Biomedical Engineering and Bioengineering Commons^™

Advanced Microstructural Characterization Of Functionally Graded Dental Ceramic Material For Materials-Informed Finishing, Angani Vigneswaran

Theses and Dissertations--Manufacturing Systems Engineering

Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) has gained popularity as the choice of material for dental prosthetics. Ivoclar Vivadent’s IPS e.max ZirCAD Prime dental ceramic incorporates a unique gradient technology that varies the yttria content over the thickness of the material. The top layer is composed of 5Y-TZP which is desired for its optical properties while the bottom layer is composed of a much stronger 3Y-TZP. In between the two layers, 5Y-TZP and 3Y-TZP are mixed to form a transition layer. Varying the amount of yttria allows for more esthetically pleasing translucency in the visible areas of the restoration without compromising …

The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi

Plant Pathology Faculty Publications

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG …

Therapeutic Treatment With The Anti-Inflammatory Drug Candidate Mw151 May Partially Reduce Memory Impairment And Normalizes Hippocampal Metabolic Markers In A Mouse Model Of Comorbid Amyloid And Vascular Pathology, David J. Braun, David K. Powell, Christopher J. Mclouth, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Neuroscience Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop …

Siderophore-Mediated Zinc Acquisition Enhances Enterobacterial Colonization Of The Inflamed Gut, Judith Behnsen, Hui Zhi, Allegra T. Aron, Venkateswaran Subramanian, William Santus, Michael H. Lee, Romana R. Gerner, Daniel Petras, Janet Z. Liu, Keith D. Green, Sarah L. Price, Jose Camacho, Hannah Hillman, Joshua Tjokrosurjo, Nicola P. Montaldo, Evelyn M. Hoover, Sean Treacy-Abarca, Benjamin A. Gilston, Eric P. Skaar, Walter J. Chazin, Sylvie Garneau-Tsodikova, Matthew B Lawrenz, Robert D Perry, Sean-Paul Nuccio, Pieter C. Dorrestein, Manuela Raffatellu

Pharmacy Nuclear Magnetic Resonance Center Faculty Publications

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the …

Multi-Vendor And Multisite Evaluation Of Cerebrovascular Reactivity Mapping Using Hypercapnia Challenge, Peiying Liu, Dengrong Jiang, Marilyn Albert, Christopher E. Bauer, Arvind Caprihan, Brian T. Gold, Steven M. Greenberg, Karl G. Helmer, Kay Jann, Gregory A. Jicha, Pavel Rodriguez, Claudia L Satizabal, Sudha Seshadri, Herpreet Singh, Jeffrey F. Thompson, Danny J. J. Wang, Hanzhang Lu

Neuroscience Faculty Publications

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined. The goal of this report from the MarkVCID small vessel disease biomarkers consortium is to evaluate …

Cessation And Resumption Of Elective Neurointerventional Procedures During The Coronavirus Disease 2019 Pandemic And Future Pandemics, Tim W. Malisch, Sameer A. Ansari, Gary R. Duckwiler, Kyle M. Fargen, Steven W. Hetts, Franklin A. Marden, Athos Patsalides, Clemens M. Schirmer, Allan Brook, Justin F. Fraser

Neurosurgery Faculty Publications

At the time of this writing, the coronavirus disease 2019 pandemic continues to be a global threat, disrupting usual processes, and protocols for delivering health care around the globe. There have been significant regional and national differences in the scope and timing of these disruptions. Many hospitals were forced to temporarily halt elective neurointerventional procedures with the first wave of the pandemic in the spring of 2020, in order to prioritize allocation of resources for acutely ill patients and also to minimize coronavirus disease 2019 transmission risks to non-acute patients, their families, and health care workers. This temporary moratorium on …

Pairwise Correlation Analysis Of The Alzheimer’S Disease Neuroimaging Initiative (Adni) Dataset Reveals Significant Feature Correlation, Erik D. Huckvale, Matthew W. Hodgman, Brianna B. Greenwood, Devorah O. Stucki, Katrisa M. Ward, Mark T. W. Ebbert, John S. K. Kauwe, The Alzheimer’S Disease Neuroimaging Initiative, The Alzheimer’S Disease Metabolomics Consortium, Justin B. Miller

