Master of Science, The Ohio State University, 2021, Kinesiology

Community-based behavioral and exercise interventions with in-person delivery models were challenged to find a new mode of delivery during the COVID-19 pandemic when access to in-person activities were compromised. These interventions are an essential part of chronic disease patients' self-management and health promotion efforts. One particularly prevalent chronic disease, knee osteoarthritis (knee OA), is the leading cause of functional decline in older adults and finding a safe way to deliver the intervention during the COVID-19 pandemic provided an opportunity to explore the feasibility, enablers, and barriers to virtual intervention delivery in this population. Access to community-based intervention settings for patients with knee OA remain limited even though it is well known that exercise combined with weight loss via dietary changes can provide clinically significant improvements to a patient's overall quality of life (QOL). While these meaningful results are well established, further investigation into the delivery of these interventions through online platforms and understanding the patients' perspective is still needed. By qualitatively capturing the experiences from patients who participated in the Collaborative Lifestyle Intervention Program for Knee Osteoarthritis Patients (CLIP-OA), further understanding can be explored about the feasibility and efficacy of this program to be delivered virtually via a video conferencing platform, such as Zoom, versus the established utility of in-person delivery. An especially important outcome to understand is the intervention's ability to educate patients in the application of knowledge and skills from the program and gather information about the patient's confidence to independently maintain the exercise and dietary behavior changes following cessation of the active intervention contacts. As, the pandemic disruption forced both a pause in in-person research activities and subsequent shift to alternate patient (open full item for complete abstract)

Committee: Dr. Sue Sutherland (Committee Member); Dr. Brian Focht (Advisor) Subjects: Behavioral Sciences; Health; Kinesiology

Master of Arts, The Ohio State University, 2006, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Arts, The Ohio State University, 2008, Graduate School

Committee: Not Provided (Other) Subjects:

Doctor of Philosophy, The Ohio State University, 2022, Kinesiology

Knee osteoarthritis (OA) progression represents a leading cause of mobility disability for older adults in the U.S. Being overweight or obese is a primary modifiable risk factor. It is recognized that lifestyle intervention represents an integral component of disease management efforts. However, following primary intervention, significant weight regain and behavioral recidivism is common. The overarching purpose of this dissertation was to explore the temporal relationships between key social cognitive determinants of lifestyle behavior and determine the feasibility and preliminary efficacy of virtually- delivered extended care contacts for improving weight loss and behavioral maintenance. Study I: Dynamics of Self-Efficacy, Goal Commitment, and Self-Regulation was a mediation analysis of extant data from the 18-month, Collaborative Lifestyle Intervention Program in knee OA patients (CLIP-OA) trial (M [SD] age = 65.4 [7.3]; M [SD] BMI = 35.1 [6.5] kg/m2). Self-efficacy (SE), goal commitment (GC), and self-regulation (SR) for PA were measured at 6, 12, and 18-month follow-up. Path analysis using bias- corrected bootstrapped 95% confidence intervals (CI) revealed the effect of 6-month SE on 18-month SR was partially mediated by level of GC at 12 months (β = 0.053, 95% CI = 0.028, 0.085), controlling for age, explaining 32.4% of the total effect. Study I provides evidence supporting hypothesized temporal relationships among key determinants of PA adoption and adherence in overweight and obese knee OA patients. Study II: The CLIP-OA Expansion Pilot Trial was a 6-month, two-arm, randomized, controlled pilot trial examining two schedules of virtually-delivered, group- mediated cognitive behavioral (GMCB) extended care contacts in a subsample of participants from CLIP-OA (n = 32; M [SD] age = 66.2 [6.1]). Upon completing 18 months of CLIP-OA, participants were allocated to receive either traditional (i.e., monthly; TRAD; n = 16), or 2, 3-week clusters of contacts (CL (open full item for complete abstract)

Committee: Brian Focht (Advisor); Carla Miller (Committee Member); Jeff Volek (Committee Member); Jerome D'Agostino (Committee Member) Subjects: Aging; Behavioral Sciences; Cognitive Psychology; Experiments; Health Sciences; Kinesiology; Social Psychology

