Biomedical Engineering and Bioengineering Commons^™

Association Of X-Ray Absorptiometry Body Composition Measurements With Basic Anthropometrics And Mortality Hazard, Nir Y. Krakauer, Jesse C. Krakauer

Publications and Research

Dual-energy X-ray absorptiometry (DEXA) is a non-invasive imaging modality that can estimate whole-body and regional composition in terms of fat, lean, and bone mass. We examined the ability of DEXA body composition measures (whole-body, trunk, and limb fat mass and fat-free mass) to predict mortality in conjunction with basic body measures (anthropometrics), expressed using body mass index (BMI) and a body shape index (ABSI). We used data from the 1999–2006 United States National Health and Nutrition Examination Survey (NHANES), with mortality follow-up to 2015. We found that all DEXA-measured masses were highly correlated with each other and with ABSI and …

A Systematic Review And Meta-Analysis On The Efficacy Of Stem Cell Therapy On Bone Brittleness In Mouse Models Of Osteogenesis Imperfecta, Lauren Battle, Shoshana Yakar, Alessandra Carriero

Publications and Research

There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection …

Acute Effect Of High‑Definition And Conventional Tdcs On Exercise Performance And Psychophysiological Responses In Endurance Athletes: A Randomized Controlled Trial, Daniel Gomes Da Silva Machado, Marom Bikson, Abhishek Datta, Egas Caparelli‑Dáquer, Gozde Unal, Abrahão F. Baptista, Edilson Serpeloni Cyrino, Li Min Li, Edgard Morya, Alexandre Moreira, Alexandre Hideki Okano

Publications and Research

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called “conventional” tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg− 1 min− …

Detection Methods And Clinical Applications Of Circulating Tumor Cells In Breast Cancer, Hongyi Zhang, Xiaoyan Lin, Yuan Huang, Minghong Wang, Chunmei Cen, Shasha Tang, Marcia R. Dique, Lu Cai, Manuel A. Luis, Jillian Smollar, Yuan Wan, Fengfeng Cai

Publications and Research

Circulating Tumor Cells (CTCs) are cancer cells that split away from the primary tumor and appear in the circulatory system as singular units or clusters, which was first reported by Dr. Thomas Ashworth in 1869. CTCs migrate and implantation occurs at a new site, in a process commonly known as tumor metastasis. In the case of breast cancer, the tumor cells often migrate into locations such as the lungs, brain, and bones, even during the early stages, and this is a notable characteristic of breast cancer. Survival rates have increased significantly over the past few decades because of progress made …

Heparan Sulfate Proteoglycan Glypican‑1 And Pecam‑1 Cooperate In Shear‑Induced Endothelial Nitric Oxide Production, Anne Marie W. Bartosch, Rick Mathews, Marwa M. Mahmoud, Limary M. Cancel, Zahin S. Haq, John M. Tarbell

Publications and Research

This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress …

Nanoanalytical Analysis Of Bisphosphonate-Driven Alterations Of Microcalcifications Using A 3d Hydrogel System And In Vivo Mouse Model, Jessica L. Ruiz, Joshua D. Hutcheson, Luis Cardoso, Amirala Bakhshian Nik, Alexandra Condado De Abreu, Tan Pham, Fabrizio Buffolo, Sara Busatto, Stefania Frederici, Andrea Ridolfi, Masanori Aikawa, Sergio Bertazzo, Paolo Bergese, Sheldon Weinbaum, Elena Aikawa

Publications and Research

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE−/− mouse was used …

Tissue Engineering Pre-Reads, Ryan M. Williams

Open Educational Resources

This material provides an introduction to a tissue engineering module in an experimental methods in biomedical engineering course. Students are expected to be familiar with this material prior to a pre-assessment taken at the beginning of class as we have condense lecture time this semester.

A Bisphosphonate With A Low Hydroxyapatite Binding Affinity Prevents Bone Loss In Mice After Ovariectomy And Reverses Rapidly With Treatment Cessation, Abigail A. Coffman, Jelena Basta-Pljakic, Rosa M. Guerra, Frank H. Ebetino, Mark W. Lundy, Robert J. Majeska, Mitchell B. Schaffler

Publications and Research

Bisphosphonates (BPs) are a mainstay of osteoporosis treatment; however, concerns about bone health based on oversuppression of remodeling remain. Long-term bone remodeling suppression adversely affects bone material properties with microdamage accumulation and reduced fracture toughness in animals and increases in matrix mineralization and atypical femur fractures in patients. Although a “drug holiday” from BPs to restore remodeling and improve bone quality seems reasonable, clinical BPs have long functional half-lives because of their high hydroxyapatite (HAP) binding affinities. This places a practical limit on the reversibility and effectiveness of a drug holiday. BPs with low HAP affinity and strong osteoclast inhibition …

Age And Sex Differences In Load-Induced Tibial Cortical Bone Surface Strain Maps, Alessandra Carriero, Behzad Javaheri, Neda Bassir Kazeruni, Andrew A. Pitsillides, Sandra J. Shefelbine

Publications and Research

Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano-adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load-related strains vary with age and sex. In this study, full-field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old (aged 10, 22 weeks, and 20 months, respectively), male and female C57BL/6J mice with load applied using a …

Special Issue On Professor John M. Tarbell’S Contribution To Cardiovascular Engineering, Hanjoong Jo, Keefe Manning, John M. Tarbell

Publications and Research

No abstract provided.

