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The Use Of Probiotics To Prevent Ventilator-Associated Pneumonia In Adults, Michael Roper, Paige Douthett Dec 2019

The Use Of Probiotics To Prevent Ventilator-Associated Pneumonia In Adults, Michael Roper, Paige Douthett

Physician Assistant Capstones, 2016 to 2019

Objective: To assess the efficacy and safety of preventing the acquisition of ventilator- associated pneumonia with the use of probiotic supplementation, as compared to a placebo, among hospitalized adult men and women receiving more than 24 hours of mechanical ventilation. Design: Systematic Literature Review. Methods: Systematic searches were conducted through PubMed and Scopus using the search terms “ventilator”, “probiotics”, and “prevention”. Records were excluded from the analysis if they were published before 2015, full text was not available, studies other than randomized control trial or cohort studies, and if the study population was less than 18 years old. Results: Of …


Iris Metastasis As The Initial Presentation Of Upper Gastrointestinal Tract Carcinoma: A Case Report, M A Rehman Siddiqui, Syed Zohaib Maroof Hussain, Muhammed Mubarak Dec 2019

Iris Metastasis As The Initial Presentation Of Upper Gastrointestinal Tract Carcinoma: A Case Report, M A Rehman Siddiqui, Syed Zohaib Maroof Hussain, Muhammed Mubarak

Section of Ophthalmology

Background: We report a case of a patient with iris metastasis as the initial manifestation of a systemic cancer: upper gastrointestinal tract carcinoma.
Case presentation: A 24-year-old Asian man presented to our hospital with complaints of red left eye, decreased visual acuity, pain, and photophobia for about 3 weeks with no prior history of cancer or any other medical abnormality. Ocular examination showed a pinkish white lesion on the superonasal part of the iris. The patient's intraocular pressure was progressively increasing despite medications, followed by lymphadenopathy 4 weeks later. Comprehensive examination was performed along with a complete systemic workup, which …


Disaggregated Hispanic Groups And Cancer: Importance, Methodology, And Current Knowledge, Paulo S. Pinheiro, Karen E. Callahan, Erin N. Kobetz Dec 2019

Disaggregated Hispanic Groups And Cancer: Importance, Methodology, And Current Knowledge, Paulo S. Pinheiro, Karen E. Callahan, Erin N. Kobetz

Environmental & Global Health Faculty Research

Cancer is the leading cause of death among Latinos/Hispanics, the largest racial/ethnic minority group in the United States. Their cancer burden has nearly doubled in 15 years, with 129,000 new cancer cases nationwide in 2014. As this relatively young Hispanic population ages, this burden will inevitably increase; thus, accurate characterization of the Hispanic cancer experience is critical. In this chapter, we summarize the current knowledge on cancer in Hispanics, with a focus on the imperative of disaggregating by specific Hispanic group (Mexicans, Puerto Ricans, Cubans, Central Americans, South Americans, and Dominicans) and nativity. We also describe for the first time …


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 Dec 2019

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 …


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 Dec 2019

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 …


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 Dec 2019

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 Dec 2019

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 …


Unraveling Complexity About Childhood Obesity And Nutritional Interventions: Modeling Interactions Among Psychological Factors., Keith Feldman, Gisela M B Solymos, Maria Paula De Albuquerque, Nitesh V. Chawla Dec 2019

Unraveling Complexity About Childhood Obesity And Nutritional Interventions: Modeling Interactions Among Psychological Factors., Keith Feldman, Gisela M B Solymos, Maria Paula De Albuquerque, Nitesh V. Chawla

Manuscripts, Articles, Book Chapters and Other Papers

As the global prevalence of childhood obesity continues to rise, researchers and clinicians have sought to develop more effective and personalized intervention techniques. In doing so, obesity interventions have expanded beyond the traditional context of nutrition to address several facets of a child's life, including their psychological state. While the consideration of psychological features has significantly advanced the view of obesity as a holistic condition, attempts to associate such features with outcomes of treatment have been inconclusive. We posit that such uncertainty may arise from the univariate manner in which features are evaluated, focusing on a particular aspect such as …


Fingolimod Plays Role In Attenuation Of Myocardial Injury Related To Experimental Model Of Cardiac Arrest And Extracorporeal Life Support Resuscitation, Naseer Ahmed, Abid Laghari, Bashar Albkhoor, Sobia Tabassum, Sultan Ayoub Meo, Nazeer Muhammad, Daniele Linardi, Abeer A. Al-Masri, Guido Fumagalli, Giovanni Battista Luciani, Giuseppe Faggian, Alessio Rungatscher Dec 2019