Master of Science, The Ohio State University, 2022, Dentistry

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative bone disease that has been observed more in women than men. However, the causes of TMJ OA are multifactorial in nature and its diagnostic criteria are highly controversial. Recently, researchers have suggested using cone beam computed tomography (CBCT) to diagnose TMJ OA by counting imaging characteristics of mandibular condyle. The objective of this study was to examine whether bone mineral density (BMD) distribution in the TMJ condyle and mandibular facial morphology are associated with TMJ OA using patients' CBCT images. Methods: CBCT images of 35 adult patients (16 male and 19 female between 20 and 50 years old were retrospectively examined. Experienced clinicians including a dental radiologist determined TMJ OA counts. Right and left mandibular condyles were digitally cropped from CBCT images. A histogram of gray level that is proportional to BMD was obtained for each TMJ condyle. Mean, standard deviation (SD), fifth percentile low and high values (Low5 and High5) of the gray level histogram were determined. The CBCT based cephalometric images were used to measure the mandibular morphology. Results: Female group had significantly higher values of TMJ OA counts, mean and SD at the right mandibular condyle, High5 at both sides, and all gray value parameters for total (right + left) compared to male group (p<0.05). TMJ OA counts showed negative correlation with volume (p=0.005) and mean, Low5, High5. Specifically, antero-lateral (AL) region TMJ OA count showed significant interaction with gray value parameters (p<0.05). Conclusion: Female has more TMJ OA changes in mandibular condyle compared to male and BMD distribution confirmed its trend with significant positive correlations of gray value parameters. CBCT based gray value parameters of the condyles may provide useful information in patients for TMJ OA risk assessment especially when AL region of the condyle is captured.

Committee: Do-Gyoon Kim Dr (Advisor); Toru Deguchi Dr (Committee Member); Lisa Knobloch Dr (Committee Member); Sonya Kalim Dr (Committee Member); Hany Emam Dr (Committee Member) Subjects: Dentistry

PHD, Kent State University, 2021, College of Arts and Sciences / School of Biomedical Sciences

Osteoarthritis (OA) is a degenerative disease of articular cartilage that causes cartilage degradation, osteophyte formation, synovial inflammation, angiogenesis, and subchondral bone alteration. OA causes chronic disability in older people. Various factors are associated with its pathogenesis, including aging, obesity, joint instability, and joint inflammation. In healthy conditions, cartilage remodeling involves balanced interactions of synthesis and degradation to achieve homeostasis of the extracellular matrix (ECM) However, in OA this process becomes unbalanced, leading to pathologic changes in the affected joint. OA is also a highly prevalent rheumatic musculoskeletal disorder, that affected 303 million people globally in 2017. In the U.S. only, OA affects more than 32.5 million adults and is estimated to affect approximately 70 million more (i.e., 25% of the U.S. population) by 2030. Multiple OA factors might lead to stimulate the chondrocytes in the articular cartilage to produce the proteolytic enzymes which include matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) which work together to degrade joint articular cartilage leading to osteophyte formation and stiffening of joints. So far, there are no medications that can treat OA and all medicines such as analgesics, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) are used to reduce pain and inflammation. Trafficking protein particle complex subunit 9 (TRAPPC9) is a protein subunit part of the Transport Protein Particle II (TRAPPII), a highly conserved trafficking pathway from yeast to human. Not only TRAPPC9 is implicated in protein trafficking, but it has been also reported that TRAPPC9 regulates/potentiates multiple cellular activities such as prefiltration, differentiation, and function for several cell types through NF-kB mediation. To emphasize the relationship between TRAPPC9 and NF-kB, a study showed that TRAPPC9 physica (open full item for complete abstract)

Committee: Fayes Safadi Ph.D. (Advisor); Moses O. Oyewumi Ph.D. (Committee Member); Min-Ho Kim Ph.D. (Committee Member); Soumitra Basu Ph.D. (Committee Member); Mohammad Ansari Ph.D. (Committee Member) Subjects: Biology; Biomedical Research