When The Brain Plays A Game: Neural Responses To Visual Dynamics During Naturalistic Visual Tasks, Jason Ki

Dissertations and Theses

Many day-to-day tasks involve processing of complex visual information in a continuous stream. While much of our knowledge on visual processing has been established from reductionist approaches in lab-controlled settings, very little is known about the processing of complex dynamic stimuli experienced in everyday scenarios. Traditional investigations employ event-related paradigms that involve presentation of simple stimuli at select locations in visual space and discrete moments in time. In contrast, visual stimuli in real-life are highly dynamic, spatially-heterogeneous, and semantically rich. Moreover, traditional experiments impose unnatural task constraints (e.g., inhibited saccades), thus, it is unclear whether theories developed under the reductionist …

Restoration Of Bone Material And Microstructural Properties After Long-Term Remodeling Suppression, Abigail A. Coffman

Dissertations and Theses

Anti-resorptive drugs, principally bisphosphonates (BPs), are the mainstay of osteoporosis treatment. They work by inhibiting bone resorption/remodeling, thus preventing bone loss. However, long-term suppression of bone resorption adversely affects bone tissue mechanical properties, even while conserving bone mass. Lack of remodeling leads to accumulation of fatigue-induced microdamage, altered matrix mineralization and reduction in normal bone tissue heterogeneity, causing impaired strength and fracture toughness. The most severe consequence to patients, while rare, is Atypical Femur Fractures (i.e., complete fatigue fractures of the femoral shaft). To counteract the effects of long-term remodeling suppression, a temporary break in BP treatment (a "drug holiday) …

Development Of A Biaxial Testing System For Research Of Soft Tissue Biomechanics Using Laboratory Models, Tariq Shameen

Dissertations and Theses

The rupture of the cap tissue layer of a fibroatheroma in human coronary vessels is considered the key event leading to the formation of a thrombus and myocardial infarction, resulting in more than half a million deaths in the US every year. In this study, we are interested in investigating the biomechanics of different elastomer materials that can be used as laboratory models to replicate coronary arteries’ ultimate tensile stress (0.2 - 2.08 MPa). To this end, we developed a biomechanical testing system that allows us to characterize the material properties of small samples with high accuracy and precision. We …

Osteocyte Activity And Skeletal Muscle Relative Gene Expression Profiling After Short-Term Muscle Paralysis, Michelle Gelbs

Dissertations and Theses

Mechanical loading is essential for maintaining bone tissue. Reduced mechanical loading has been shown to have a negative effect on bone, and can result in the development of disuse osteoporosis. Disuse models of muscle inactivity and immobilization, like the Botox model used in this study, result in changes in the bone microarchitecture, the mechanisms behind which are not fully understood. In a previous four-week Botox disuse study, skeletally mature 20- week-old rats experienced degradation of intracortical bone, increased vascular porosity, and decreased osteocyte lacunar density in the tibiae. The focus of this study was to explicate a potential source of …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Development Of An Injectable Methylcellulose Hydrogel System For Nucleus Pulposus Repair And Regeneration, Nada A. Haq-Siddiqi

Dissertations and Theses

Low back pain is the most common cause of disability in the world and is often caused by degeneration or injury of the intervertebral disc (IVD). The IVD is a complex, fibrocartilaginous tissue that allows for the wide range of spinal mobility. Disc degeneration is a progressive condition believed to begin in the central, gelatinous nucleus pulposus (NP) region of the tissue, for which there are few preventative therapies. Current therapeutic strategies include pain management and exercise, or surgical intervention such as spinal fusion, none of which address the underlying cause of degeneration. With an increasingly aging population, the socioeconomic …

Feasibility Of Continuous Fever Monitoring Using Wearable Devices, Benjamin L. Smarr, Kirstin Aschbacher, Sarah M. Fisher, Anoushka Chowdhary, Stephan Dilchert, Karena Puldon, Adam Rao, Frederick M. Hecht, Ashley E. Mason

