Investigating the Effects of Hypoxemia on Traumatic Brain Injury

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), 2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Stuart Fries

Advances in non-invasive biosensing measures to monitor wound healing progression

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed

Planetary Defense team project: READI (Roadmap for EArth Defense Initiatives)

Planetary Defense is a complex problem, not well understood by policy makers and the general public. The recent Chelyabinsk incident in Russia created temporary international attention but has failed to effectively stimulate public action. The lack of long-term attention to cosmic hazards has resulted in limited funding to defend our planet. Hence, it is hard to realistically address this challenge and achieve the high test and operational readiness needed for an effective Planetary Defense strategy. To address this problem, we have created a set of recommendations for the development of a Planetary Defense Program, for the purpose of contributing to the protection of Earth from asteroids and comets. The SSP15 READI Project focused on threats for which there is only a short-term warning, specifically a warning of two years or less from detection of the object to impact. We have provided recommendations in five areas of Planetary Defense including detection and tracking, deflection techniques, global collaboration, outreach and education, and evacuation and recovery. We have applied this set of recommendations in a narrative scenario to make our report more impactful and engaging. We contrast optimistic and pessimistic outcomes for a comet threat, differing from each other in terms of the level of readiness achieved during the years leading up to the discovery of the threat. In our optimistic scenario, the deflection system has achieved high test and operational readiness. The world’s governments have realized the importance of being prepared against cosmic hazards and put in place all of the necessary measures for a successful defense, leading to a positive deflection of the comet. In contrast, in the pessimistic scenario no preparation is done before the detection, and the comet strikes a heavily populated area releasing energy equivalent to 80 times the most powerful nuclear bomb ever detonated. The recommendations that we have identified in this report constitute a roadmap to avoid this horrible outcome, and we believe they should be taken seriously and swiftly implemented

Axonal Injury in White Matter after Secondary Hypoxemia in a TBI Model

From the Washington University Undergraduate Research Digest: WUURD, Volume 11, 2015-2016. Published by the Office of Undergraduate Research, Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Kristin Sobotka, Editor; Jennifer Kohl. Mentor: Stuart Fries

How I do it: Pedal access and pedal loop revascularization for patients with chronic limb-threatening ischemia

An increasing proportion of patients with chronic limb-threatening ischemia are older and have multiple comorbidities, including diabetes and renal failure. For those who are not candidates for a surgical bypass, this set of patients presents a challenge to vascular surgeons and interventionalists owing to the complex below-the-knee and increasingly below-the-ankle disease pattern that can fail traditional approaches for endovascular intervention. Two techniques, the retrograde pedal access and the pedal-plantar loop technique, can be useful in these settings and in skilled hands can be used safely, with a high technical success rate. In patients with chronic limb-threatening ischemia who are not candidates for a single-segment saphenous vein bypass, the retrograde pedal access technique can be used not only in the setting of failed antegrade treatment, but also primarily when faced with a difficult groin or as an adjunct during a planned antegrade-retrograde intervention. The pedal plantar loop technique allows for retrograde access to tibial vessels without retrograde vessel puncture and additionally offers the ability to treat the pedal-plantar arch, which may have added benefit in wound healing. We describe the tips and tricks for these two techniques used in our limb salvage practice

Advances in non-invasive biosensing measures to monitor wound healing progression

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed

Attenuating Fibrotic Markers of Patient-Derived Dermal Fibroblasts by Thiolated Lignin Composites

Engineering composite biomaterials requires the successful integration of multiple feed- stocks to formulate a final product for functional improvement. Here we engineered biomaterial scaffolds to attenuate the fibrotic phenotype exhibited by high scarring (HS) patient-derived der- mal fibroblasts (hdFBs) by valorizing lignosulfonate from waste feedstocks of lignin. We utilized phenolic functional groups of lignosulfonate to impart antioxidant properties and the cell binding domains of gelatin to enhance cell adhesion for poly(ethylene glycol)-based scaffolds. Highly ef- ficient chemoselective thiol-ene chemistry was utilized for the formation of composites with thio- lated lignosulfonate (TLS) and methacrylated fish gelatin (fGelMA) in the PEG(poly (ethylene gly- col))-diacrylate matrix. Antioxidant properties of lignosulfonate was not altered after thiolation and the levels of antioxidation were comparable to a well-known antioxidant, L-ascorbic acid, as evi- denced by DPPH (2,2-diphenyl-1-picrylhydrazyl) and TAC (Total Antioxidant Capacity) assays. Unlike porcine gelatin, fGelMA remained liquid at room temperature and exhibited low viscosities, resulting in no issues of miscibility when mixed with PEG. PEG-fGelMA-TLS composites signifi- cantly reduced the differential of five different fibrotic markers (COL1A1, ACTA2, TGFB1 and HIF1A) between HS and low scarring (LS) hdFBs, providing the potential utility of TLS in a bio- material scaffold to attenuate fibrotic responses. </div

Impact of the coronavirus disease 2019 pandemic on surgical research and lessons for the future

The current coronavirus disease 2019 pandemic has had an unprecedented impact on all physicians and has resulted in dramatic changes to clinical and research operations. No study has yet looked at the impact of coronavirus disease 2019 on the surgical research community. In this study, we sought to understand the impact of the pandemic and its associated restrictions on academic surgeons. We surveyed members of the Association for Academic Surgery and the Society of University Surgeons. Survey questions included demographics, current challenges to basic and clinical research activities, attitudes toward remote work and productivity maintenance, and the solutions implemented to maintain productivity. Of 301 respondents, 70% cited a negative impact on research productivity due to mandatory building shutdowns, minimized personnel as a result of social distancing, and suspensions of animal work and clinical trials, with senior faculty and division chiefs and chairs more likely to report a negative impact (P = .001). Only 11% of respondents are documenting their financial losses, and only 19% indicated they received appropriate guidance regarding why and how to monitor the financial impact of the pandemic. Researchers have attempted to maintain research productivity through a focus on remote work, including manuscript writing, grant writing, and data analysis. Some participants have found silver linings, including more time to dedicate to research and family as a result of fewer clinical duties. Productivity strategies developed during the pandemic, including writing, remote work and meetings, and structured scheduling, are lessons that will allow the surgical research community to be resilient in the face of future disruptions