Fingolimod Plays Role In Attenuation Of Myocardial Injury Related To Experimental Model Of Cardiac Arrest And Extracorporeal Life Support Resuscitation, Naseer Ahmed, Abid Laghari, Bashar Albkhoor, Sobia Tabassum, Sultan Ayoub Meo, Nazeer Muhammad, Daniele Linardi, Abeer A. Al-Masri, Guido Fumagalli, Giovanni Battista Luciani, Giuseppe Faggian, Alessio Rungatscher

Department of Biological & Biomedical Sciences

Background: Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia-reperfusion injury is a leading cause of myocardial dysfunction. The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Aim of the study was to investigate the cardioprotective role of fingolimod in an in vivo model of cardiac arrest and resuscitation.
Methods: In this study, an in vivo rat model of cardiac arrest using extracorporeal membrane oxygenation resuscitation monitored by invasive hemodynamic measurement was developed. At the beginning of extracorporeal life support (ECLS), animals were randomly treated …


Metastatic Melanoma Of The Gallbladder Presenting As Polyp In Acute Cholecystitis., Nirvana B Saraswat, William B Devoe Dec 2019

Metastatic Melanoma Of The Gallbladder Presenting As Polyp In Acute Cholecystitis., Nirvana B Saraswat, William B Devoe

Oncology Articles

Malignant melanoma is an aggressive neural crest cell-derived neoplasm with a propensity for metastasis to almost any organ. Gastrointestinal metastasis may manifest as gallbladder polyps. We report a case of metastatic malignant melanoma diagnosed in an 81-year-old male after cholecystectomy performed for acute cholecystitis. Cholecystectomy remains the standard of care for treatment of isolated gallbladder metastasis, especially in the setting of symptomatic disease. Mutation-directed chemotherapeutic and immunotherapeutic modalities serve as efficacious adjunctive therapy in addition to primary surgical resection for this rare condition.


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 Dec 2019

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 …


Optimizing Cancer Cure Dialog: An Analysis Of Pancreatic Cancer Patients' Views Regarding Survival And Cure., Avinoam Nevler, Scott W. Keith, Harish Lavu, Theresa P. Yeo, Shawnna Cannaday, Charles J. Yeo, Jordan M. Winter Dec 2019

Optimizing Cancer Cure Dialog: An Analysis Of Pancreatic Cancer Patients' Views Regarding Survival And Cure., Avinoam Nevler, Scott W. Keith, Harish Lavu, Theresa P. Yeo, Shawnna Cannaday, Charles J. Yeo, Jordan M. Winter

Department of Surgery Faculty Papers

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. Clinicians commonly refer to surgical therapy as resection with curative intent. However, PDA cure rates after resection remain unknown and the definition of cure remains vague. We investigated how patients (the majority undergoing resection), family members, and clinicians understand the concept of cure, to better inform discussions with patients regarding PDA prognosis.

METHODS: In a prospective survey, cohorts were asked to indicate the best definition of cure from three choices: 5-year survival endpoint (typically used in the literature), a biological endpoint without biochemical or radiographic signs of disease (similar to …


Postpartum Endometritis And Infection Following Incomplete Or Complete Abortion: Case Definition & Guidelines For Data Collection, Analysis, And Presentation Of Maternal Immunization Safety Data, C E. Rouse, L O. Eckert, F M. Muñoz, J S A. Stringer, S Kochhar, L Bartlett, M Sanicas, D J. Dudley, D M. Harper, Fyezah Jehan Dec 2019

Postpartum Endometritis And Infection Following Incomplete Or Complete Abortion: Case Definition & Guidelines For Data Collection, Analysis, And Presentation Of Maternal Immunization Safety Data, C E. Rouse, L O. Eckert, F M. Muñoz, J S A. Stringer, S Kochhar, L Bartlett, M Sanicas, D J. Dudley, D M. Harper, Fyezah Jehan

Department of Paediatrics and Child Health

Abstract are not provided by the author/publisher


Examining The Relationship Of Exercise And Sleep In Students Across Multiple Academic Disciplines, Taylor Zewe Dec 2019

Examining The Relationship Of Exercise And Sleep In Students Across Multiple Academic Disciplines, Taylor Zewe

Honors Projects

Students in college learn the importance of balancing their academic studies with their sleep and exercise habits. The amount of sleep and exercise a student recieves has been examined in previous research studies. In these studies it was found that exercise had a postive affect on the amount of sleep received. However, there is little research on the affect academic discipline has on sleep habits and/or exercise habits of students in college. The purpose of this study is to examine the sleep and exercise habits among students in multiple academic majors at Bowling Green State University.


