The Shared Contributions Of The Capsule, Labrum, And Bone On The Suction Seal Of The Hip, Alexander J. Hoffer

Electronic Thesis and Dissertation Repository

The hip capsule, labrum, and bone contribute to hip stability. Abnormalities in these structures are associated with pain and microinstability. Previous studies have quantified the individual stabilizing roles of the capsule and labrum and have associated cam over-resection with decreased hip stability.

The first objective of this thesis was to identify the relative biomechanical contributions of the capsule, labrum, and bone to the hip suction seal, as a representation of hip stability. The second objective was to assess the effectiveness of a labral reconstruction in restoring the suction seal after a cam over-resection.

Ten human cadaveric hips were tested in …

Evaluation Of Conservative And Operative Treatments In Active Patients With Acromioclavicular (Ac) And Rotator Cuff (Rc) Injuries, Jesse Singh

Electronic Thesis and Dissertation Repository

Abstract

Introduction: Shoulder pain and disability, particularly acromioclavicular joint (ACJ) and rotator cuff (RC) injuries, are common in a physically active population. Determining operative or rehabilitative treatment plans involve multiple treatment choices influenced by the injury grade and treatment goals, such as return to sport. This thesis investigates the management of treatment for AC and RC injuries

Method: The first study is a scoping review that uses the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) to synthesize 32 studies involving athletes who have undergone conservative or operative treatment for their Rockwood grade III …

Pannexin3 In Exercise, Obesity, And Osteoarthritis, Brent Wakefield

Electronic Thesis and Dissertation Repository

Pannexin 3 (PANX3), is a glycoprotein that oligomerizes to form mechano-sensitive channels expressed in musculoskeletal tissues, and has been identified as a potential target for the treatment of obesity and osteoarthritis (OA). Obesity and OA are two of the most prevalent diseases worldwide, leading to disability and even death. These conditions are thought to originate from a complex interaction between genetics, aging, sex, and modifiable lifestyle factors, such as exercise. Investigating the interactions between genetic and exercise may provide a more comprehensive, context-specific understanding of gene function. This thesis aimed to understand the interactions between PANX3 and exercise interventions on …

A Review Of The Neural Basis Underlying The Acoustic Startle Response With A Focus On Recent Developments In Mammals, Alice Zheng, Susanne Schmid

Anatomy and Cell Biology Publications

The startle response consists of whole-body muscle contractions, eye-blink, accelerated heart rate, and freezing in response to a strong, sudden stimulus. It is evolutionarily preserved and can be observed in any animal that can perceive sensory signals, indicating the important protective function of startle. Startle response measurements and its alterations have become a valuable tool for exploring sensorimotor processes and sensory gating, especially in the context of pathologies of psychiatric disorders. The last reviews on the neural substrates underlying acoustic startle were published around 20 years ago. Advancements in methods and techniques have since allowed new insights into acoustic startle …

Plantar Flexor Dynamic Contractile Rates Are Not Dependent On Calcaneal Tendon Stiffness, Sohum Kulkarni

Electronic Thesis and Dissertation Repository

The ability to rapidly generate muscular torque and velocity is important in specialized activities and daily tasks of living. Tendon stiffness is one factor in the neuromuscular system that influences musculoskeletal torque transmission. Previous studies have reported weak-to-moderate correlations between tendon stiffness and rate of torque development (RTD). However, these correlations have been reported only for isometric contractions which may not be relevant to contractions involving joint rotation (i.e., dynamic). The purpose was to investigate the effect of calcaneal tendon stiffness on the dynamic rates of torque (RTD) and velocity (RVD) development in plantar flexor muscles. Young adult males (n=13) …

Spatiotemporally Dynamic Electric Fields For Brain Cancer Treatment: An In Vitro Investigation, Erin Iredale, Abdulla Elsaleh, Hu Xu, Paul Christiaans, Andrew Deweyert, John Ronald, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

Objective. The treatment of glioblastoma (GBM) using low intensity electric fields (∼1 V cm^-1) is being investigated using multiple implanted bioelectrodes, which was termed intratumoral modulation therapy (IMT). Previous IMT studies theoretically optimized treatment parameters to maximize coverage with rotating fields, which required experimental investigation. In this study, we employed computer simulations to generate spatiotemporally dynamic electric fields, designed and purpose-built an IMT device for in vitro experiments, and evaluated the human GBM cellular responses to these fields. Approach. After measuring the electrical conductivity of the in vitro culturing medium, we designed experiments to evaluate the …

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Novel 129xe Magnetic Resonance Imaging And Spectroscopy Measurements Of Pulmonary Gas-Exchange, Alexander M. Matheson

Electronic Thesis and Dissertation Repository

Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy.

In vivo Xenon-129 gas-exchange magnetic resonance imaging (¹²⁹Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized ¹²⁹Xe gas, it …

Vertebral Endplate Structural Defects: Measurement, Prevalence And Associated Factors, Aliyu Lawan

Electronic Thesis and Dissertation Repository

Objective: To synthesize current knowledge on the association of endplate structural defects (EPSD) with back pain (BP), improve EPSD measurement, and investigate EPSD prevalence, distribution, and association with age and body mass index (BMI).

Methods: In study 1, a systematic review was conducted on five databases for studies reporting on the association between EPSD and BP. Studies 2 and 3 used CTs and mCTs of 19 embalmed cadavers to examine the diagnostic accuracy of common EPSD assessment methods, and to develop and validate a novel method. Study 4 used the novel method on 200 adult males’ MRI to estimate EPSD …

Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are …

Characterizing Maternal Isolation-Induced Ultrasonic Vocalizations In A Gene-Environment Interaction Rat Model For Autism., Dorit Möhrle, Megan Yuen, Alice Zheng, Faraj L Haddad, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and …

Investigating Behavioral Phenotypes Related To Autism Spectrum Disorder In A Gene-Environment Interaction Model Of Cntnap2 Deficiency And Poly I:C Maternal Immune Activation, Faraj L Haddad, Cleusa De Oliveira, Susanne Schmid

Anatomy and Cell Biology Publications

Introduction: Autism Spectrum Disorder (ASD) has been associated with a wide variety of genetic and environmental risk factors in both human and preclinical studies. Together, findings support a gene-environment interaction hypothesis whereby different risk factors independently and synergistically impair neurodevelopment and lead to the core symptoms of ASD. To date, this hypothesis has not been commonly investigated in preclinical ASD models. Mutations in the Contactin-associated protein-like 2 (Cntnap2) gene and exposure to maternal immune activation (MIA) during pregnancy have both been linked to ASD in humans, and preclinical rodent models have shown that both MIA and Cntnap2 deficiency …

The Clinical Value Of Oculomotor Assessments Across The Continuum Of Concussion, Dillon Richards

Electronic Thesis and Dissertation Repository

Concussions are complex conditions that are difficult to manage medically. Variations in symptom presentation, intricate neurophysiological processes, and the availability of a variety of possible assessment tools may contribute to this complexity. Clinicians must use a broad approach, employing both subjective symptom assessment and objective assessments to confirm a diagnosis and/or monitor progression and recovery. Oculomotor function after concussion may be an important indicator of injury, given the interconnectedness of oculomotor function, vestibulo-ocular and visual systems, and even cognition. Oculomotor function may be assessed objectively or indirectly using patient-reported symptom checklists as part of subjective assessments. One way of objectively …

Hyperexcitable And Immature-Like Neuronal Activity In The Auditory Cortex Of Adult Rats Lacking The Language-Linked Cntnap2 Gene., Kaela E Scott, Rajkamalpreet S Mann, Ashley L Schormans, Susanne Schmid, Brian L Allman

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in …

Planning System For The Optimization Of Electric Field Delivery Using Implanted Electrodes For Brain Tumor Control, Erin Iredale, Brynn Voigt, Adam Rankin, Kyungho W Kim, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

BACKGROUND: The use of non-ionizing electric fields from low-intensity voltage sources (< 10 V) to control malignant tumor growth is showing increasing potential as a cancer treatment modality. A method of applying these low-intensity electric fields using multiple implanted electrodes within or adjacent to tumor volumes has been termed as intratumoral modulation therapy (IMT).

PURPOSE: This study explores advancements in the previously established IMT optimization algorithm, and the development of a custom treatment planning system for patient-specific IMT. The practicality of the treatment planning system is demonstrated by implementing the full optimization pipeline on a brain phantom with robotic electrode implantation, postoperative imaging, and treatment stimulation.

METHODS: The integrated planning pipeline in 3D Slicer begins with importing and segmenting patient magnetic resonance images (MRI) or computed tomography (CT) images. The segmentation process is manual, followed by a semi-automatic smoothing step that allows …

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

The Design And Evaluation Of A Subacromial Implant In Restoring Normal Glenohumeral Joint Stability In The Presence Of A Massive Irreparable Rotator Cuff Tear, Cole T. Fleet

Electronic Thesis and Dissertation Repository

Massive irreparable rotator cuff tears are a common cause of pain and disability. Several different treatment options are available for this pathology; however, these treatments have been associated with poor clinical outcomes when used to treat younger (<65 years), more active patients. The purpose of this thesis was to design and evaluate a subacromial implant in its ability to restore normal glenohumeral stability and range of motion. The implant was created as a modular device, which captured different implant thicknesses (5mm and 8mm) and constraints (high and low) within its design. In-vitro testing compared the ability of these implants to restore normal shoulder biomechanics. The results indicated the 5mm high constraint implant to be the most effective in restoring normal joint position. Furthermore, range of motion increased when the implant was paired with a tuberoplasty procedure. These results suggest this implant may be advantageous in treating younger patients.