Master of Science, University of Toledo, 2020, Mechanical Engineering

Osteoarthritis is one of the oldest recorded diseases that can impair movement and cause pain—affecting over half of the elderly community, osteoarthritis of the acromioclavicular joint is one of the most common sources of shoulder pain due to its ability to break down tissues within a joint due to repeated mechanical loadings. These loading repetitions eventually begin to form osteophytes at the articulating surfaces of the joint effectively increasing the stress at the joint and decreasing the spacing. Due to this decrease of space, the clinical physical examinations done involve moving the arm into positions that decrease the space further causing acute pain at the joint. One of the current standard clinical physical examination tests is the Cross Body Adduction test which has been shown to close the joint spacing a significant enough amount to cause irritation and signal the presence of osteoarthritis. However, a new test involving placing the hand behind the back, called the Reverse Shoulder Internal Rotation Test—also referred to as the Hand Behind the Back test—has been proposed after it was observed clinically to provide a more accurate osteoarthritis diagnosis than the Cross Body Adduction test for some patients. Through this work, both the Cross Body Adduction and Hand Behind the Back tests were modeled in order to determine if there is merit for the Hand Behind the Back test to be used as a diagnostic tool for clinicians. Both tests were modeled using the Zygote Solid 3D 50th Percentile Male Human Anatomy model (ZYGOTE, American Fork, UT) for the bone 3D models and MSC.ADAMS (MSC Software, Newport Beach, CA) to compile and run the simulations. Within MSC.ADAMS the bones were given compact bone material properties and were outfitted with joints, single-component forces for muscles, springs for ligaments, and normal to the rib's tangent springs to simulate the scapulothoracic articulation. Once the models were completed, the simulations were ran and it w (open full item for complete abstract)

Committee: Mohamed Samir Hefzy (Committee Chair); Brian Trease (Committee Member); Abdulazim Mustapha (Committee Member); Adam Schroeder (Committee Member) Subjects: Biomechanics; Engineering; Mechanical Engineering

PHD, Kent State University, 2020, College of Arts and Sciences / School of Biomedical Sciences

Osteoarthritis (OA) is one of the leading causes of disability and is caused by a combination of mechanical and biochemical factors. Accumulating evidence suggests that inflammation has a key role in the pathogenesis of OA, and nitric oxide (NO) is considered as one of the major inflammatory mediators in OA that drives many pathological changes during the development and progression of OA. Excessive production of NO in chondrocyte promotes cartilage destruction and cellular injury, and its synthesis in chondrocytes is catalyzed by inducible nitric oxide synthase (iNOS), which is thereby an attractive therapeutic target for the treatment of OA. A number of direct and indirect iNOS inhibitors, bioactive compounds, and plant-derived small molecules have been shown to exhibit a chondroprotective effect by suppressing the expression of iNOS. Currently, there is no effective disease-modifying drug available for OA. Small molecules have proved to be powerful tools for modulating important molecular pathways in development and disease. Our preliminary screening of selected small molecules led us to select imperatorin (IMP) and peretinoin (PRT), which exhibit anti-inflammatory properties; however, their effect in chondrocytes is unknown. IMP is a plant-derived compound, while PRT is an acyclic retinoid and is currently in clinical trials for its efficacy to treat hepato-carcinoma. We found that IMP, as well as PRT, inhibited IL-1β induced expression of iNOS and production of NO in primary human OA chondrocytes by modulating the activation of mitogen-activated protein kinase (MAPK) pathway. Additionally, PRT inhibited matrix degradation by suppressing the expression of matrix metalloproteinase-13 (MMP-13). The work described in this dissertation demonstrates that PRT inhibits the expression of iNOS and production of NO in primary human OA chondrocytes and cartilage explants, identifies the mechanism, and shows OA suppressive effects in a mouse OA model.

Committee: Tariq Haqqi (Advisor); Fayez Safadi (Committee Member); Moses Oyewumi (Committee Member); Mohammad Ansari (Committee Member); Christine Crish (Committee Member) Subjects: Biomedical Research