In Vivo Investigation Of The Tissue Response To Commercial Teflon Insulin Infusion Sets In Large Swine For 14 Days: The Effect Of Angle Of Insertion On Tissue Histology And Insulin Spread Within The Subcutaneous Tissue., Gabriella Eisler, Jasmin R. Kastner, Marc C. Torjman, Abdurizzagh Khalf, David Diaz, Alek R. Dinesen, Channy Loeum, Mathew L. Thakur, Paul Strasma, Jeffrey I. Joseph Dec 2019

In Vivo Investigation Of The Tissue Response To Commercial Teflon Insulin Infusion Sets In Large Swine For 14 Days: The Effect Of Angle Of Insertion On Tissue Histology And Insulin Spread Within The Subcutaneous Tissue., Gabriella Eisler, Jasmin R. Kastner, Marc C. Torjman, Abdurizzagh Khalf, David Diaz, Alek R. Dinesen, Channy Loeum, Mathew L. Thakur, Paul Strasma, Jeffrey I. Joseph

Department of Anesthesiology Faculty Papers

Objective: This study investigated the effects of the inflammatory tissue response (ITR) to an insulin infusion set (IIS) on insulin bolus spread over wear time, as well as the effect of cannula insertion angle on the ITR, bolus shape, and pump tubing pressure.

Research design and methods: Angled or straight IISs were inserted every other day for 14 days into the subcutaneous tissue of 11 swine and insulin was delivered continuously. Prior to euthanasia, a 70 µL bolus of insulin/X-ray contrast agent was infused while recording a pressure profile (peak tubing pressure, pmax; area under the pressure curve, …


Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh Dec 2019

Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh

Pharmacy and Wellness Review

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness …


Memantine: Can It Be Used To Treat Children With Autism Spectrum Disorder?, Austin Brown, Katherine Liu, Pul Lee, Rachel Muhlenkamp, Manoranjan D'Souza Dec 2019

Memantine: Can It Be Used To Treat Children With Autism Spectrum Disorder?, Austin Brown, Katherine Liu, Pul Lee, Rachel Muhlenkamp, Manoranjan D'Souza

Pharmacy and Wellness Review

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social, behavior and communicative skills. The current therapy for ASD only targets the associated symptoms such as aggression, self-harming acts or temper tantrums but not the core symptoms of social dysfunction. The pathology of ASD is not fully understood. Interestingly, imaging studies in ASD patients have reported abnormal high levels of glutamate in certain brain regions that play an important role in social interaction and communication. Thus, it has been hypothesized that medications attenuating glutamate transmission may be used as treatment for some of the core symptoms of …


Marijuana And Its Cardiovascular Implications, Albert Bui, Daniel Powell, Victoria Cho, Kelsey Lindsley, Lindsey Peters Dec 2019

Marijuana And Its Cardiovascular Implications, Albert Bui, Daniel Powell, Victoria Cho, Kelsey Lindsley, Lindsey Peters

Pharmacy and Wellness Review

As marijuana becomes legalized for medical use, it is important for prescribers and pharmacists to be knowledgeable about the important aspects of marijuana such as mechanism of action, indications and abuse potential. Although marijuana's medicinal benefits are frequently reported, the risks, namely cardiovascular risks, associated with its utilization are often overlooked. Use of marijuana has been reported to increase the risk of myocardial infarction, tachycardia and hypotension, among others. Health care providers must determine if marijuana's benefits outweigh such risks when marijuana therapy is an option. It is also important for pharmacists to understand how to successfully counsel patients using …


Single Versus Multi-Center Surgeons' Risk-Adjusted Mitral Valve Repair Procedural Outcomes, Anne Bennett, Thomas Bogue, Samuel Greenberg, Joshua Zhu, Samantha Novotny, Joseph Pizzuti, Lee A. Santore, Robert H. Habib, Annie Laurie Laurie Shroyer, Jonathan Price, Henry Tannous, Thomas Bilfinger Dec 2019

Single Versus Multi-Center Surgeons' Risk-Adjusted Mitral Valve Repair Procedural Outcomes, Anne Bennett, Thomas Bogue, Samuel Greenberg, Joshua Zhu, Samantha Novotny, Joseph Pizzuti, Lee A. Santore, Robert H. Habib, Annie Laurie Laurie Shroyer, Jonathan Price, Henry Tannous, Thomas Bilfinger

Department of Surgery Faculty Publications

The purpose of this study is to explore strategies to improve mitral valve repair (MVr) outcomes. This research explores postoperative outcomes of patients undergoing MVr surgery by single center surgeons versus patients of multicenter surgeons. Specific outcomes of interest include 30-day operative mortality, major operative complications (e.g., deep sternal wound infection, permanent stroke, renal dysfunction requiring dialysis, reoperation, and prolonged ventilation), length of stay, and 30-day readmissions.