Sanders-Brown Center on Aging Faculty Publications

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.) from Alzheimer’s disease (AD) cases and controls that have recently been used by machine learning algorithms to evaluate AD onset and progression. While using a variety of biomarkers is essential to AD research, highly correlated input features can significantly decrease machine learning model generalizability and performance. Additionally, redundant features unnecessarily increase computational time and resources necessary to train predictive models. Therefore, we used 49,288 biomarkers and 793,600 extracted MRI features to assess feature correlation within the ADNI dataset to determine the …

Bone Quality And Fractures In Women With Osteoporosis Treated With Bisphosphonates For 1 To 14 Years, Hartmut H. Malluche, Jin Chen, Florence Lima, Lucas J. Liu, Marie-Claude Monier-Faugere, David A. Pienkowski

Internal Medicine Faculty Publications

Oral bisphosphonates are the primary medication for osteoporosis, but concerns exist regarding potential bone-quality changes or low-energy fractures. This cross-sectional study used artificial intelligence methods to analyze relationships among bisphosphonate treatment duration, a wide variety of bone-quality parameters, and low-energy fractures. Fourier transform infrared spectroscopy and histomorphometry quantified bone-quality parameters in 67 osteoporotic women treated with oral bisphosphonates for 1 to 14 years. Artificial intelligence methods established two models relating bisphosphonate treatment duration to bone-quality changes and to low-energy clinical fractures. The model relating bisphosphonate treatment duration to bone quality demonstrated optimal performance when treatment durations of 1 to 8 …

In Situ Imaging Of Bacterial Outer Membrane Projections And Associated Protein Complexes Using Electron Cryo-Tomography, Mohammed Kaplan, Georges Chreifi, Lauren Ann Metskas, Janine Liedtke, Cecily R. Wood, Catherine M. Oikonomou, William J. Nicolas, Poorna Subramanian, Lori A. Zacharoff, Yuhang Wang, Yi-Wei Chang, Morgan Beeby, Megan J. Dobro, Yongtao Zhu, Mark J. Mcbride, Ariane Briegel, Carrie L. Shaffer, Grant J. Jensen

Veterinary Science Faculty Publications

The ability to produce outer membrane projections in the form of tubular membrane extensions (MEs) and membrane vesicles (MVs) is a widespread phenomenon among diderm bacteria. Despite this, our knowledge of the ultrastructure of these extensions and their associated protein complexes remains limited. Here, we surveyed the ultrastructure and formation of MEs and MVs, and their associated protein complexes, in tens of thousands of electron cryo-tomograms of ~90 bacterial species that we have collected for various projects over the past 15 years (Jensen lab database), in addition to data generated in the Briegel lab. We identified outer MEs and MVs …

The Effect Of Severe Intraventricular Hemorrhage On The Biorhythms Of Feeding In Premature Infants, Ira H. Gewolb, Babatunde T. Sobowale, Frank L. Vice, Abhijit R. Patwardhan, Nino Solomonia, Eric W. Reynolds

Biomedical Engineering Faculty Publications

Background: Suck-swallow rhythmicity and the integration of breathing into infant feeding are developmentally regulated. Neurological injury and breathing abnormalities can both impact feeding in preterm infants.

Objective: To determine the effects of neurologic injury independent of effects of disordered breathing on feeding biorhythms in premature infants.

Methods: Low-risk preterm infants (LRP), infants with Grade 3–4 Intraventricular Hemorrhage (IVH), those with bronchopulmonary dysplasia (BPD), and those with both BPD and IVH (BPD+IVH) were identified. Forty-seven infants, 32–42 weeks Postmenstrual Age (PMA) were evaluated on one or more occasions (131 studies). Of these, 39 infants (81 studies) were performed at >35 weeks …

Interprofessional Inconsistencies In The Diagnosis Of Shoulder Instability: Survey Results Of Physicians And Rehabilitation Providers, Constantine P. Nicolozakes, Xinning Li, Timothy L. Uhl, Guido Marra, Nitin B. Jain, Eric J. Perreault, Amee L. Seitz

Physical Therapy Faculty Publications

Background: Clinicians of many specialties within sports medicine care for athletes with shoulder instability, but successful outcomes are inconsistent. Consistency across specialties in the diagnosis of shoulder instability is critical for care of the athlete, yet the extent of divergence in its diagnosis is unknown.

Hypothesis: Physicians differ from rehabilitation providers in which findings they deem clinically important to differentiate shoulder instability from impingement, and in how they diagnose athlete scenarios with atraumatic shoulder instability.

