Medical Specialties Commons^™

The Mitochondrial Protease Lonp1 Promotes Proteasome Inhibitor Resistance In Multiple Myeloma, Laure Maneix, Melanie A Sweeney, Sukyeong Lee, Polina Iakova, Shannon E Moree, Ergun Sahin, Premal Lulla, Sarvari V Yellapragada, Francis T F Tsai, Andre Catic

Faculty, Staff and Students Publications

Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in the US. Proteasome inhibitors are an essential part of several standard drug combinations used to treat this incurable cancer. These drugs interfere with the main pathway of protein degradation and lead to the accumulation of damaged proteins inside cells. Despite promising initial responses, multiple myeloma cells eventually become drug resistant in most patients. The biology behind relapsed/refractory multiple myeloma is complex and poorly understood. Several studies provide evidence that in addition to the proteasome, mitochondrial proteases can also contribute to protein quality control outside of …

Hello Darkness My Old Friend: An Experience Of A Transformative Session With Zero Balancing, James Mccormick

Journal of Transformative Touch

An Experience of a Transformative Session with Zero Balancing showing the effects of client experiencing an expanded state of consciousness furring a Zero Balancing session.

A Standard Calculation Methodology For Human Doubly Labeled Water Studies, John R Speakman, Yosuke Yamada, Hiroyuki Sagayama, Elena S F Berman, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Seth A Creasy, Sai Krupa Das, Richard Cooper, Lara R Dugas, Cara B Ebbeling, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, David S Ludwig, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Edward L Melanson, Amy H Luke, Herman Pontzer, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong

Children’s Nutrition Research Center Staff Publications

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Aberrant Azin2 And Polyamine Metabolism Precipitates Tau Neuropathology, Leslie A. Sandusky-Beltran, Andrii Kovalenko, Devon S. Placides, Kevin Ratnasamy, Chao Ma, Jerry B. Hunt, Huimin Liang, John Ivan T. Calahatian, Camilla Michalski, Margaret Fahnestock, Laura J. Blair, April L. Darling, Jeremy D. Baker, Sarah N. Fontaine, Chad A. Dickey, Joshua J. Gamsby, Kevin R. Nash, Erin L. Abner, Maj-Linda B. Selenica, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell’s response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer’s disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to …

Laboratory Markers Predictive Of Fulminant Clostridioides Difficile Infection Refractory To Fluid Resuscitation, Omar Ahmad, Timothy N. Crawford, Vaneet Arora, Mitu Karki Maskey

Internal Medicine Faculty Publications

Background

Old age, leucocytosis, hypoalbuminemia, and elevated creatinine have been identified as risk factors for fulminant Clostridioides difficile infection (CDI). High ATLAS scores have also been linked to fatal disease. The affiliated studies, however, involved patients prescribed metronidazole - a regimen no longer standard of care. The variables were thus reassessed in patients prescribed optimal therapy.

Methods

Adults hospitalized with CDI at University of Kentucky Medical Center were retrospectively reviewed. Enrolled subjects were separated according to disease classification i.e. non-severe/severe versus fulminant CDI. Fulminant patients were further subdivided into hypotensive persons responsive to fluid resuscitation, and those with sequent shock, …

Genetic Variants And Physical Activity Interact To Affect Bone Density In Hispanic Children, Ruixue Hou, Shelley A Cole, Mariaelisa Graff, Yujie Wang, Karin Haack, Sandra Laston, Nitesh R Mehta, Roman J Shypailo, Margaret L Gourlay, Anthony G Comuzzie, Kari E North, Nancy F Butte, Venkata Saroja Voruganti

Children’s Nutrition Research Center Staff Publications

Background: Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.

Methods: Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine …

Mapk4 Promotes Prostate Cancer By Concerted Activation Of Androgen Receptor And Akt, Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M Ittmann, Chad J Creighton, Yingnan Bian, Yanling Meng, David R Rowley, Peter S Nelson, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second leading cause of cancer death in American men. Androgen receptor (AR) signaling is essential for PCa cell growth/survival and remains a key therapeutic target for lethal castration-resistant PCa (CRPC). GATA2 is a pioneer transcription factor crucial for inducing AR expression/activation. We recently reported that MAPK4, an atypical MAPK, promotes tumor progression via noncanonical activation of AKT. Here, we demonstrated that MAPK4 activated AR by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination/degradation. MAPK4 expression correlated with AR activation in human CRPC. Concerted activation of both GATA2/AR and AKT by …

Targeting Nsd2-Mediated Src-3 Liquid-Liquid Phase Separation Sensitizes Bortezomib Treatment In Multiple Myeloma, Jing Liu, Ying Xie, Jing Guo, Xin Li, Jingjing Wang, Hongmei Jiang, Ziyi Peng, Jingya Wang, Sheng Wang, Qian Li, Linquan Ye, Yuping Zhong, Qiguo Zhang, Xiaozhi Liu, David M Lonard, Jin Wang, Bert W O'Malley, Zhiqiang Liu

