacity was measured using near infrared spectroscopy. Muscle specific endurance was measured using twitch stimulations and an accelerometer on the muscle.
Results: Training sessions started with 4,200 contractions and progressed to 9,420 contractions. Muscle-specific endurance percentage increased after training (pre-training to 83.3% at 2 Hz, 56.2% at 4Hz and post-training 97.1% at 2 Hz and 73.3% at 4Hz). Mitochondrial capacity measured as a rate constant was unchanged after training (pre = 0.95 min-1 compared to 0.99 min-1 post-training).
Conclusions: The participant with FRDA showed evidence of training adaptations as indicated by increases in training volume and muscle endurance. Mitochondrial capacity did not change, but additional training time and or training intensity might be needed. This study, along with our recently submitted paper characterizing endurance and mitochondrial capacity in people with FRDA, support the use of the mitochondrial test and the endurance test as outcome measures for clinical trials for people with FRDA.
1 Medical Scholars Program, Augusta University/University of Georgia Medical Partnership, Athens, Georgia; 2 Department of Kinesiology, University of Georgia, Athens, Georgia
Impact of structured interdisciplinary bedside rounding on quality outcomes and provider satisfaction at an acute care community hospital
Jessica Principe, MS (1), Linda Gilhuly, BSN, RN (2), Ashton Roberts, MHA (2), Seyi Odubote, MS (3), Jennifer Waller, PhD (3), James Principe, MD (2)
Fragmented "silo" work and communication breakdown have been cited as contributing factors to poor healthcare quality and root cause of over 60% reported sentinel events, respectively. Structured interdisciplinary bedside rounding (SIBR) is a process designed to streamline interprofessional collaboration via team-based patient-centered communication at the bedside. SIBR has been associated with positive outcomes so far, but further investigation is warranted to evaluate the transferability of benefits to community hospital settings. The purpose of this study was to evaluate the effects of SIBR on hospital quality outcomes and provider satisfaction at a 167-bed acute care community hospital.
Quality data was obtained from April 2015 – March 2016 for eight hospitalist physicians and stratified by %SIBR-participation. Provider satisfaction surveys were administered in June-July 2016 and stratified by %SIBR-participation and unit. ANCOVA and ANOVA were used to determine differences for unstandardized and standardized variables, respectively. Tukey-Kramer multiple comparison procedure was used to for post-hoc pairwise comparisons, and two-sample t-test was used to examine differences in survey responses based on unit.
Only one hospital variable, average daily charge, showed a significant trend between SIBR participation levels, however post-hoc pairwise analysis did not show differences. Non-physician provider surveys showed significant differences between high- vs. low-SIBR groups with regard to teamwork, collaboration, knowing the plan of care, obtaining information from the physician, and overall communication. We did not find an effect of SIBR on length of stay or in-hospital mortality as in previous studies. Small sample size, multiple SIBR-participation levels, and inconsistent application of SIBR may have limited our ability to detect these effects. Non-physician provider satisfaction findings for teamwork, collaboration and related communication variables are consistent with previous work in this area, and to our knowledge, this is the first report to include non-nurse team members in surveys related to interdisciplinary bedside rounding.
1 Medical Scholars Program, Augusta University/University of Georgia Medical Partnership, Athens, Georgia; 2 Tidelands Waccamaw Community Hospital, Murrells Inlet, South Carolina; 3 Department of Biostatistics and Epidemiology, Medical College of Georgia at Augusta University, Augusta, Georgia
Predictors of readmission for heart failure
Thomas Beckworth (1), Jonathan Murrow, MD (2,3)
Currently there are over 5 million Americans with Congestive Heart Failure and this number continues to rise. Nationally 30-day hospital readmission rates for heart failure (HF) are incredibly high with about 25% of Medicare patients readmitted by 30 days. The purpose of this study was to show that HF patients embody a unique demographic group amongst patients admitted to the internal medicine service at Athens Regional in regards to age, gender, race, insurance status, and zip code in order to identify patients at high risk of readmission before discharge.
We performed a chart review of ARMC’s medical records isolating patients with HF diagnosis codes during a 90-day period. We compared demographic variables to a cohort of patients with non-heart failure diagnosis codes during the same period. This created a demographic overview of HF patients, which was compared to patients that were readmitted within 30 days of discharge to determine if they were enriched for a particular demographic. 1,993 total cases were reviewed with 173 HF admissions, and 40 HF readmissions.
The HF readmission group was appreciably enriched for older age (avg. 71.4 years), African American race (30%), and Medicare and Medicaid insurance (85%). Interestingly, lack of insurance was highest in the non HF cohort and least in the readmission group (10.9% vs. 2.5%). Higher readmission rates were seen from zip codes with lower per capita income, suggesting additional need in lower income communities.
1 Medical Scholars Program, Augusta University/University of Georgia Medical Partnership, Athens, Georgia; 2 Department of Cardiology, Athens Regional Medical Center, Athens, Georgia; 3 Augusta University/University of Georgia Medical Partnership, Athens, Georgia