Rapid Changes In Vascular Compliance Contribute To Cerebrovascular ​Adjustments During Vasovagal Syncope (Vvs), Aleena Sajid

Undergraduate Student Research Internships Conference

Background: The rapid reduction in arterial pressure (AP) during VVS is associated with a decline in diastolic cerebral blood velocity (CBV) and maintained systolic CBV. We tested the hypothesis that this response may represent increased cerebrovascular compliance (Ci) in the presence of rapid hypotension.

Methods: AP and CBV were recorded from 14 otherwise healthy patients (34 ± 11 years) at rest and during head-up tilt (80°, 5-28 min). Baseline, mid-tilt, and VVS were analyzed. Individual AP and CBV waveforms were input into a modified Windkessel model to calculate Ci.

Results: Upright posture resulted in a decrease in CBV (-9 ± …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

Automation Through Deep-Learning To Quantify Ventilation Defects In Lungs From High-Resolution Isotropic Hyperpolarized 129xe Magnetic Resonance Imaging, Tuneesh Kaur Ranota

Electronic Thesis and Dissertation Repository

Obstructive lung diseases are characterized by heterogenous ventilation. Hyperpolarized ¹²⁹Xe gas lung magnetic resonance imaging (MRI) can examine lung ventilation heterogeneity by acquiring high-resolution isotropic images. The current gold standard of semi-automated (SA) segmentation can be used to quantify non-isotropic ¹²⁹Xe lung images to generate ventilation defect percent (VDP), however, this method is not suitable for analysis of isotropic voxel ¹²⁹Xe images due to the large number of slices. Therefore, we used a fully automated deep learning-based (DL) lung algorithm to calculate VDP from isotropic images. SNR, SA and DL-based VDP were calculated, showing a strong positive …

Role Of The Epithelial-To-Mesenchymal Transition (Emt) On Circulating Tumor Cell (Ctc) And Metastasis Biology In Prostate Cancer, Jenna M. Kitz

Electronic Thesis and Dissertation Repository

Prostate cancer is the second leading cause of cancer-related deaths in American men. Most of these deaths occur as the result of metastasis, which is associated with an epithelial-to-mesenchymal transition (EMT). EMT leads to greater migratory/invasive capacity and resistance to therapy. During metastasis and associated EMT, cancer cells shed from the primary tumor and disseminate throughout the body as circulating tumor cells (CTCs) in the bloodstream. CTCs have been correlated with increased metastatic disease, reduced survival, and therapy response/resistance. Assessing CTCs presents an opportunity to study cancer progression/treatment effectiveness from a blood test. However, outstanding questions regarding CTCs and EMT …

Connexin 43 Contributes To Phenotypic Variability Of The Mouse Skull, Elizabeth Jewlal

Electronic Thesis and Dissertation Repository

The purpose of this study was to determine whether connexin 43 (Cx43) contributes to craniofacial phenotypic variability. Skull shape and variation were compared within and among two heterozygous mutant mouse models (G60S/+ and I130T/+) that exhibit different levels of Cx43 channel function when compared to their wildtype counterparts (~80% and ~50% reduction in function, respectively). Results indicated mutants have significant differences in skull shape compared to wildtype littermates. Similar patterns of shape difference were found in both mutants. Increased skull shape variation and a disruption in the covariation of skull structures were observed in G60S/+ mutants only. These results show …

Femoroacetabular Impingement Syndrome: Evaluating Postoperative Rehabilitation Progress And Return To Sport Readiness, Trevor A. Day

Electronic Thesis and Dissertation Repository

Femoroacetabular impingement syndrome (FAIS) is a common cause of non-arthritic hip pain and reduced physical activity in active young adults. It is defined as a motion-related disorder of the hip with a triad of symptoms, clinical signs, and imaging findings that represents symptomatic premature contact between the proximal femur and the acetabulum. There are two anatomical morphologies that can cause FAIS, cam, and pincer, and is a challenging clinical pathology. Patients typically undergo hip arthroscopy to repair damage to the joint and recess the bone causing the impingement. These procedures can result in positive outcomes for the patient, like reduced …

The Role Of Pannexin 3 In Forced Exercise Bone Remodelling And Its Potential Implications For Osteoarthritis, Justin Tang