Faculty, Staff and Students Publications

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone …

Long-Term Effects Of Very Low Dose Particle Radiation On Gene Expression In The Heart: Degenerative Disease Risks, Venkata Naga Srikanth Garikipati, Arsen Arakelyan, Eleanor A Blakely, Polly Y Chang, May M Truongcao, Maria Cimini, Vandana Malaredy, Anamika Bajpai, Sankar Addya, Malik Bisserier, Agnieszka Brojakowska, Abrisham Eskandari, Mary K Khlgatian, Lahouaria Hadri, Kenneth M Fish, Raj Kishore, David A Goukassian

Kimmel Cancer Center Faculty Papers

Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were …

Characterization Of Two Zygnema Strains (Zygnema Circumcarinatum Sag 698-1a And Sag 698-1b) And A Rapid Method To Estimate Nuclear Genome Size Of Zygnematophycean Green Algae, Xuehuan Feng, Andreas Holzinger, Charlotte Permann, Dirk Anderson, Yanbin Yin

Food for Health: Publications

Zygnematophyceae green algae (ZGA) have been shown to be the closest relatives of land plants. Three nuclear genomes (Spirogloea muscicola, Mesotaenium endlicherianum, and Penium margaritaceum) of ZGA have been recently published, and more genomes are underway. Here we analyzed two Zygnema circumcarinatum strains SAG 698-1a (mating +) and SAG 698-1b (mating −) and found distinct cell sizes and other morphological differences. The molecular identities of the two strains were further investigated by sequencing their 18S rRNA, psaA and rbcL genes. These marker genes of SAG 698-1a were surprisingly much more similar to Z. cylindricum (SAG 698-2) than to SAG 698-1b. …

Characterization Of Two Zygnema Strains (Zygnema Circumcarinatum Sag 698-1a And Sag 698-1b) And A Rapid Method To Estimate Nuclear Genome Size Of Zygnematophycean Green Algae, Xuehuan Feng, Andreas Holzinger, Charlotte Permann, Dirk Anderson, Yanbin Yin

Food for Health: Publications

Zygnematophyceae green algae (ZGA) have been shown to be the closest relatives of land plants. Three nuclear genomes (Spirogloea muscicola, Mesotaenium endlicherianum, and Penium margaritaceum) of ZGA have been recently published, and more genomes are underway. Here we analyzed two Zygnema circumcarinatum strains SAG 698-1a (mating +) and SAG 698-1b (mating −) and found distinct cell sizes and other morphological differences. The molecular identities of the two strains were further investigated by sequencing their 18S rRNA, psaA and rbcL genes. These marker genes of SAG 698-1a were surprisingly much more similar to Z. cylindricum (SAG 698-2) than to SAG 698-1b. …

Characterization Of Two Zygnema Strains (Zygnema Circumcarinatum Sag 698-1a And Sag 698-1b) And A Rapid Method To Estimate Nuclear Genome Size Of Zygnematophycean Green Algae, Xuehuan Feng, Andreas Holzinger, Charlotte Permann, Dirk Anderson, Yanbin Yin

Food for Health: Publications

Zygnematophyceae green algae (ZGA) have been shown to be the closest relatives of land plants. Three nuclear genomes (Spirogloea muscicola, Mesotaenium endlicherianum, and Penium margaritaceum) of ZGA have been recently published, and more genomes are underway. Here we analyzed two Zygnema circumcarinatum strains SAG 698-1a (mating +) and SAG 698-1b (mating −) and found distinct cell sizes and other morphological differences. The molecular identities of the two strains were further investigated by sequencing their 18S rRNA, psaA and rbcL genes. These marker genes of SAG 698-1a were surprisingly much more similar to Z. cylindricum (SAG 698-2) than to SAG 698-1b. …

Aberrant Maturation Of The Uncinate Fasciculus Follows Exposure To Unpredictable Patterns Of Maternal Signals, Steven J. Granger, Laura M. Glynn, Curt A. Sandman, Steven L. Small, Andre Obenaus, David B. Keator, Tallie Z. Baram, Hal S. Stern, Michael A. Yassa, Elyssia Poggi Davis

Psychology Faculty Articles and Research

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother–child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key …

The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias

Faculty, Staff and Students Publications

The dentate gyrus (DG) controls information flow into the hippocampus and is critical for learning, memory, pattern separation, and spatial coding, while DG dysfunction is associated with neuropsychiatric disorders. Despite its importance, the molecular mechanisms regulating DG neural circuit assembly and function remain unclear. Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and associated memory processes. In the hippocampus, Tiam1 is predominantly expressed in the DG throughout life. Global deletion of Tiam1 in male mice results in DG granule cells with simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission. Notably, DG …