Master of Science (MS), Wright State University, 2020, Anatomy

Knee osteoarthritis (KOA), is globally prevalent source of disability for the elderly. This degenerative malady progresses with age and has no cure. It manifests in gait changes and affects overall quality of life. Exercise therapy has been shown to improve knee joint range of motion, stiffness and pain due to KOA. This improvement is due in part to the direct relationship between muscle strength and joint stability. The purpose of this study is to examine how a passive range of motion (ROM) exercises and stretching regimens affect gait-alterations and associated pain from KOA experienced during walking. Nine KOA subjects were recruited from a local orthopedic clinic and the Fel's longitudinal study, with a final sample size of 7 subjects completing the trial. Subjects performed self-paced walking trials before and after a 4-week long, bi-weekly set of passive ROM and stretching exercises. A trained pre-physical therapy student administered the therapy. Data necessary to assess gait before and after the intervention was acquired via standard gait analysis. Participants rated their pain before the intervention, at the fifth trial and after the intervention ended. Subjects experienced significant changes in walking speed, stride-length, cadence, peak knee flexion in stance, peak knee flexion in swing and knee flexion/extension (KFE) ROM in swing. Pain did not significantly decrease, remaining largely unchanged. These data supported our hypothesis that a combination of passive ROM and stretching would result in increased ROM and improved patient gait. Our hypothesis that pain would be significantly decreased was not supported. To improve effectiveness of rehabilitation, further research is needed to elucidate the effects of exercise therapy on osteoarthritis-based pain during ambulation.

Committee: Andrew W. Froehle Ph.D. (Advisor); Drew Pringle Ed.D., FACSM (Committee Member); Kathrin Engisch Ph.D. (Committee Member) Subjects: Anatomy and Physiology

Doctor of Philosophy, The Ohio State University, 2019, Biomedical Engineering

An anterior cruciate ligament (ACL) injury is a traumatic event that can lead to long term disability and greater risk of radiographically diagnosed osteoarthritis (OA). While ACL reconstruction (ACLR) can restore anterior laxity to acceptable levels, dynamic instability can persist. Analysis of gait and other sport specific tasks show persistent changes in lower limb mechanics that not only affect second injury risk, but may be a primary factor in early onset OA. A definitive mechanistic link has yet to be established between ACL injury, ACLR and OA, but current evidence strongly indicates that OA development is related to the changes in tibiofemoral kinematics that are present after injury and ACLR. Therefore, the aims of this dissertation were to: 1) Determine the effects of ACL injury and ACLR on lower limb biomechanics during sport specific tasks, and 2) Determine the effects of ACL injury and ACLR on subject specific model predicted ACL strain and cartilage contact patterns. The hypothesis tested was that lower limb biomechanics in those with ACLR would be significantly altered compared to their uninvolved limb and to uninjured controls. In addition, it was hypothesized that the models of ACLR subjects would predict larger ligament strains compared to the uninjured controls, and demonstrate altered cartilage contact patterns. To test these hypotheses, patients with ACLR were recruited for these studies. First, lower limb biomechanics during a single leg hop were examined to determine correlations with patient reported function at the return to sport (RTS) time point. In addition, patients with ACLR were also examined at longer follow-up times to determine how their peak kinetics and kinematics differed from their uninvolved limbs and uninjured controls during gait and a drop vertical jump (DVJ). The latter cohort of subjects underwent identical protocols to generate subject specific finite element (FE) models. These models were based on their magnetic re (open full item for complete abstract)

Committee: Alan Litsky MD, ScD (Advisor); Timothy Hewett PhD (Committee Member); Carmen Quatman MD, PhD (Committee Member); Matthew Reilly PhD (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Sports Medicine

Doctor of Philosophy, The Ohio State University, 2018, Comparative and Veterinary Medicine

Osteoarthritis (OA) is a progressive disease associated with cartilage injury and is the most common form of arthritis, affecting millions of people worldwide. Most common cartilage healing and treatments have unsatisfactory outcomes due to the inherently limited repair capability of cartilage. The goal here was to produce a sConstruct from decellularized synovial-derived extracellular matrix (sECM) seeded with synovial-derived mesenchymal stem cells (sMSCs) that could house normal or engineered sMSC with little immune reaction while improving cartilage healing. The first part of this work investigates the sMSC migration, differentiation, and distribution into the sECMs as determined by CD90, viability, histologic morphology, expression of GFP, BMP-2, hyaluronic acid (HA), and proteoglycan (PG). At day 14, sMSCs were viable, had multiplied 2.5-fold in the sECMs, had a significant decrease in CD90 expression and significant increases in HA and PG expression. Seeding with BMP-2-sMSCs enhanced the expression of BMP-2, and increased soluble HA and PG. These results indicate sMSC produce anabolic agents and differentiate in the sECM. The second portion of the thesis has two parts; 1) an in vitro model where the sConstructs were co-cultured with chondrocytes, and 2) in vivo, placing sConstructs adjacent to a cartilage lesion in a rat knee. The in vitro study showed increased chondrocyte proliferation, viability, and Col II production, greatest in BMP-2-sConstructs. Chondrocyte co-cultures increased the sConstruct sMSC production of HA, PG, and BMP-2 in a positive feedback loop. 2) In the in vivo study, sECM alone, GFP- or BMP-2-sConstructs were implanted adjacent to clinically created full-thickness rat-knee cartilage lesions. At 5 weeks, the lesion area was resected and gross anatomy, adjacent articulate cartilage growth and subchondral bone repair were scored and peripheral, central and cartilage lesion measurements taken. For all scores and measurements, sConstruct im (open full item for complete abstract)

