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Articles 16171 - 16200 of 18368
Full-Text Articles in Entire DC Network
Broken And Forgotten: A Case Of Unintentionally Retained Foreign Object, Hong Loan Nguyen, Lauren Nicholas Herrera, Ali Cheema, Pralay Kumar Sarkar
Broken And Forgotten: A Case Of Unintentionally Retained Foreign Object, Hong Loan Nguyen, Lauren Nicholas Herrera, Ali Cheema, Pralay Kumar Sarkar
Faculty, Staff and Students Publications
Central venous catheter have become ubiquitous with greater than 15 million catheter days/year in the intensive care setting alone. However, the procedure carries with it several immediate and other delayed complications that can result in significant morbidity, mortality, and increased healthcare cost. We report a rare case of significantly delayed complications associated with intravascular loss of guide wire during central venous catheter placement and its impact on patient's long term management. The case highlights not only the importance of proper technique and safety precaution in performing an increasingly common procedure, but also the need for timely identification and rectification of …
Reduced Bacterial Burden Of The Skin Surrounding The Shoulder Joint Following Topical Protocatechuic Acid Application: Results Of A Pilot Study, Omid Jalali, Molly Best, Alison Wong, Brett Schaeffer, Brendon Bauer, Lanny Johnson
Reduced Bacterial Burden Of The Skin Surrounding The Shoulder Joint Following Topical Protocatechuic Acid Application: Results Of A Pilot Study, Omid Jalali, Molly Best, Alison Wong, Brett Schaeffer, Brendon Bauer, Lanny Johnson
Faculty, Staff and Students Publications
BACKGROUND: Reducing the rising health-care burden associated with shoulder surgical site infection (SSI) is of paramount importance. The purpose of this study was to investigate the antimicrobial efficacy of protocatechuic acid (PCA) as a topical reagent for surgical skin antisepsis surrounding the shoulder joint.
METHODS: This was a 2-phase skin-disinfection trial involving the human shoulder. The shoulders of healthy volunteers were randomized to topical treatment with PCA (a 10% concentration of PCA in Phase I [11 subjects] and a 17% concentration in Phase II [12 subjects]), with a control of isopropyl alcohol (IPA) applied to the contralateral shoulder. Mechanical scraping …
Protocatechuic Acid As A Topical Antimicrobial For Surgical Skin Antisepsis: Preclinical Investigations, Omid Jalali, Molly Best, Alison Wong, Brett Schaeffer, Brendon Bauer, Lanny Johnson
Protocatechuic Acid As A Topical Antimicrobial For Surgical Skin Antisepsis: Preclinical Investigations, Omid Jalali, Molly Best, Alison Wong, Brett Schaeffer, Brendon Bauer, Lanny Johnson
Faculty, Staff and Students Publications
BACKGROUND: There is a need for novel skin antiseptic agents to combat the health-care burdens associated with surgical site infection (SSI) and bacterial resistance. The purpose of this proof-of-principle pilot study was to investigate the potential of the phenolic compound protocatechuic acid (PCA) as a topical antimicrobial for surgical skin antisepsis.
METHODS: The Kirby-Bauer method of disc diffusion was used to investigate the in vitro antimicrobial activity and comparative effectiveness of PCA and 7 related compounds against SSI pathogens. To explore the in vivo efficacy of topical PCA for providing deep, penetrating skin antisepsis, living
RESULTS: Compared with other polyphenols, …
The Application Of Machine Learning Models In The Concussion Diagnosis Process, Sujit Subhash
The Application Of Machine Learning Models In The Concussion Diagnosis Process, Sujit Subhash
Masters Theses
“Concussions represent a growing health concern and are challenging to diagnose and manage. Roughly four million concussions are diagnosed every year in the United States. Although research into the application of advanced metrics such as neuroimages and blood biomarkers has shown promise, they are yet to be implemented at a clinical level due to cost and reliability concerns. Therefore, concussion diagnosis is still reliant on clinical evaluations of symptoms, balance, and neurocognitive status and function. The lack of a universal threshold on these assessments makes the diagnosis process entirely reliant on a physician’s interpretation of these assessment scores. This study …
Non-Naturally Occurring Porcine Reproduction And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma
Non-Naturally Occurring Porcine Reproduction And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma
Nebraska Center for Virology: Faculty Publications
A non-naturally occuring porcine reproductive and respiratory syndrome virus (PRRSV) is provided herein, and methods of making and using the non-naturally occurring PRRSV also are provided.