Publications and Research

Elevated core temperature constitutes an important biomarker for COVID-19 infection; however, no standards currently exist to monitor fever using wearable peripheral temperature sensors. Evidence that sensors could be used to develop fever monitoring capabilities would enable large-scale health-monitoring research and provide high-temporal resolution data on fever responses across heterogeneous populations. We launched the TemPredict study in March of 2020 to capture continuous physiological data, including peripheral temperature, from a commercially available wearable device during the novel coronavirus pandemic. We coupled these data with symptom reports and COVID-19 diagnosis data. Here we report findings from the first 50 subjects who reported …

Improve The Prototype Of Low-Cost Near-Infrared Diffuse Optical Imaging System, Chen Xu, Mohammed Z. Shakil

Publications and Research

Diffuse Optical Tomography (DOT) and Optical Spectroscopy using near-infrared (NIR) diffused light has demonstrated great potential for the initial diagnosis of tumors and in the assessment of tumor vasculature response to neoadjuvant chemotherapy. The aims of this project are 1) to test the different types of LEDs in the near-infrared range, and design the driving circuit, and test the modulation of LEDs at different frequencies; 2) to test the APDs as a detector, and build the receiver system and compare efficiency with pre-built systems. In this project, we are focusing on creating a low-cost infrared transmission system for tumor and …

Network-Level Mechanisms Underlying Effects Of Transcranial Direct Current Stimulation (Tdcs) On Visuomotor Learning, Pejman Sehatpour, Clément Dondé, Matthew J. Hoptman, Johanna Kreither, Devin Adair, Elisa Dias, Blair Vail, Stephanie Rohrig, Gail Silipo, Javier Lopez-Calderon, Antigona Martinez, Daniel C. Javitt

Publications and Research

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant (p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence (p <.0001) and fMRI connectivity (p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

Multimodal Computational Modeling Of Visual Object Recognition Deficits But Intact Repetition Priming In Schizophrenia, Pejman Sehatpour, Anahita Bassir Nia, Devin Adair, Zhishun Wang, Heloise M. Debaun, Gail Silipo, Antigona Martinez, Daniel C. Javitt

Publications and Research

The term perceptual closure refers to the neural processes responsible for “filling-in” missing information in the visual image under highly adverse viewing conditions such as fog or camouflage. Here we used a closure task that required the participants to identify barely recognizable fragmented line-drawings of common objects. Patients with schizophrenia have been shown to perform poorly on this task. Following priming, controls and importantly patients can complete the line-drawings at greater levels of fragmentation behaviorally, suggesting an improvement in their ability to performthe task. Closure phenomena have been shown to involve a distributed network of cortical regions, notably the lateral …

Update On The Use Of Transcranial Electrical Brain Stimulation To Manage Acute And Chronic Covid-19 Symptoms, Giuseppina Pilloni, Marom Bikson, Bashar W. Badran, Mark S. George, Steven A. Kautz, Alexandre Hideki Okano, Abrahão Fontes Baptista, Leigh E. Charvet

Publications and Research

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, …

The Glycocalyx And Its Role In Vascular Physiology And Vascular Related Diseases, Sheldon Weinbaum, Limary M. Cancel, Bingmei M. Fu, John M. Tarbell

Publications and Research

Purpose—In 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121–167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.

Methods—A literature search mainly focusing on the role of the glycocalyx in the two major areas described above …

Renal Proximal Tubular Nemo Plays A Critical Role In Ischemic Acute Kidney Injury, Sang Jun Han, Ryan M. Williams, Mihwa Kim, Daniel A. Heller, Vivette D'Agati, Marc Schmidt-Supprian, H. Thomas Lee

Publications and Research

We determined that renal proximal tubular (PT) NF-κB essential modulator (NEMO) plays a direct and critical role in ischemic acute kidney injury (AKI) using mice lacking renal PT NEMO and by targeted renal PT NEMO inhibition with mesoscale nanoparticle–encapsulated NEMO binding peptide (NBP MNP). We subjected renal PT NEMO–deficient mice, WT mice, and C57BL/6 mice to sham surgery or 30 minutes of renal ischemia and reperfusion (IR). C57BL/6 mice received NBP MNP or empty MNP before renal IR injury. Mice treated with NBP MNP and mice deficient in renal PT NEMO were protected against ischemic AKI, having decreased renal tubular …

Rectus Femoris Hyperreflexia Contributes To Stiff-Knee Gait After Stroke, Tunc Akbas, Kyoungsoon Kim, Kathleen Doyle, Kathleen Manella, Robert Lee, Patrick Spicer, Maria Knikou, James Sulzer

Publications and Research

Background: Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to originate from excessive quadriceps activation.However, it is unclear whether hyperreflexia plays a role in this activation. The goal of this study was to establish the relationship between quadriceps hyperreflexia and knee flexion angle during walking in post-stroke SKG.

Methods: The rectus femoris (RF) H-reflex was recorded in 10 participants with post-stroke SKG and 10 healthy controls during standing and walking at the pre-swing phase. In order to attribute the pathological neuromodulation to quadriceps muscle …

Visually Evoked Responses Are Enhanced When Engaging In A Video Game, Jason J. Ki, Lucas C. Parra, Jacek P. Dmochowski

Publications and Research

While it is well known that vision guides movement, less appreciated is that the motor cortex also provides input to the visual system. Here, we asked whether neural processing of visual stimuli is acutely modulated during motor activity, hypothesizing that visual evoked responses are enhanced when engaged in a motor task that depends on the visual stimulus. To test this, we told participants that their brain activity was controlling a video game that was in fact the playback of a prerecorded game. The deception, which was effective in half of participants, aimed to engage the motor system while avoiding evoked …

Olfaction Modulates Inter-Subject Correlation Of Neural Responses, Paul Deguzman, Anshul Jain, Matthias H. Tabert, Lucas C. Parra

Publications and Research

Odors can be powerful stimulants. It is well-established that odors provide strong cues for recall of locations, people and events. The effects of specific scents on other cognitive functions are less well-established. We hypothesized that scents with different odor qualities will have a different effect on attention. To assess attention, we used Inter-Subject Correlation of the EEG because this metric is strongly modulated by attentional engagement with natural audiovisual stimuli.We predicted that scents known to be “energizing” would increase Inter-Subject Correlation during watching of videos as compared to “calming” scents. In a first experiment, we confirmed this for eucalyptol and …

Functional Connectivity Of Eeg Is Subject-Specific, Associated With Phenotype, And Different From Fmri, Maximilian Nentwich, Lei Ai, Jens Madsen, Qawi K. Telesford, Stefan Haufe, Michael P. Milham, Lucas C. Parra

Publications and Research

A variety of psychiatric, behavioral and cognitive phenotypes have been linked to brain ‘’functional connectivity’’ -- the pattern of correlation observed between different brain regions. Most commonly assessed using functional magnetic resonance imaging (fMRI), here, we investigate the connectivity-phenotype associations with functional connectivity measured with electroencephalography (EEG), using phase-coupling. We analyzed data from the publicly available Healthy Brain Network Biobank. This database compiles a growing sample of children and adolescents, currently encompassing 1657 individuals. Among a variety of assessment instruments we focus on ten phenotypic and additional demographic measures that capture most of the variance in this sample. The largest …

Can Transcranial Electrical Stimulation Motor Threshold Estimate Individualized Tdcs Doses Over The Prefrontal Cortex? Evidence From Reverse-Calculation Electric Field Modeling, Kevin A. Caulfield, Bashar W. Badran, Xingbao Li, Marom Bikson, Mark S. George

Publications and Research

No abstract provided.

Otx2 Represses Sister Cell Fate Choices In The Developing Retina To Promote Photoreceptor Specification, Miruna Georgiana Ghinia Tegla, Diego F. Buenaventura, Diana Y. Kim, Cassandra Thakurdin, Kevin C. Gonzalez, Mark M. Emerson

Publications and Research

During vertebrate retinal development, subsets of progenitor cells generate progeny in a non-stochastic manner, suggesting that these decisions are tightly regulated. However, the gene-regulatory network components that are functionally important in these progenitor cells are largely unknown. Here we identify a functional role for the OTX2 transcription factor in this process. CRISPR/Cas9 gene editing was used to produce somatic mutations of OTX2 in the chick retina and identified similar phenotypes to those observed in human patients. Single cell RNA sequencing was used to determine the functional consequences OTX2 gene editing on the population of cells derived from OTX2-expressing retinal progenitor …

Transcranial Electrical Stimulation Motor Threshold Can Estimate Individualized Tdcs Dosage From Reverse-Calculation Electric-Field Modeling, Kevin A. Caulfield, Bashar W. Badran, William H. Devries, Philipp M. Summers, Emma Kofmehl, Xingbao Li, Jeffrey J. Borckardt, Marom Bikson, Mark S. George

Publications and Research

Background

Unique amongst brain stimulation tools, transcranial direct current stimulation (tDCS) currently lacks an easy or widely implemented method for individualizing dosage.

Objective

We developed a method of reverse-calculating electric-field (E-field) models based on Magnetic Resonance Imaging (MRI) scans that can estimate individualized tDCS dose. We also evaluated an MRI-free method of individualizing tDCS dose by measuring transcranial magnetic stimulation (TMS) motor threshold (MT) and single pulse, suprathreshold transcranial electrical stimulation (TES) MT and regressing it against E-field modeling. Key assumptions of reverse-calculation E-field modeling, including the size of region of interest (ROI) analysis and the linearity of multiple E-field …