Study Design: Cross-sectional study.

Methods: Physicians (orthopaedic surgeons, primary care sports medicine physicians) and rehabilitation providers (physical therapists, athletic trainers) were asked via an online …

Hypertrophic Cardiomyopathy Β-Cardiac Myosin Mutation (P710r) Leads To Hypercontractility By Disrupting Super Relaxed State, Alison Schroer Vander Roest, Chao Liu, Makenna M. Morck, Kristina Bezold Kooiker, Gwanghyun Jung, Dan Song, Aminah Dawood, Arnav Jhingran, Gaspard Pardon, Sara Ranjbarvaziri, Giovanni Fajardo, Mingming Zhao, Kenneth S. Campbell, Beth L. Pruitt, James A. Spudich, Kathleen M. Ruppel, Daniel Bernstein

Physiology Faculty Publications

Hypertrophic cardiomyopathy (HCM) is the most common inherited form of heart disease, associated with over 1,000 mutations, many in β-cardiac myosin (MYH7). Molecular studies of myosin with different HCM mutations have revealed a diversity of effects on ATPase and load-sensitive rate of detachment from actin. It has been difficult to predict how such diverse molecular effects combine to influence forces at the cellular level and further influence cellular phenotypes. This study focused on the P710R mutation that dramatically decreased in vitro motility velocity and actin-activated ATPase, in contrast to other MYH7 mutations. Optical trap measurements of single myosin molecules revealed …

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction In Tauopathy, Shon A. Koren, Matthew J. Hamm, Ryan Cloyd, Sarah N. Fontaine, Emad Chishti, Chiara Lanzillotta, Jennifer Rodriguez-Rivera, Alexandria Ingram, Michelle Bell, Sara M. Galvis-Escobar, Nicholas Zulia, Fabio Di Domenico, Duc Duong, Nicholas T. Seyfried, David K. Powell, Moriel Vandsburger, Tal Frolinger, Anika M. S. Hartz, John Koren Iii, Jeffrey M. Axten, Nicholas J. Laping, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

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 …

Β-Amyloid And Tau Drive Early Alzheimer's Disease Decline While Glucose Hypometabolism Drives Late Decline, Tyler C. Hammond, Xin Xing, Chris Wang, David Ma, Kwangsik Nho, Paul K. Crane, Fanny Elahi, David A. Ziegler, Gongbo Liang, Qiang Cheng, Lucille M. Yanckello, Nathan Jacobs, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer’s disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer’s Disease Neuroimaging Initiative dataset, we show that A/T/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of Aβ …

A Comparative Study Of Sleep And Diurnal Patterns In House Mouse (Mus Musculus) And Spiny Mouse (Acomys Cahirinus), Chanung Wang, Lauren E. Guerriero, Dillon M. Huffman, Asma'a A. Ajwad, Trae C. Brooks, Sridhar Sunderam, Ashley W. Seifert, Bruce F. O'Hara

Biomedical Engineering Faculty Publications

Most published sleep studies use three species: human, house mouse, or Norway rat. The degree to which data from these species captures variability in mammalian sleep remains unclear. To gain insight into mammalian sleep diversity, we examined sleep architecture in the spiny basal murid rodent Acomys cahirinus. First, we used a piezoelectric system validated for Mus musculus to monitor sleep in both species. We also included wild M. musculus to control for alterations generated by laboratory-reared conditions for M. musculus. Using this comparative framework, we found that A. cahirinus, lab M. musculus, and wild M. musculus were …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Barn-Raising On The Digital Frontier: The L.A.U.N.C.H. Collaborative, Bradford W. Hesse, David Ahern, Michele Ellison, Eliah Aronoff-Spencer, Robin C. Vanderpool, Karen Onyeije, Michael C. Gibbons, Timothy W. Mullett, Ming-Yuan Chih, Victoria Attencio, Grant Patterson, Jessica Boten, Christopher Hartshorn, Ben Bartolome, Katie Gorscak, Melanie Mccomsey, Alexandra Hubenko, Bin Huang, Corey Baker, Don Norman

Journal of Appalachian Health

A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches—or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond the clinic—are becoming an indispensable tool in medicine to overcome the obstacle of distance.