The Effect Of Hibiscus.Sabdariffa. L On Blood Pressure And Arterial Stiffness In Humans, Basirat Tolulope Shittu
The Effect Of Hibiscus.Sabdariffa. L On Blood Pressure And Arterial Stiffness In Humans, Basirat Tolulope Shittu
Dissertations, Master's Theses and Master's Reports
Cardiovascular diseases (CVD) are the foremost cause of death worldwide. The main risk factor for CVD is uncontrolled hypertension (HTN). The prescription of only anti-hypertensive regimens in the management of HTN is becoming more challenging due to the high cost and adverse effects linked to the persistent usage of the drugs. Eighteen participants completed the study by consuming 2g of Hibiscus sabdariffa or oolong tea twice daily for six weeks. We lost an additional twelve participants in the study due to the COVID-19 pandemic. Central arterial stiffness was analyzed as cfPWV using applanation tonometry technique. The HS tea intervention (n=11) …
I Was Determined To Breastfeed, And I Always Found A Solution: Successful Experiences Of Exclusive Breastfeeding Among Chinese Mothers In Ireland, John Kearney, Qianling Zhou, Haoyue Chen, Katherine Younger, Tanya M. Cassidy
I Was Determined To Breastfeed, And I Always Found A Solution: Successful Experiences Of Exclusive Breastfeeding Among Chinese Mothers In Ireland, John Kearney, Qianling Zhou, Haoyue Chen, Katherine Younger, Tanya M. Cassidy
Articles
Background: The prevalence of exclusive breastfeeding for at least 4 months was previously found to be very low among Chinese immigrants in Ireland, at 5.8% (Zhou et al., Front Public Health 6:351, 2018). This study investigates the successful experiences of Chinese mothers living in Ireland who exclusively breastfeed for between four and 6 months.
Methods: Participants were recruited from the sample of the Ireland Chinese Mother Survey. Qualitative in-depth interviews were conducted with fourteen participants in their homes or public places.
Results: A content analysis revealed that various factors contributed to a successful experience of exclusive breastfeeding among the group …
Resistance To Ectromelia Virus Infection Requires Cgas In Bone Marrow-Derived Cells Which Can Be Bypassed With Cgamp Therapy., Eric B. Wong, Brian Montoya, Maria Ferez, Colby Stotesbury, Luis J. Sigal
Resistance To Ectromelia Virus Infection Requires Cgas In Bone Marrow-Derived Cells Which Can Be Bypassed With Cgamp Therapy., Eric B. Wong, Brian Montoya, Maria Ferez, Colby Stotesbury, Luis J. Sigal
Department of Microbiology and Immunology Faculty Papers
Cells sensing infection produce Type I interferons (IFN-I) to stimulate Interferon Stimulated Genes (ISGs) that confer resistance to viruses. During lympho-hematogenous spread of the mouse pathogen ectromelia virus (ECTV), the adaptor STING and the transcription factor IRF7 are required for IFN-I and ISG induction and resistance to ECTV. However, it is unknown which cells sense ECTV and which pathogen recognition receptor (PRR) upstream of STING is required for IFN-I and ISG induction. We found that cyclic-GMP-AMP (cGAMP) synthase (cGAS), a DNA-sensing PRR, is required in bone marrow-derived (BMD) but not in other cells for IFN-I and ISG induction and for …
The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun
The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun
Center for Translational Medicine Faculty Papers
Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …
Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri
Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri
Department of Biochemistry and Molecular Biology Faculty Papers
Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as why …
Altered Central Hemodynamics In Individuals With Down Syndrome, Thessa Irena Maria Hilgenkamp, Elizabeth Cornellia Schroeder, Sang Ouk Wee, Georgios Grigoriadis, Alexander Jacob Rosenberg, Tracy Baynard, Bo Fernhall
Altered Central Hemodynamics In Individuals With Down Syndrome, Thessa Irena Maria Hilgenkamp, Elizabeth Cornellia Schroeder, Sang Ouk Wee, Georgios Grigoriadis, Alexander Jacob Rosenberg, Tracy Baynard, Bo Fernhall
Physical Therapy Faculty Research
Background: Individuals with Down Syndrome (DS) have autonomic dysfunction impacting regulation of heart rate, Blood Pressure (BP), and peripheral vasoconstriction. This may alter central hemodynamics through different wave reflections. We investigated central hemodynamics including wave reflection during rest and a sympathoexcitatory stimulus [Lower Body Negative Pressure (LBNP)] in individuals with DS and controls. Methods: Radial applanation tonometry was performed on participants with and without DS before and during 5-min LBNP stimulus of −20 mmHg. Waveforms were calibrated to mean and diastolic BP. Generalized transfer function was used to estimate aortic pressures [Systolic Blood Pressure (aSBP), Diastolic Blood Pressure (aDBP), mean …
Electrochemical Hydrogen Evolution Over Hydrothermally Synthesized Re-Doped Mos2 Flower-Like Microspheres, Juan Aliaga, Pablo Vera, Juan Araya, Luis Ballesteros, Julio Urzúa, Mario Farías, Francisco Paraguay-Delgado, Gabriel Alonso-Núñez, Guillermo González, Eglantina Benavente
Electrochemical Hydrogen Evolution Over Hydrothermally Synthesized Re-Doped Mos2 Flower-Like Microspheres, Juan Aliaga, Pablo Vera, Juan Araya, Luis Ballesteros, Julio Urzúa, Mario Farías, Francisco Paraguay-Delgado, Gabriel Alonso-Núñez, Guillermo González, Eglantina Benavente
Faculty, Staff and Students Publications
In this research, we report a simple hydrothermal synthesis to prepare rhenium (Re)- doped MoS2 flower-like microspheres and the tuning of their structural, electronic, and electrocatalytic properties by modulating the insertion of Re. The obtained compounds were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Structural, morphological, and chemical analyses confirmed the synthesis of poorly crystalline Re-doped MoS2 flower-like microspheres composed of few stacked layers. They exhibit enhanced hydrogen evolution reaction (HER) performance with low overpotential of 210 mV at current density of 10 mA/cm2, with a …
Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen
Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Qingnan Liang, Rachayata Dharmat, Leah Owen, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen
Faculty, Staff and Students Publications
Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …
Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly
Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly
UNLV Theses, Dissertations, Professional Papers, and Capstones
Evolutionary outcomes are demonstrated by traits that affect an organism’s schedule of reproduction and survival. These life history traits are reflected in an organism’s physiology, development and behavior. Environmental changes, such as availability of nutritional resources, can profoundly affect evolutionary outcomes of individuals and populations. When shortages arise, there will be trade-offs in the allocation of resources, where one trait prevails at the expense of another.