Committee: Alicia Bertone (Advisor) Subjects: Animal Sciences; Veterinary Services

Master of Science, The Ohio State University, 2018, Comparative and Veterinary Medicine

Objective: To investigate effects of hyaluronic acid (HA) or HA combined with chondroitin sulfate (CS) and N-acetyl-d-glucosamine (NAG) by use of a lipopolysaccharide (LPS) in vitro method. Sample: Monolayer cultures of synovial cells from 4 adult horses. Procedure: Synovial cell cultures were untreated or treated with HA alone or HA- CS-NAG for 24 hours, subsequently unchallenged or challenge-exposed with 2 LPS concentrations (20 and 50 ng/mL) for 2 hours, and retreated with HA or HA-CS-NAG for another 24 hours. Cellular morphology of cultures was evaluated at 0, 24 (before LPS), 26 (after LPS), and 50 (24 hours after end of LPS) hours. At 50 hours, cell number and viability and prostaglandin (PG) E2, interleukin (IL)-6, matrix metalloproteinase (MMP)3, and cyclooxygenase (COX)-2 production were measured. Results: LPS challenge exposure induced a significant loss of characteristic synovial cell morphology, decrease in cell viability, and increases in concentrations of PGE2, IL-6, MMP-3, and COX-2. Cells treated with HA or HA-CS-NAG had significantly better viability and morphology scores and lower concentrations of PGE2, MMP-3, IL-6, and COX-2 than untreated LPS challenge-exposed cells. Cells treated with HA had significantly better morphology scores at 50 hours than cells treated with HA-CS-NAG. Cells treated with HA-CS-NAG had significantly superior suppression of LPS-induced production of PGE2, IL-6, and MMP-3 than cells treated with HA alone. Conclusion and Clinical Relevance: HA and HA-CS-NAG protected synovial cells from the effects of LPS. Treatment with HA-CS-NAG had the greatest anti-inflammatory effect. These results supported the protective potential of HA and HA-CS-NAG treatments.

Committee: Alicia Bertone (Advisor); Matthew Brokken (Committee Member); Prosper Boyaka (Committee Member) Subjects: Veterinary Services

Master of Science, The Ohio State University, 2018, Allied Medicine

Background: Arthritis is a musculoskeletal condition, which results in joint pain, swelling, functional impairment, disability, and loss of quality of life. Inflammation plays a key role in the development and severity of arthritis and the Mediterranean diet has shown to improve inflammation and arthritis symptoms. There is a greater applicability for clinicians and patients to focus on dietary patterns instead of specific nutrients to make positive dietary changes to manage their condition. Objective/Hypothesis: To investigate the differences in adherence to the Mediterranean diet and diet quality between presence and type of arthritis and to determine the association between diet quality and presence of arthritis. Methods: Cross-sectional data from four cycles (2007-2014) of the National Health and Nutrition Examination Survey (NHANES) was utilized and weighted to produce a nationally representative sample. Arthritis information was extracted from the Medical Conditions file and recoded into relevant variables. Food group and nutrient data from the 24-hour recall was transformed to provide alternate Mediterranean Diet (aMED) scores and Healthy Eating Index 2015-2020 (HEI-2015) scores. Results: Individuals with arthritis (rheumatoid arthritis (RA) and osteoarthritis (OA)) had significantly worse adherence to the Mediterranean diet and diet quality. aMED scores were 3.43 ± 0.04 for individuals with arthritis and 3.54 ± 0.03 for individuals without arthritis (p=0.016). HEI-2015 scores were also lower in individuals with arthritis (51.42 ± 0.37) compared to without (53.48 ± 0.28) (p<0.001). There were no significant differences in aMED scores or HEI-2015 scores between RA and OA. There were also no associations between aMED scores or HEI-2015 scores and the presence of arthritis. Conclusions: Individuals diagnosed with arthritis can take steps to improve their diet quality as a possible route to reduce their arthritis symptoms. Further research on dietary patt (open full item for complete abstract)

Committee: Jessica Krok (Advisor); Christopher Taylor (Committee Member); Marcia Nahikian-Nelms (Committee Member); Latha Ganesan (Committee Member) Subjects: Aging; Nutrition

PHD, Kent State University, 2017, College of Arts and Sciences / School of Biomedical Sciences

Osteoarthritis (OA) is a degenerative form of arthritis leading to joint disability. It has been estimated that more than 15% of world's population have joint diseases, and more than 27 million Americans have OA. Furthermore, European Union has more than 39 million people with OA, and probably by 2020, these numbers will be doubled. Multiple factors induce OA leading to stimulate articular cartilage chondrocytes to produce the proteolytic enzymes these enzymes included matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) which work together to degrade joint articular cartilage leading to osteophyte formation and stiffening of joints. So far, there are no medications that can treat OA, and all medicines such as analgesics, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) are used to reduce the pain and inflammation. GPNMB also called Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) is a type I transmembrane glycoprotein expressed in multiple cell types and involved in multiple cell functions such as proliferation, differentiation, and apoptosis. Studies discovered the role of GPNMB in tumors, neurons, muscles, and bones while the role of GPNMB in cartilage is unknown. Our study aims to discover the role of GPNMB in cartilage homeostasis in post-traumatic OA. microRNA (miRNA) is a small non-coding RNA consisting of ~22 nucleotides which regulate gene expression through targeting the 3'UTR region of the target mRNA. miRNA accounts for 1-5% of the human genome and regulate at least 30% of protein-coding genes and are involved in cells functions regulation. In our study, we focused on the impact miRNA-150 on GPNMB in vivo and in vitro. The current study is composed of three hypothesizes. First, GPNMB has an anti-inflammatory role in osteoarthritis by reducing the catabolic genes such as MMP-3, MMP- 9, MMP-13, ADAMTS4, and interleukin-6 (IL-6). Second, GPNMB is negatively (open full item for complete abstract)

Committee: Fayez Safadi (Advisor); Inman, Denise (Committee Member); Kim, Min-Ho (Committee Member); Oyewumi, Moses (Committee Member); Fraizer, Gail (Committee Chair) Subjects: Biomedical Research; Immunology; Molecular Biology

Doctor of Philosophy, The Ohio State University, 1985, Graduate School

Committee: Not Provided (Other) Subjects: Statistics

Doctor of Philosophy, The Ohio State University, 2015, Comparative and Veterinary Medicine

Osteoarthritis (OA) of the knee is a major public health problem that primarily affects the elderly. Almost 10% of the U. S. population suffers from symptomatic knee OA by the age of 60. There are no approved interventions that ameliorate structural progression of this disorder. The increasing importance of imaging in animal models of osteoarthritis for diagnosis, prognostication, and follow-up is of paramount importance and plays a crucial role in increasing our understanding of the etiology of OA and in the development of new therapies. A primary aim of this study was to provide a comprehensive imaging analysis of the whole knee joint serially in a surgically induced in vivo canine model of OA. We elucidated that quantitative magnetic resonance imaging (MRI) markers demonstrated early changes in the cartilage of the knees that underwent anterior cruciate ligament transection (ACLT) relative to the control knee. This study provided evidence that T2 mapping and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are imaging markers relevant to the initiation and progression of OA. Conventional radiography knee assessment, the gold standard in OA diagnosis showed OA signs at a later stage of OA, lacking evidence of premature signs of OA. Serial in vivo imaging utilizing 2-deoxy-2-[fluorine-18] fluoro- D-glucose (18F-FDG) and sodium 18 F-fluoride (18F-NaF) Positron Emission Tomography /Computed Tomography (PET/CT) were performed to characterize knee metabolic and remodeling activity. PET was co-registered with MRI to allow us to improve the location of the regions of interest, otherwise unattainable with PET alone. This work demonstrated, providing imaging evidence, that 18F-FDG and 18F-NaF served an important role in detecting early OA metabolic and remodeling changes in the knee prior to the expression of gross changes. These in vivo changes, in addition to ex vivo micro-PET/CT using 18F-NaF and histomorphometry assessment provided a more valuable understanding o (open full item for complete abstract)