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

Early Acid/Base And Electrolyte Changes In Permanent Middle Cerebral Artery Occlusion: Aged Male And Female Rats, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Sarah J. Goodwin, David Powell, Doug Lukins, Justin F. Fraser, Keith R. Pennypacker

Neurosurgery Faculty Publications

BACKGROUND: Early changes in acid/base and electrolyte concentrations could provide insights into the development of neuropathology at the onset of stroke. We evaluated associations between acid/base and electrolyte concentrations, and outcomes in permanent middle cerebral artery occlusion (pMCAO) model.

METHODS: 18-month-old male and female Sprague-Dawley rats underwent pMCAO. Pre-, post- (7 min after occlusion), and at 72 hr of pMCAO venous blood samples provided pH, carbon dioxide, oxygen, glucose, hematocrit, hemoglobin, and electrolyte values of ionized calcium, potassium, and sodium. Multiple linear regression determined predictors of infarct and edema volumes from these values, Kaplan-Meier curve analyzed morality between males and …

Knee Joint Loading Following Anterior Cruciate Ligament Reconstruction: Link To Patient Reported Outcomes And A Novel Method To Monitor With Wearable Sensors, Alex Spencer

Theses and Dissertations--Kinesiology and Health Promotion

Recovery from anterior cruciate ligament reconstruction (ACLR) commonly results in undesirable physical and patient-reported outcomes (PROs). Identification of modifiable factors such as knee contact force (KCF) early in rehabilitation that can improve these outcomes is important due to the rapid decrease in function, quality of life, and joint health in this population. Additionally, if noninvasive measurement of KCFs outside of a traditional laboratory were possible, clinicians could optimize patient treatment with personalized care. Therefore, there are two primary aims to this thesis: 1) quantify the link between KCF and PROs which measure pain, ability to perform activities of daily living, …

Atv Dynamics And Pediatric Rider Safety, James T. Auxier Ii

Theses and Dissertations--Biomedical Engineering

It has been observed through numerous academic and governmental agency studies that pediatric all-terrain vehicle ridership carries significant risk of injury and death. While no doubt valuable to safety, the post-hoc approach employed in these studies does little to explain the why and how behind the risk factors. Furthermore, there has been no prolonged, widespread, organized, and concerted effort to reconstruct and catalog the details and causes of the large (20,000+) number of ATV-related injuries that occur each year as has been done for road-based motor vehicle accidents. This dissertation takes the opposite approach from a meta-analysis and instead examines …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

A Pilot Study Identifying Brain-Targeting Adaptive Immunity In Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury, Sterling B. Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O. Torres, Uma M. Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman, Ann M. Stowe

Neurology Faculty Publications

OBJECTIVES: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

DESIGN: A single center prospective observational study.

SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center.

PATIENTS: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Venous blood samples were …

A Brain-Computer Interface For Closed-Loop Sensory Stimulation During Motor Training In Patients With Tetraplegia, Sarah Helen Thomas

Theses and Dissertations--Biomedical Engineering

Normal movement execution requires proper coupling of motor and sensory activation. An increasing body of literature supports the idea that incorporation of sensory stimulation into motor rehabilitation practices increases its effectiveness. Paired associative stimulation (PAS) studies, in which afferent and efferent pathways are activated in tandem, have brought attention to the importance of well-timed stimulation rather than non-associative (i.e., open-loop) activation. In patients with tetraplegia resulting from spinal cord injury (SCI), varying degrees of upper limb function may remain and could be harnessed for rehabilitation. Incorporating associative sensory stimulation coupled with self-paced motor training would be a means for supplementing …

Calibrated Short Tr Recovery Mri For Rapid Measurement Of Brain-Blood Partition Coefficient And Correction Of Quantitative Cerebral Blood Flow, Scott William Thalman

Theses and Dissertations--Biomedical Engineering

The high prevalence and mortality of cerebrovascular disease has led to the development of several methods to measure cerebral blood flow (CBF) in vivo. One of these, arterial spin labeling (ASL), is a quantitative magnetic resonance imaging (MRI) technique with the advantage that it is completely non-invasive. The quantification of CBF using ASL requires correction for a tissue specific parameter called the brain-blood partition coefficient (BBPC). Despite regional and inter-subject variability in BBPC, the current recommended implementation of ASL uses a constant assumed value of 0.9 mL/g for all regions of the brain, all subjects, and even all species.

The …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …