Project Title: Neuromusculoskeletal Response of Activity-Based Rehabilitation and IGF-1 after Severe-Contusion Spinal Cord Injury in Rats
Faculty Mentor: Joshua Yarrow
Student: Russell Wnek
Research Project Description:
Recent estimates by the National Spinal Cord Injury Statistical Center show the annual incidence of spinal cord injury (SCI) is approximately 54 cases per one million people in the US. With a population size of 328 million, there are estimated to be 17,730 new SCI cases each year, and 291,000 people are estimated to be currently living in the US with an SCI1. Despite developments made in understanding SCI pathology and improvements in rehabilitation post-SCI, suffering from such an injury is a devastating event that has tremendous consequences on muscle and bone, thus contributing to deficits in functional ability.
Atrophy of skeletal muscle and diminished muscle function are hallmarks of SCI that are adversely associated with functional ability and increased risk for several metabolic comorbidities2. In addition to muscular deficits, loss of bone mineral density (BMD) and negative changes to the microarchitecture of bone are observed in SCI which lead to an increase in the risk of fracture3. The recovery of SCI has been concentrated on mechanical reloading strategies to attenuate the decline in muscle and bone related to disuse; however, the musculoskeletal decline occurring post-SCI is distinct when compared to other disuse conditions. For example, these musculoskeletal deficits are exaggerated by a combination of factors such as reduced circulating IGF-1 and impaired IGF-1 signaling4, 5. Such factors are thought to contribute to a rapid decline in muscle and bone as evidenced by humans with motor-complete SCI displaying bone loss at a faster rate than that resulting from prolonged bed rest or space-flight4. Partially, this rapid bone loss is due to uncoupled bone turnover occurring acutely in humans and rodents after SCI. Interestingly, this uncoupling has not been observed in other disuse models which suggest factors beyond disuse worsen the musculoskeletal decline observed post-SCI6.
Some activity-based physical rehabilitation therapies centering around the improvement of locomotor function have shown promise in enhancing muscular recovery in people with an incomplete SCI7. However, after more severe SCI, humans and animal models exhibit only minimal muscular improvement and negligible recovery of functional ability in response to certain activity-based rehabilitation therapies8. Currently, there are no rehabilitative or pharmacologic strategies shown to effectively and simultaneously regenerate muscle, bone, and functional ability post-SCI. To address this, activity-based physical rehabilitation supplemented with adjuvant pharmacologic IGF-1 to hasten musculoskeletal recovery, promote neuroplasticity, and improve functional ability is proposed.
Activity-Based Rehabilitation: Bodyweight-supported treadmill training (TM) and passive Cycle training are two commonly used rehabilitation therapies in individuals with SCI, and both modalities have been recently studied in a severe SCI rodent model in Dr. Yarrow’s lab. The most recent and preliminary data suggest TM and Cycle training alone after SCI do not preserve muscle mass and only minimally preserve skeletal integrity in a rodent severe contusion SCI model; however, notable differences in skeletal outcomes between the two modalities were observed. For example, SCI rats that were Cycle trained displayed a 6% higher cortical bone thickness and 10-15% higher cancellous bone volume at the distal femur and proximal tibia when compared to rats with SCI alone. This finding suggests Cycle training provided some skeletal benefit. With TM trained SCI rodents exhibiting worsening cancellous bone outcomes when compared to those that were Cycle trained, and the potential for reloading modalities (such as TM) to inflict fractures in osteoporotic limbs, Cycle training, with and without IGF-1, will be used as the modality of choice.
IGF-1: IGF-1 is a growth factor that is essential for normal growth, development, and maintenance of physiological strength in the musculoskeletal system9. With IGF-1 receptors present on numerous tissues, including osteoblasts and myocytes, IGF-1 has direct action on muscle and bone. Several labs have noted a decrease in IGF-1 and IGF-1 receptors in individuals and rodents post-SCI10; therefore, it is hypothesized that impaired IGF-1 signaling may have a determinantal effect on the musculoskeletal system after such an injury. Additionally, IGF-1 is known to persevere muscle integrity during reloading exercise which provides rationale for utilizing activity-based rehabilitation therapy in conjunction with IGF-1 to promote musculoskeletal recover post-SCI.
- The National Spinal Cord Injury Statistical Center. http://www.spinalcord.uab.edu/show.asp?durki=21446 (Accessed on May 11, 2007).
- DiPiro, N. D., Holthaus, K. D., Morgan, P. J., Embry, A. E., Perry, L. A., Bowden, M. G., & Gregory, C. (2015). Lower extremity strength is correlated with walking function after incomplete SCI. Topics in Spinal Cord Injury Rehabilitation, 21(2), 133–139. https://doi.org/10.1310/ sci2102-133
- McCarthy, I. D., Bloomer, Z., Gall, A., Keen, R., & Ferguson-Pell, M. (2012). Changes in the structural and material properties of the tibia
- Qin W, Bauman WA, Cardozo C. Bone and muscle loss after spinal cord injury: Organ interactions. Ann N Y Acad Sci. 2010;1211:66-84
- Bauman WA, Spungen AM, Flanagan S, Zhong YG, Alexander LR, Tsitouras PD. Blunted growth hormone response to intravenous arginine in subjects with a spinal cord injury. Horm Metab Res. 1994;26:152-156
- Yarrow JF, Conover CF, Beggs LA, Beck DT, Otzel DM, Balaez A, Combs SM, Miller JR, Ye F, Aguirre JI, Neuville KG, Williams AA, Conrad BP, Gregory CM, Wronski TJ, Bose PK, Borst SE. Testosterone dose dependently prevents bone and muscle loss in rodents after spinal cord injury. J Neurotrauma. 2014;31:834-845
- Harkema, S. J., Schmidt-Read, M., Lorenz, D. J., Edgerton, V. R., & Behrman, A. L. (2012). Balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using loco- motor training-based rehabilitation. Archives of Physical Medicine and Rehabilitation, 93(9), 1508–1517. https://doi.org/10.1016/j. apmr.2011.01.024
- Battistuzzo, C. R., Callister, R. J., Callister, R., & Galea, M. P. (2012). A sys- tematic review of exercise training to promote locomotor recovery in animal models of spinal cord injury. Journal of Neurotrauma, 29(8), 1600–1613. https://doi.org/10.1089/neu.2011.2199
- Bikle, D. D., Tahimic, C., Chang, W., Wang, Y., Philippou, A., & Barton, E. R. (2015). Role of IGF-I signaling in muscle bone interactions. Bone, 80, 79–88. https://doi.org/10.1016/j.bone.2015.04.036
- Tsitouras PD, Zhong YG, Spungen AM, Bauman WA. Serum testosterone and growth hormone/insulin-like growth factor-i in adults with spinal cord injury. Horm Metab Res. 1995;27:287-29
Project Title: Potential stress reduction methods influencing the prevention of psychiatric disorders and addictive behaviors in Florida medical students
Faculty Mentor: Lisa Merlo-Greene
Student: Kathryn Thompson
Research Project Description:
Medical students are under some of the highest stress conditions as they prepare to become physicians. As the concept of burnout has moved to the forefront of conversation in the American workforce, it is clear that medical students, resident physicians, and physicians are experiencing burnout on a larger scale compared to other trainees and professionals in other professions.1 As symptoms of burnout progress, medical students may begin to struggle with psychiatric disorders and substance abuse, especially depression, anxiety, and alcohol dependence.2-3 As these illnesses continue to develop with the stressors of medical school continuing to be piled on, there is an increased probability of leaving medical school altogether and no longer pursuing a career as a physician, and more importantly, an increased probability of developing suicidal thoughts.4 Not only is it disturbing that many physicians-in-training are suffering deleterious effects on their own well-being due to the inability to bear the burden of medical school stressors, but one must consider the consequent effects on patient safety and care. There is a noted decrease in empathy for patients and their situations, as well as decreased desire to serve patient populations most in need among medical students struggling with burnout.5 Additionally, with physicians already being overwhelmed with patient volume, losing medical students in their training will lead to a more severe physician shortage and potentially less quality healthcare since physicians can only spend a limited amount of time with patients in order to see the largest quantity of patients. The negative ramifications of burnout extend beyond the negative personal health effects into medical student professionalism and patient care.
Medical schools are beginning to hear the call for help to integrate medical student well-being into curriculum and promoting wellness initiatives that encourage students to find ways to reduce stress. When students realize that their medical school has wellness initiatives that cater to their wellness needs, the students may start to see a decline in their typical stressors.6 Some studies have been conducted targeting specific potential stress reducers including religion/spirituality, meditation practices, and regular exercise. Regular reliability on a student’s respected religion, few-week long meditation programs that aim to make meditation a regular habit, and regular exercise, especially group exercise, have all been found to lower burnout and decrease the usual stress medical students experience.7-10 There are countless other stress reducing techniques that have yet to be studied including the effects of adequate sleep; healthy eating; humanities-related outlets like writing, journaling, listening to music and reading; and cooking just to name a few. Understanding which wellness initiatives, resources, and support systems are the most effective in reducing stress for their medical students could greatly decrease the level of burnout, and potentially lower rates of psychiatric disorders and substance abuse.
We hypothesize that the use of more stress reduction methods is linked to decreased psychiatric disorder diagnoses in medical school, decreased exacerbations of pre-existing psychiatric disorders, and/or decreased substance abuse. The survey data explored a wide range of stress reduction methods, and it is likely that the more the students engaged in these behaviors, the more likely they were aware they needed these tools to succeed and maintain mental wellness. Likewise, these students would have remained mentally healthier compared to their peers who may not have developed stress reduction coping mechanisms. Additionally, we hypothesize that the more social support the students have during medical school, the less likely they will develop psychiatric disorders and/or dependence on substances to cope with the stressors of medical school. With extra support from family, friends, peers, and/or doctors, students would likely be more encouraged to push through and may even be encouraged by their support system to engaged in stress reduction behaviors that could maintain their mental wellness.
The main objective is to identify whether the greater use of stress reduction methods (i.e. healthy, moderate food consumption; adequate sleep as defined as at least 7-8 hours/night; regular exercise; etc.) as determined by number of methods used and frequency of use leads to decreased psychiatric disorder diagnoses in medical school, decreased exacerbations of pre-existing psychiatric disorders, and/or decreased substance abuse based on individual student responses to the “Florida Medical Student Wellness Survey.” Furthermore, the other aim of the project is to identify whether the greater number of social support factions relied upon during the six months prior to completing the survey also leads to decreased psychiatric disorder diagnoses in medical school, decreased exacerbations of pre-existing psychiatric disorders, and/or decreased substance abuse.
- Dyrbye, Liselotte N. MD, MHPE; West, Colin P. MD, PhD; Satele, Daniel; Boone, Sonja MD; Tan, Litjen MS, PhD; Sloan, Jeff PhD; Shanafelt, Tait D. MD Burnout Among U.S. Medical Students, Residents, and Early Career Physicians Relative to the General U.S. Population, Academic Medicine: March 2014 – Volume 89 – Issue 3 – p 443-451.
- Dyrbye, Liselotte N. MD; Thomas, Matthew R. MD; Shanafelt, Tait D. MD Systematic Review of Depression, Anxiety, and Other Indicators of Psychological Distress Among U.S. and Canadian Medical Students, Academic Medicine: April 2006 – Volume 81 – Issue 4 – p 354-373.
- Merlo, Lisa J., Curran, John S., Watson, Robert (2017). Gender differences in substance use and psychiatric distress among medical students: A comprehensive statewide evaluation, Substance Abuse, 38:4, 401-406
- Dyrbye, L. N., Harper, W., Durning, S. J., Moutier, C., Thomas, M. R., Massie, F. S., Eacker, A., Power, D. V., Szydlo, D. W., Sloan, J. A., & Shanafelt, T. D. (2011). Patterns of distress in US medical students. Medical teacher, 33(10), 834-839.
- Dyrbye, Liselotte N. MD, MHPE; Shanafelt, Tait D. MD Commentary: Medical Student Distress: A Call to Action, Academic Medicine: July 2011 – Volume 86 – Issue 7 – p 801-803.
- Real, F.J., Zackoff, M.W., Davidson, M.A. et al. Medical Student Distress and the Impact of a School-Sponsored Wellness Initiative. Med.Sci.Educ. 25, 397–406 (2015).
- Ghodasara, Sweta L., MD; Davidson, Mario A., PhD; Reich, Michael S., MD; Savoie, Corliss V., MD; Rodgers, Scott M., MD Assessing Student Mental Health at the Vanderbilt University School of Medicine, Academic Medicine: January 2011 – Volume 86 – Issue 1 – p 116-121.
- Shapiro, S.L., Schwartz, G.E. & Bonner, G. Effects of Mindfulness-Based Stress Reduction on Medical and Premedical Students. J Behav Med 21, 581–599 (1998).
- APA Dyrbye, Liselotte N. MD, MHPE; Satele, Daniel; Shanafelt, Tait D. MD Healthy Exercise Habits Are Associated With Lower Risk of Burnout and Higher Quality of Life Among U.S. Medical Students, Academic Medicine: July 2017 – Volume 92 – Issue 7 – p 1006-1011.
- Yorks DM, Frothingham CA, Schuenke MD. Effects of Group Fitness Classes on Stress and Quality of Life of Medical Students. The Journal of the American Osteopathic Association. 2017 Nov;117(11):e17-e25.