In the laboratory, we can mimic conditions in nature and study the specific effects of the conditions that we re-create. In our case, over 100 generations of Drosophila melanogaster have been selected for starvation …
Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez
Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez
UNLV Theses, Dissertations, Professional Papers, and Capstones
Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …
Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken
Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken
Faculty, Staff and Students Publications
Sensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases are such genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. We expand luciferase multiplexing in post-lysis endpoint luciferase assays from two to six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. All six luciferase reporter units are stitched together into one plasmid facilitating delivery of all reporter units through a process we termed solotransfection, minimizing experimental errors. We engineer a multiplex hextuple luciferase assay to probe pathway fluxes through five …
Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert
Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …
Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel
Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel
Faculty, Staff and Students Publications
The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary Trace–Mutual information (ET-Mip), revealed residues and residue pairs that, when switched in the D2 receptor to the corresponding residues from 5-HT2A, altered ligand potency …
Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin
Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Vincent Villette, Mariya Chavarha, Ivan K Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin
Faculty, Staff and Students Publications
Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …
Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey
Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey
Department of Cancer Biology Faculty Papers
The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …
Langerhans Cells Orchestrate The Protective Antiviral Innate Immune Response In The Lymph Node., Eric B. Wong, Brian Montoya, Colby Stotesbury, Maria Ferez, Ren-Huan Xu, Luis J. Sigal
Langerhans Cells Orchestrate The Protective Antiviral Innate Immune Response In The Lymph Node., Eric B. Wong, Brian Montoya, Colby Stotesbury, Maria Ferez, Ren-Huan Xu, Luis J. Sigal
Department of Microbiology and Immunology Faculty Papers
During disseminating viral infections, a swift innate immune response (IIR) in the draining lymph node (dLN) that restricts systemic viral spread is critical for optimal resistance to disease. However, it is unclear how this IIR is orchestrated. We show that after footpad infection of mice with ectromelia virus, dendritic cells (DCs) highly expressing major histocompatibility complex class II (MHC class IIhi DCs), including CD207+ epidermal Langerhans cells (LCs), CD103+CD207+ double-positive dermal DCs (DP-DCs), and CD103−CD207− double-negative dermal DCs (DN-DCs) migrate to the dLN from the skin carrying virus. MHC class IIhi …
Allele-Specific Rna Interference Prevents Neuropathy In Charcot-Marie-Tooth Disease Type 2d Mouse Models., Kathryn H Morelli, Laurie B Griffin, Nettie K Pyne, Lindsay M Wallace, Allison M Fowler, Stephanie N Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O Kitzman, Samuel G Kocen, Timothy J Hines, Emily L Spaulding, James R Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q Harper, Robert W Burgess
Allele-Specific Rna Interference Prevents Neuropathy In Charcot-Marie-Tooth Disease Type 2d Mouse Models., Kathryn H Morelli, Laurie B Griffin, Nettie K Pyne, Lindsay M Wallace, Allison M Fowler, Stephanie N Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O Kitzman, Samuel G Kocen, Timothy J Hines, Emily L Spaulding, James R Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q Harper, Robert W Burgess
Department of Biochemistry and Molecular Biology Faculty Papers
Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases - where treatment may require reduction in the expression of a toxic mutant protein resulting from a gain-of-function allele - is unclear. Here we show the efficacy of allele-specific RNAi as a potential therapy for Charcot-Marie-Tooth disease type 2D (CMT2D), caused by dominant mutations in glycyl-tRNA synthetase (GARS). A de novo mutation in GARS was identified in a patient with a severe peripheral neuropathy, and a mouse model precisely recreating the mutation …
Sighting Acute Myocardial Infarction Through Platelet Gene Expression., Giuliana Gobbi, Cecilia Carubbi, Guidantonio Malagoli Tagliazucchi, Elena Masselli, Prisco Mirandola, Filippo Pigazzani, Antonio Crocamo, Maria Francesca Notarangelo, Sergio Suma, Elvezia Paraboschi, Giuseppe Maglietta, Srikanth Nagalla, Giulia Pozzi, Daniela Galli, Mauro Vaccarezza, Paolo Fortina, Sankar Addya, Adam Ertel, Paul Bray, Stefano Duga, Carlo Berzuini, Marco Vitale, Diego Ardissino
Sighting Acute Myocardial Infarction Through Platelet Gene Expression., Giuliana Gobbi, Cecilia Carubbi, Guidantonio Malagoli Tagliazucchi, Elena Masselli, Prisco Mirandola, Filippo Pigazzani, Antonio Crocamo, Maria Francesca Notarangelo, Sergio Suma, Elvezia Paraboschi, Giuseppe Maglietta, Srikanth Nagalla, Giulia Pozzi, Daniela Galli, Mauro Vaccarezza, Paolo Fortina, Sankar Addya, Adam Ertel, Paul Bray, Stefano Duga, Carlo Berzuini, Marco Vitale, Diego Ardissino
Department of Cancer Biology Faculty Papers
Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression …
Influence Of Metabolic Capacity On The Consequences Of Spreading Depolarization, Katelyn M. Reinhart
Influence Of Metabolic Capacity On The Consequences Of Spreading Depolarization, Katelyn M. Reinhart
Biomedical Sciences ETDs
In the United States, stroke is the fifth leading cause of death and stroke survivors often face long-term disability. After ischemic stroke, the ischemic territory can expand and recruit previously viable tissues into the lesioned area. During this critical period, there is an unsettling lack of interventions that prevent or treat secondary neuronal loss and cognitive decline. Clinical subdural recordings have revealed a close link between infarct progression and waves of spreading depolarizations (SD) in the acutely injured brain. SD is a slowly progressing wave of near-complete neuroglia depolarization that is extremely energetically demanding and this additional metabolic ‘hit’ …
Genetic Screening For Breast Cancer In The Primary Care Setting, Michael Nick Gomez
Genetic Screening For Breast Cancer In The Primary Care Setting, Michael Nick Gomez
Doctor of Nursing Practice
The purpose of this project was to increase adherence to the U.S. Preventive Services Task Force and National Comprehensive Cancer Network guidelines for breast cancer screening and genetic testing. Screening for breast cancer risk factors including genetic testing helps reduce the incidence of breast cancer. A protocol was developed based on national clinical guidelines to increase screening and genetic testing for breast cancer. Provider responsibilities included screening all patients 18 years of age and older for risks factors of breast cancer, referring patients with a significant risk based on the screening for genetic testing and providing referrals for genetic counseling …
The Dynamic Impacts Of Online Healthcare Community On Physician Altruism: A Hidden Markov Model, Kai Luo, Qiu-Hong Wang, Hock Hai Teo
The Dynamic Impacts Of Online Healthcare Community On Physician Altruism: A Hidden Markov Model, Kai Luo, Qiu-Hong Wang, Hock Hai Teo
Research Collection School Of Computing and Information Systems
Physician altruism is not only a key foundation of modern medical professionalism, but also a critical component in the theoretical health economics study. There is considerable interest in understanding the impacts of contemporary healthcare technology on physician altruism. In this paper, we investigate the dynamic influence of multiple incentive mechanisms developed by an online healthcare community (OHC) on physician altruism. We model physician altruism as the degree of tendency to benefit the patients at the cost of oneself and focus on the incentive mechanisms that give physicians social and economic returns. The dynamics of physician altruism is characterized via a …
Examining The Theoretical Mechanisms Underlying Health Information Exchange Impact On Healthcare Outcomes: A Physician Agency Perspective, Fang Zhou, Qiu-Hong Wang, Hock Hai Teo
Examining The Theoretical Mechanisms Underlying Health Information Exchange Impact On Healthcare Outcomes: A Physician Agency Perspective, Fang Zhou, Qiu-Hong Wang, Hock Hai Teo
Research Collection School Of Computing and Information Systems
Health information exchange (HIE) is presumed to reduce medical costs by facilitating information sharing across healthcare providers. Existing studies focused on different medical costs or one set of costs, and resulted in mixed findings. We examine the effects of patient access to HIE on two of the most important medical costs of a hospitalization episode - test costs and medication costs - through a natural experiment and the discharge data of a hospital. Besides the negative direct effect of access to HIT on tests costs, we also find its positive spillover effect on medication costs, such that more patients having …
Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang
Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang
Faculty, Staff and Students Publications
Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously …
Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos
Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos
Faculty, Staff and Students Publications
BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.
METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml …
Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch
Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch
Faculty, Staff and Students Publications
Patellar instability is a debilitating condition, and trauma due to the dislocations may severely damage the articular cartilage of the patellofemoral joint. The lack of healing capacity of cartilage makes treatment of such lesions challenging. In young patients, preservation of native bone and cartilage is a priority, and therefore arthroplasty procedures should be avoided even in relatively larger lesions. Fresh osteochondral allografting has been described for these difficult and complex cases, with recent studies showing promising results. In this surgical technique, we describe the use of bipolar osteochondral allografts of the patella and trochlea and patellofemoral joint reconstruction for large …