Committee: Michael Knopp (Advisor); Michael Tweedle (Committee Member); Thomas Rosol (Committee Member); David Flanigan (Committee Member) Subjects: Biomedical Research; Medical Imaging

Master of Science, University of Toledo, 2015, Exercise Science

Context: Symptomatic knee osteoarthritis (OA) affects 12.1% of adults over the age of 60 in the United States, making OA the leading cause of disability for older adults in the U.S. OA is a degenerative disease characterized by joint space narrowing, development of osteophytes, and articular cartilage degeneration. Symptoms associated with knee OA include pain, loss of motion, and decreased functional ability. These factors lead to disability, decreased quality of life, and a higher risk of comorbidities including obesity and cardiovascular disease. OA has been shown to also affect voluntary quadriceps strength and activation, further impairing function and quality of life. These neuromuscular alterations affecting the injured joint are referred to as central activation deficits (CAD). This affects the ability to activate motor neurons around the joint for recruitment during normal muscular contractions. This results in decreased muscle contraction capabilities and becomes a problem when these deficits persist and limit the ability to regain optimal muscle function. However, it is not fully understood how these deficits contribute to and worsen knee OA. Objective: To understand how knee OA influences quadriceps strength and central activation. Additionally, we sought to determine if a group-based exercise intervention could augment CAD in women with knee OA. Design: Pilot investigation with an embedded case series. Setting: Research laboratory. Methods: Baseline demographics were recorded on all participants. Baseline MVIC and CAR were measured using the burst superimposition technique. Baseline TMS measures (AMT, SICI, LICI, ICF) were calculated. Participants completed the 8-week therapeutic exercise intervention. Follow-up MVIC and CAR were recorded. Participants: Nine patients (age=57.11±5.28, height=1.71±0.06m, mass=90.52±22.58kg, BMI=30.81±6.69) completed baseline strength and CAD measures. Three patients (age=59.67±2.89, height=1.70±0.00m, mass= (open full item for complete abstract)

Committee: Luke Donovan (Committee Chair); Abbey Thomas (Committee Member); Michele Pye (Committee Member) Subjects: Health; Health Care; Health Sciences

Master of Science, University of Toledo, 2015, Exercise Science

Those who are affected by osteoarthritis (OA) of the knee have shown decreased levels of functional capacity and quality of living. This disability has been linked to decreased levels of strength and physical activity caused by pain or fatigue. Resistance training and increased levels of physical activity have shown to improve these deficits. However, an efficient way to treat a large number of patients by increasing physical activity levels has not yet been determined. Furthermore, it is unknown if a simple, body weight-based exercise program is capable of achieving similar gains as previously-developed, machine-based programs. This thesis examined the effects of a group-based, eight-week therapeutic exercise regimen on functional performance, self-reported outcomes and physical activity levels in elderly female patients with knee OA. The study design for this pilot project was that of an observational study with an embedded case series. Seven patients (mean age = 56.0±5.42) were included in the group exercise regimen. The exercise regimen was performed once a week and included body weight exercises, balancing, and walking. Self-reported outcomes and pain were measured via the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Numeric Pain Rating Scale (NPRS). Functional performance was measured by use of the chair stand test (CST), timed up and go test (TUG), stair climb test (SCT), and the six-minute walk test (6MW). Physical activity levels were measured by use of accelerometers and the UCLA activity scale. All measures were collected one week previous to the eight-week exercise regimen and one week following the exercise regimen. Overall, WOMAC (34.57±15.52 to 23.42±11.96) and NPRS (5.43±1.81 to 2.29±2.93) scores improved as a result of the exercise regimen. Also, the CST (10.21±1.07 reps to 12.00±1.61 reps), TUG (9.65±1.42s to 8.23±1.44s), SCT (13.03±0.70s to 11.6±1.07s) and 6MW (454.09±59.77m to 504.21±54.64m) functional (open full item for complete abstract)

Committee: Luke Donovan Dr. (Advisor); Michele Pye Dr. (Committee Member); Abbey Thomas Dr. (Committee Member) Subjects: Health; Health Sciences; Kinesiology; Medicine; Rehabilitation; Therapy

Master of Science, The Ohio State University, 2015, Comparative and Veterinary Medicine

Osteoarthritis (OA) is a common cause of debilitating lameness in dogs. Although osteoarthritis is classified as a non-inflammatory disease, low levels of inflammation are present in the joint and can affect the progression of the disease. Osteoarthritis is characterized by degradation and loss of articular cartilage, osteophyte formation, subchondral bone sclerosis and inflammation of the synovial membrane. As cartilage begins to breakdown, the ratio of naturally occurring inflammatory to anti-inflammatory cytokines becomes imbalanced causing increased breakdown of cartilage. A novel method for up regulation of anti-inflammatory cytokines from whole blood has been reported which produces an autologous protein solution (APS). Injection of APS has been shown to be an effective treatment of OA in horses and has greater anti-inflammatory proteins than platelet-rich plasma, another protein solution used for treatment of OA. The objective of the study was to prospectively evaluate the efficacy of an intra-articular injection of APS for treatment of OA in dogs using the Canine Brief Pain Inventory (CBPI) to score pain, Hudson visual analog scale (HVAS) to score lameness, and peak vertical force (PVF) to evaluate weight-bearing. Twenty client-owned dogs with a unilateral lameness attributable to OA of the elbow or stifle were enrolled and randomly assigned to a joint injection with APS or 0.9% saline solution. Owners and observers performed assessments blinded prior to injection, and at week 2 and 12 after injection. Radiographs of the affected joint were made prior to injection and at week 12. For dogs that received the APS injection, lameness scores (improved 25.6%; P<0.03), pain scores (improved 15%; P<0.05) and peak vertical force (increased 14.9%; (P<0.2) showed significant improvement at week 12 compared with pretreatment values. For control dogs, lameness scores, pain scores and peak vertical force at week 12 were not significantly different from pretrea (open full item for complete abstract)

Committee: Alicia Bertone (Advisor); Bianca Hettlich (Committee Member); Lisa Zekas (Committee Member) Subjects: Veterinary Services

Doctor of Philosophy, The Ohio State University, 2015, Mechanical Engineering

Over 50 million adults in the United States report doctor-diagnosed osteoarthritis (OA), which includes almost 50% of all people over the age of 65. There are no current treatments to stop the progression of OA; therefore, joint replacement is generally considered the final step to improve function and reduce pain in weight bearing joints. Increased varus-valgus laxity has been reported in participants with knee OA compared to controls, while passive stability is a major concern for orthopaedic surgeons during total knee arthroplasty (TKA). The purpose of this dissertation is to better understand the role of passive varus-valgus laxity on biomechanical, clinical and self-reported function in individuals with severe OA and following TKA. Chapter 1 provides background information on tibiofemoral OA and TKA, while outlining the impact of knee stability on disease progression and outcomes. Chapter 2 is a systematic review of the literature containing varus-valgus laxity measurements in patients with OA. This research unearthed consistent findings indicating increased varus-valgus laxity is a characteristic of knee joints with OA. Large variances exist in reported varus-valgus laxity and may be due to differences in measurement devices. The remaining chapters include experimental data collected before, during, and after TKA from study volunteers. Chapter 3 assessed passive varus-valgus laxity in 30 osteoarthritic knees and found greater laxity was significantly associated with more varus-valgus excursion during gait (R2=0.34, p=0.002). However, no relationship was observed between passive varus-valgus laxity and knee flexion strength, perceived instability, or any Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales. Chapter 4 investigated the relationship between passive varus-valgus laxity and active stability of the knee joint provided by muscle activation and co-contraction. This analysis utilized data from 22 knees and found no relationship be (open full item for complete abstract)

Committee: Ajit Chaudhari PhD (Advisor); Alan Litsky MD, ScD (Committee Member); Laura Schmitt PhD, PT (Committee Member); Robert Siston PhD (Committee Member) Subjects: Biomechanics; Mechanical Engineering; Surgery