Medicine and Health Sciences Commons^™

Deletion Of Sa Β-Gal+ Cells Using Senolytics Improves Muscle Regeneration In Old Mice, Cory M. Dungan, Kevin A. Murach, Christopher J. Zdunek, Zuo Jian Tang, Georgia L. Vonlehmden, Camille R. Brightwell, Zachary Hettinger, Davis A. Englund, Zheng Liu, Christopher S. Fry, Antonio Filareto, Michael Franti, Charlotte A. Peterson

Physical Therapy Faculty Publications

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl₂ or PBS 7- or 28 days prior to euthanization. Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice …

Gait And Balance Changes With Investigational Peripheral Nerve Cell Therapy During Deep Brain Stimulation In People With Parkinson’S Disease, Geetanjali Gera, Zain Guduru, Tritia R. Yamasaki, Julie A. Gurwell, Monica Chau, Anna Krotinger, Frederick A. Schmitt, John T. Slevin, Greg A. Gerhardt, Craig G. Van Horne, Jorge E. Quintero

Physical Therapy Faculty Publications

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the …

Injury Rates In Major League Baseball During The 2020 Covid-19 Season, Brooks N. Platt, Timothy L. Uhl, Aaron D. Sciascia, Anthony J. Zacharias, Nicole G. Lemaster, Austin V. Stone

Physical Therapy Faculty Publications

Background: The 2020 Major League Baseball (MLB) season was drastically altered because of the COVID-19 pandemic. The changes included an extended layoff between March and July as well as a shortened preseason.

Purpose/Hypothesis: To determine the incidence and epidemiology of MLB injuries in the abbreviated 2020 season compared with prior seasons. We hypothesized that there was an increase in the overall injury rate in the 2020 season compared with the 2018-2019 seasons and that it equally affected all body regions.

Study Design: Descriptive epidemiology study.

Methods: The MLB transactions database was queried to find players who had been placed on …

Development, Implementation And Outcomes Of A Quality Assurance System For The Provision Of Continuous Renal Replacement Therapy In The Intensive Care Unit, Eloy F. Ruiz, Victor M. Ortiz-Soriano, Monica Talbott, Bryan A. Klein, Melissa L. Thompson Bastin, Kirby P. Mayer, Emily B. Price, Robert Dorfman, Brandi N. Adams, Lisa J. Fryman, Javier A. Neyra, The University Of Kentucky Crrt Quality Assurance Group

Physical Therapy Faculty Publications

Critically ill patients with requirement of continuous renal replacement therapy (CRRT) represent a growing intensive care unit (ICU) population. Optimal CRRT delivery demands continuous communication between stakeholders, iterative adjustment of therapy, and quality assurance systems. This Quality Improvement (QI) study reports the development, implementation and outcomes of a quality assurance system to support the provision of CRRT in the ICU. This study was carried out at the University of Kentucky Medical Center between September 2016 and June 2019. We implemented a quality assurance system using a step-wise approach based on the (a) assembly of a multidisciplinary team, (b) standardization of …

Acute Skeletal Muscle Wasting And Dysfunction Predict Physical Disability At Hospital Discharge In Patients With Critical Illness, Kirby P. Mayer, Melissa L. Thompson Bastin, Ashley A. Montgomery-Yates, Amy M. Pastva, Esther E. Dupont-Versteegden, Selina M. Parry, Peter E. Morris

Physical Therapy Faculty Publications

BACKGROUND: Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge.

METHODS: Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of …

Microglia Prevent Beta-Amyloid Plaque Formation In The Early Stage Of An Alzheimer's Disease Mouse Model With Suppression Of Glymphatic Clearance, Weixi Feng, Yanli Zhang, Ze Wang, Hanrong Xu, Ting Wu, Charles Marshall, Junying Gao, Ming Xiao

Physical Therapy Faculty Publications

BACKGROUND: Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer's disease (AD) are currently unknown.

METHODS: Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4^−/−) mice, and AQP4^−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein …

Cardiorespiratory Fitness Diminishes The Effects Of Age On White Matter Hyperintensity Volume, Nathan F. Johnson, Ahmed A. Bahrani, David K. Powell, Gregory A. Jicha, Brian T. Gold

Physical Therapy Faculty Publications

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain …

Correlations Of Calf Muscle Macrophage Content With Muscle Properties And Walking Performance In Peripheral Artery Disease, Kate Kosmac, Marta Gonzalez-Freire, Mary M. Mcdermott, Sarah H. White, R. Grace Walton, Robert L. Sufit, Lu Tian, Lingyu Li, Melina R. Kibbe, Michael H Criqui, Jack M. Guralnik, Tamar S. Polonsky, Christiaan Leeuwenburgh, Luigi Ferrucci, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background

Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Methods and Results

Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients …

A Quantitative Comparison Of Arm Activity Between Survivors Of Breast Cancer And Healthy Controls: Use Of Accelerometry, Mary Insana Fisher, Claire C. Davies, Timothy L. Uhl

Physical Therapy Faculty Publications

Purpose

Survivors of breast cancer (BC) on the non-dominant side have more persistent deficits than those with cancer on the dominant limb. What is not known is whether those with BC use their involved upper limbs more, less, or at the same level as women without BC. Accelerometer use offers a quantifiable method to measure activity levels of upper limbs. The purpose of this study was to quantify the activity levels of the non-dominant involved limb among survivors of BC and compare these values to their dominant limb, as well as the non-dominant limb of a control group.

Methods

Participants …

Safety, Feasibility, And Efficacy Of Early Rehabilitation In Patients Requiring Continuous Renal Replacement: A Quality Improvement Study, Kirby P. Mayer, Amanda R. Hornsby, Victor Ortiz Soriano, Timothy C. Lin, Jennifer T. Cunningham, Hanwen Yuan, Caroline E. Hauschild, Peter E. Morris, Javier A. Neyra

Physical Therapy Faculty Publications

Introduction: Early rehabilitation in critically ill patients is associated with improved outcomes. Recent research demonstrates that patients requiring continuous renal replacement therapy (CRRT) can safely engage in mobility. The purpose of this study was to assess safety and feasibility of early rehabilitation with focus on mobility in patients requiring CRRT.

Methods: Study design was a mixed methods analysis of a quality improvement protocol. The setting was an intensive care unit (ICU) at a tertiary medical center. Safety was prospectively recorded by incidence of major adverse events including dislodgement of CRRT catheter, accidental extubation, bleeding, and hemodynamic emergency; and minor adverse …

A Comprehensive Rehabilitation Program For Treating Lateral Elbow Tendinopathy, Joseph M. Day, Ann M. Lucado, Timothy L. Uhl

Physical Therapy Faculty Publications

Scapular muscle weakness in patients with lateral elbow tendinopathy is an identified impairment and is part of a multimodal rehabilitation approach. The published literature provides little information regarding specific rehabilitation guidelines that address both the proximal scapular muscle weakness and local elbow/ wrist dysfunctions common in patients with lateral elbow tendinopathy. The purpose of this clinical commentary is to describe a comprehensive rehabilitation strategy for individuals with lateral elbow tendinopathy. This program emphasizes a phased therapeutic strategy that addresses proximal and local dysfunction along the kinetic chain. This clinical protocol is currently being tested for efficacy as part of a …

Endothelial Function Is Associated With White Matter Microstructure And Executive Function In Older Adults, Nathan F. Johnson, Brian T. Gold, Christopher A. Brown, Emily F. Anggelis, Alison L. Bailey, Jody L. Clasey, David K. Powell

Physical Therapy Faculty Publications

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI …

Serve Volume: How Important Is It?, Natalie L. Myers, W. Ben Kibler, Timothy L. Uhl

Physical Therapy Faculty Publications

No abstract provided.

Development, Validation And Application Of A New Fornix Template For Studies Of Aging And Preclinical Alzheimer's Disease, Christopher A. Brown, Nathan F. Johnson, Amelia J. Anderson-Mooney, Gregory A. Jicha, Leslie M. Shaw, John Q. Trojanowski, Linda J. Van Eldik, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Physical Therapy Faculty Publications

We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimer's disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in …

Wearable Imu For Shoulder Injury Prevention In Overhead Sports, Samir A. Rawashdeh, Derek A. Rafeldt, Timothy L. Uhl

Physical Therapy Faculty Publications

Body-worn inertial sensors have enabled motion capture outside of the laboratory setting. In this work, an inertial measurement unit was attached to the upper arm to track and discriminate between shoulder motion gestures in order to help prevent shoulder over-use injuries in athletics through real-time preventative feedback. We present a detection and classification approach that can be used to count the number of times certain motion gestures occur. The application presented involves tracking baseball throws and volleyball serves, which are common overhead movements that can lead to shoulder and elbow overuse injuries. Eleven subjects are recruited to collect training, testing, …

Cellular And Morphological Alterations In The Vastus Lateralis Muscle As The Result Of Acl Injury And Reconstruction, Brian W. Noehren, Anders H. Andersen, Peter A. Hardy, Darren L. Johnson, Mary Lloyd Ireland, Katherine L. Thompson, Bruce Damon

Physical Therapy Faculty Publications

Background: Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation.

Methods: We performed diffusion tensor imaging-magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine …

Reliability Of 3-Dimensional Measures Of Single-Leg Cross Drop Landing Across 3 Different Institutions: Implications For Multicenter Biomechanical And Epidemiological Research On Acl Injury Prevention, Christopher A. Dicesare, Nathaniel A. Bates, Kim D. Barber Foss, Staci M. Thomas, Samuel C. Wordeman, Dai Sugimoto, Benjamin D. Roewer, Jennifer M. Medina Mckeon, Stephanie Di Stasi, Brian W. Noehren, Kevin R. Ford, Adam W. Kiefer, Timothy E. Hewett, Gregory D. Myer

Physical Therapy Faculty Publications

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach.

Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions.

Study Design: Controlled laboratory study.

Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 …

Residual Impact Of Previous Injury On Musculoskeletal Characteristics In Special Forces Operators, Jeffrey J. Parr, Nicholas C. Clark, John P. Abt, Julie Y. Kresta, Karen A. Keenan, Shawn F Kane, Scott M. Lephart

Physical Therapy Faculty Publications

Background: Musculoskeletal injuries are a significant burden to United States Army Special Operations Forces. The advanced tactical skill level and physical training required of Army Special Operators highlights the need to optimize musculoskeletal characteristics to reduce the likelihood of suffering a recurrent injury.

Purpose: To identify the residual impact of previous injury on musculoskeletal characteristics.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Isokinetic strength of the knee, shoulder, and back and flexibility of the shoulder and hamstrings were assessed as part of a comprehensive human performance protocol, and self-reported musculoskeletal injury history was obtained. Subjects were stratified based …