Machine Intelligence Identifies Soluble Tnfa As A Therapeutic Target For Spinal Cord Injury, J. R. Huie, A. R. Ferguson, N. Kyritsis, J. Z. Pan, K.-A. Irvine, J. L. Nielson, P. G. Schupp, M. C. Oldham, John C. Gensel, A. Lin, M. R. Segal, R. R. Ratan, J. C. Bresnahan, M. S. Beattie

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five …

Assessment Of Major Depressive Disorders Through Neuroimaging Studies And Their Treatment Methods, Jevetha Vijayadasan, Diksha Raghunathan, Sivakumar Rajagopal, Rahul Soangra

Physical Therapy Faculty Articles and Research

Many mental disorders are caused due to improper regulation of the brain and depression is one such. It affects both children and adults and is very common among teenagers. There are many challenges clinicians face regarding the management of this disease. These challenges have prompted the development of various neuroimaging techniques that effectively diagnose the condition. The main techniques are Magnetic resonance imaging (MRI) and Positron emission tomography (PET) which have gained momentum over the years. Advanced MRI techniques help study certain regions of the brain such as hippocampus and amygdala. Effective treatments for depression include antidepressant medications and brain …

Vertical Sleeve Gastrectomy Confers Metabolic Improvements By Reducing Intestinal Bile Acids And Lipid Absorption In Mice, Lili Ding, Eryun Zhang, Qiaoling Yang, Lihua Jin, Kyle M Sousa, Bingning Dong, Yangmeng Wang, Jui Tu, Xiaoxiao Ma, Jingyan Tian, Hongli Zhang, Zhipeng Fang, Ana Guan, Yixin Zhang, Zhengtao Wang, David D Moore, Li Yang, Wendong Huang

Faculty, Staff and Students Publications

Vertical sleeve gastrectomy (VSG) is a highly effective bariatric surgery that sustainably treats obesity and type 2 diabetes (T2D). However, the underlying mechanisms governing its metabolic benefits remain unclear. In this study, we have used four different genetically modified mouse lines to understand the link between bile acid circulation and metabolic effects of VSG. Instead of directly activating the nuclear bile acid receptor farnesoid X receptor (Fxr) in the liver or intestine, VSG reduces intestinal levels of bile acids, thereby decreasing fat absorption in the intestine. Given the rising popularity of bariatric surgeries to treat obesity and associated T2D, the …

Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, …

Hermansky-Pudlak Syndrome-2 Alters Mitochondrial Homeostasis In The Alveolar Epithelium Of The Lung, Karina Cuevas-Mora, Willy Roque, Hoora Shaghaghi, Bernadette R Gochuico, Ivan O Rosas, Ross Summer, Freddy Romero

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial dysfunction has emerged as an important player in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a common cause of idiopathic interstitial lung disease in adults. Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that causes a similar type of pulmonary fibrosis in younger adults, although the role of mitochondrial dysfunction in this condition is not understood.

METHODS: We performed a detailed characterization of mitochondrial structure and function in lung tissues and alveolar epithelial cells deficient in the adaptor protein complex 3 beta 1 (Ap3b1) subunit, the gene responsible for causing subtype 2 of HPS (HPS-2).

RESULTS: We …

Common Questions And Misconceptions About Creatine Supplementation: What Does The Scientific Evidence Really Show?, Jose Antonio, Darren G Candow, Scott C Forbes, Bruno Gualano, Andrew R Jagim, Richard B Kreider, Eric S Rawson, Abbie E Smith-Ryan, Trisha A Vandusseldorp, Darryn S Willoughby, Tim N Ziegenfuss

Faculty, Staff and Students Publications

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. …

Cryo-Electron Tomography Of Candida Glabrata Plasma Membrane Proteins, Cristina Jiménez-Ortigosa, Jennifer Jiang, Muyuan Chen, Xuyuan Kuang, Kelley R Healey, Paul Castellano, Nikpreet Boparai, Steven J Ludtke, David S Perlin, Wei Dai

Faculty, Staff and Students Publications

Fungal plasma membrane proteins have long been recognized as targets for the development of antifungal agents. Despite recent progress in experimental approaches and computational structural predictions, our knowledge of the structural dynamics and spatial distribution of these membrane proteins in the context of their native lipid environment remains limited. By applying cryo-electron tomography (cryoET) and subtomogram analysis, we aim to characterize the structural characteristics and spatial distribution of membrane proteins present in Candida glabrata plasma membranes. This study has resulted in the identification of the membrane-embedded structure of the fungal H+-ATPase, Pma1. Tomograms of the plasma membrane revealed that Pma1 …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …

Novel Influences Of Sex And Apoe Genotype On Spinal Plasticity And Recovery Of Function After Spinal Cord Injury, Lydia E. Strattan, Daimen R. Britsch, Chris M. Calulot, Rachel S. J. Maggard, Erin L. Abner, Lance A. Johnson, Warren J. Alilain

Sanders-Brown Center on Aging Faculty Publications

Spinal cord injuries can abolish both motor and sensory function throughout the body. Spontaneous recovery after injury is limited and can vary substantially between individuals. Despite an abundance of therapeutic approaches that have shown promise in preclinical models, there is currently a lack of effective treatment strategies that have been translated to restore function after SCI in the human population. We hypothesized that sex and genetic background of injured individuals could impact how they respond to treatment strategies, presenting a barrier to translating therapies that are not tailored to the individual. One gene of particular interest is APOE, which has …

Eosinophils Attenuate Hepatic Ischemia-Reperfusion Injury In Mice Through St2-Dependent Il-13 Production, Yaochun Wang, Yang Yang, Meng Wang, Shuhong Wang, Jong-Min Jeong, Long Xu, Yankai Wen, Christoph Emontzpohl, Constance Lynn Atkins, Kevin Duong, Nicolas F Moreno, Xiaoyi Yuan, David R Hall, Wasim Dar, Dechun Feng, Bin Gao, Yong Xu, Zoltan Czigany, Sean P Colgan, J Steve Bynon, Shizuo Akira, Jared M Brown, Holger K Eltzschig, Elizabeth A Jacobsen, Cynthia Ju

Faculty, Staff and Students Publications

Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified …

Lkb1 And Ampk Instruct Cone Nuclear Position To Modify Visual Function, Courtney A Burger, Nicholas E Albrecht, Danye Jiang, Justine H Liang, Ross A Poché, Melanie A Samuel

Faculty, Staff and Students Publications

Cone photoreceptors detect light and are responsible for color vision. These cells display a distinct polarized morphology where nuclei are precisely aligned in the apical retina. However, little is known about the mechanisms involved in cone nuclear positioning or the impact of this organization on retina function. We show that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate cone nuclear positioning. In the absence of either molecule, cone nuclei are misplaced along the axon, resulting in altered nuclear lamination. LKB1 is required specifically in cones to mediate this process, and disruptions in nuclear alignment result in reduced …

Hospital-Acquired Venous Thromboembolism Or Bleeding Following Total Joint Arthroplasty: A Systematic Review And Meta-Analysis For The Association Of The Gene Polymorphism., Michael Debeau

Medical Student Research Symposium

This review seeks to understand the current existing literature on genetic polymorphisms to VTE following orthopedic surgery. Using PRISMA guidelines, 234 studies were retrieved from PubMed and Cochrane. The eligibility assessment yielded 16 studies including a systematic review. A STREGA and STROBE quality assessment found these studies to have high methodological quality. A significant association was found between the PAI-1 4G/4G genotype and resistance to anticoagulation therapy (OR = 2.692; 95% CI = 1.302 - 4.702). Moreover, the MTHFR C677T and A1298C polymorphisms significantly increased the incidence of VTE in patients that are compound heterozygotes (OR = 2.89; 95% CI …

Misty Rhoads Ijzbtt Editorial Welcome, Misty Rhoads

Journal of Transformative Touch

Editorial Welcome to the IJZBTT from the Executive Editor -Dr. Misty Rhoads-

Rapid Decline In Telestroke Consults In The Setting Of Covid-19., Syed O. Shah., Robin Dharia, Jaime Stazi, Maureen Deprince, Robert H. Rosenwasswer

Farber Institute for Neuroscience Faculty Papers

Background and Purpose: As coronavirus disease 2019 (COVID-19) continues to be a global pandemic, there is a growing body of evidence suggesting that incidence of diseases that require emergent care, particularly myocardial infarction and ischemic stroke, has declined rapidly. The objective of this study is to quantify our experience of telestroke (TS) consults at a large tertiary comprehensive stroke center during the COVID-19 pandemic.

Methods: We retrospectively reviewed TS consults of patients presenting to our neuroscience network. Those with a confirmed diagnosis of acute ischemic stroke or transient ischemia attack were included. Data were compared from April 1, 2019, to …

Macrophage-Derived Thrombospondin 1 Promotes Obesity-Associated Non-Alcoholic Fatty Liver Disease, Taesik Gwag, Raja Gopal Reddy Mooli, Dong Li, Sangderk Lee, Eun Young Lee, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Background

Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role.

Methods

High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific Tsp1-knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development.

Results

Liver TSP1 levels were increased in experimental obese …