Undergraduate Student Research Internships Conference

Exercise such as running has been hypothesized to be a factor of osteoarthritis development. However, the relationship is unclear as differences in genetic backgrounds may influence the risk of osteoarthritis (OA). The gene Panx3 codes for the Pannexin 3 protein (PANX3), a mechanically sensitive channel that allows for the passage of various signalling molecules in both chondrocytes and osteoblasts (Boassa et al., 2007; Penuela et al., 2013; Zhang et al., 2021). We have previously shown PANX3 to be protective in traumatic osteoarthritis, however beneficial in age-induced osteoarthritis (Moon et al., 2021), suggesting that PANX3’s role in osteoarthritis development …

Understanding The Role Of Rhamm In Tumor Load– Mediated Tumor Invasiveness Of Triple Negative Breast Cancer, Ashwin Sritharan, Britney Messam

Undergraduate Student Research Internships Conference

1.Compare the levels of proliferation between RHAMM+/+ and RHAMM -/- MDA-MB-231 spheroids as determined by ki67 and Caspase 3 signaling 2.Compare levels of RHAMM, CD44, Has2, and p-ERK activation between RHAMM+/+ and RHAMM -/- MDA-MB-231 spheroids

Towards Standardized Assessment Of Paraspinal Muscle Using Mri, Hamza Mirza

Undergraduate Student Research Internships Conference

• Common methodological variations in paraspinal muscle (PSM) measurement

significantly affect cross-sectional area and fat percentage measurements.

• The lack of standardization of PSM measurements complicates

comparisons of findings between studies and prevents pooling of

data for meta-analyses.

• Standardization in PSM measurements is needed to move the field forward

Establishing Intratumoral Modulation Therapy As A New Treatment Modality For High Grade Gliomas, Andrew M.A. Deweyert

Electronic Thesis and Dissertation Repository

Glioblastoma (GBM) is the most common and lethal primary brain cancer in adults despite aggressive treatments with surgery and chemo-radiation. Advances in electrotherapeutics offer a foundation for developing new treatment modalities that exploit an innate vulnerability of glioblastoma (GBM). Low intensity, non-ablative electric fields are innocuous to normal neural structure, but incite GBM cell apoptosis by putatively disrupting cytokinesis and transmembrane ion homeostasis. Our collaborative research group is pioneering a new electrotherapeutic technology for GBM called Intratumoral Modulation Therapy (IMT) which uses customized, implanted bioelectrodes to deliver sustained, titratable and focused therapeutic electric fields into tumor-affected brain regions. My work …

Novel Imaging Tools Reveal The Dynamics Of The Myocardial Growth Hormone Secretagogue Receptor In Heart Disease And Heart Failure, Rebecca Sullivan

Electronic Thesis and Dissertation Repository

Heart disease (HD) is the leading cause of mortality worldwide. Currently, diagnosis is based on clinical features, imaging, and circulating cardiac biomarkers. Cardiac imaging technologies, such as echocardiography and cardiac magnetic resonance imaging (cMRI), enable the non-invasive detection of changes in heart function. Although these modalities can detect changes in structure and anatomy, it is usually at later stages, where prevention may not be possible. In conjunction with imaging, circulating biomarkers of heart failure (HF), notably B-type natriuretic peptide (BNP) and cardiac troponin I and T, can be detected with increased levels in the blood. These biomarkers are associated with …

The Role Of Gsk3 Alpha And Beta In Embryonic Craniofacial Development, Harman Jassar

Electronic Thesis and Dissertation Repository

Background: The GSK-3 genes (Gsk3a and Gsk3b) have been known to affect many cellular processes and signaling pathways some of which are implicated in the growth and development of the craniofacial skeleton.

Aim: The purpose of this study was to assess the effect of chondrocyte-specific deletion of Gsk3a and Gsk3b on the size of the mandible and craniofacial skeleton in embryonic mice.

Materials & Methods: Mice were bred to generate cartilage-specific Gsk3a and Gsk3b KO mice. On embryonic day 18.5 (E18.5) the offspring were gathered by caesarian section. Whole mount skeletal staining was completed on the specimens using …

Gabab Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity And Filtering In The Cntnap2 Knock-Out Rat, Dorit Möhrle, Wenxuan Wang, Shawn N Whitehead, Susanne Schmid

Anatomy and Cell Biology Publications

Altered sensory information processing, and auditory processing, in particular, is a common impairment in individuals with autism spectrum disorder (ASD). One prominent hypothesis for the etiology of ASD is an imbalance between neuronal excitation and inhibition. The selective GABA_B receptor agonist R-Baclofen has been shown previously to improve social deficits and repetitive behaviors in several mouse models for neurodevelopmental disorders including ASD, and its formulation Arbaclofen has been shown to ameliorate social avoidance symptoms in some individuals with ASD. The present study investigated whether R-Baclofen can remediate ASD-related altered sensory processing reliant on excitation/inhibition imbalance in the auditory brainstem. …