In brief, the serisk-adjusted outcome rates for surgeons that perform mitral valve repair procedures will be compared for surgeons that operate at a single center [i.e. SC surgeons] versus multiple centers [i.e. MC …


Image Restoration Using Automatic Damaged Regions Detection And Machine Learning-Based Inpainting Technique, Chloe Martin-King Dec 2019

Image Restoration Using Automatic Damaged Regions Detection And Machine Learning-Based Inpainting Technique, Chloe Martin-King

Computational and Data Sciences (PhD) Dissertations

In this dissertation we propose two novel image restoration schemes. The first pertains to automatic detection of damaged regions in old photographs and digital images of cracked paintings. In cases when inpainting mask generation cannot be completely automatic, our detection algorithm facilitates precise mask creation, particularly useful for images containing damage that is tedious to annotate or difficult to geometrically define. The main contribution of this dissertation is the development and utilization of a new inpainting technique, region hiding, to repair a single image by training a convolutional neural network on various transformations of that image. Region hiding is also …


The Black Identity, Hair Product Use, And Breast Cancer Scale, Dede Teteh, Marissa Ericson, Sabine Monice, Lenna Dawkins-Moultin, Nasim Bahadorani, Phyllis Clark, Eudora Mitchell, Lindsey S. Treviño, Adana Llanos, Rick Kittles, Susanne Montgomery Dec 2019

The Black Identity, Hair Product Use, And Breast Cancer Scale, Dede Teteh, Marissa Ericson, Sabine Monice, Lenna Dawkins-Moultin, Nasim Bahadorani, Phyllis Clark, Eudora Mitchell, Lindsey S. Treviño, Adana Llanos, Rick Kittles, Susanne Montgomery

Health Sciences and Kinesiology Faculty Articles

Introduction
Across the African Diaspora, hair is synonymous with identity. As such, Black women use a variety of hair products, which often contain more endocrine-disrupting chemicals than products used by women of other races. An emerging body of research is linking chemicals in hair products to breast cancer, but there is no validated instrument that measures constructs related to hair, identity, and breast health. The objective of this study was to develop and validate the Black Identity, Hair Product Use, and Breast Cancer Scale (BHBS) in a diverse sample of Black women to measure the social and cultural constructs associated …


Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez Dec 2019

Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez

Articles, Abstracts, and Reports

BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction …


Update To The Vitamin C, Thiamine And Steroids In Sepsis (Victas) Protocol: Statistical Analysis Plan For A Prospective, Multicenter, Double-Blind, Adaptive Sample Size, Randomized, Placebo-Controlled, Clinical Trial., Christopher J. Lindsell, Anna Mcglothlin, Samuel Nwosu, Todd W. Rice, Alex Hall, Gordon R. Bernard, Laurence W. Busse, E. Wesley Ely, Alpha A. Fowler, David F. Gaieski, Jeremiah S. Hinson, Michael H. Hooper, James C. Jackson, Gabor D. Kelen, Mark Levine, Greg S. Martin, Richard E. Rothman, Jonathan E. Sevransky, Kert Viele, David W. Wright, David N. Hager Dec 2019

Update To The Vitamin C, Thiamine And Steroids In Sepsis (Victas) Protocol: Statistical Analysis Plan For A Prospective, Multicenter, Double-Blind, Adaptive Sample Size, Randomized, Placebo-Controlled, Clinical Trial., Christopher J. Lindsell, Anna Mcglothlin, Samuel Nwosu, Todd W. Rice, Alex Hall, Gordon R. Bernard, Laurence W. Busse, E. Wesley Ely, Alpha A. Fowler, David F. Gaieski, Jeremiah S. Hinson, Michael H. Hooper, James C. Jackson, Gabor D. Kelen, Mark Levine, Greg S. Martin, Richard E. Rothman, Jonathan E. Sevransky, Kert Viele, David W. Wright, David N. Hager

Department of Emergency Medicine Faculty Papers

BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock.

METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. …


Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez Dec 2019

Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez

Articles, Abstracts, and Reports

BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction …


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast Dec 2019

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …


Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito Dec 2019

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …


Fracture Repair Requires Trka Signaling By Skeletal Sensory Nerves., Zhu Li, Carolyn A Meyers, Leslie Chang, Seungyong Lee, Zhi Li, Ryan Tomlinson, Ahmet Hoke, Thomas L Clemens, Aaron W James Dec 2019

Fracture Repair Requires Trka Signaling By Skeletal Sensory Nerves., Zhu Li, Carolyn A Meyers, Leslie Chang, Seungyong Lee, Zhi Li, Ryan Tomlinson, Ahmet Hoke, Thomas L Clemens, Aaron W James

Department of Orthopaedic Surgery Faculty Papers

Bone is richly innervated by nerve growth factor-responsive (NGF-responsive) tropomyosin receptor kinase A-expressing (TrKa-expressing) sensory nerve fibers, which are required for osteochondral progenitor expansion during mammalian skeletal development. Aside from pain sensation, little is known regarding the role of sensory innervation in bone repair. Here, we characterized the reinnervation of tissue following experimental ulnar stress fracture and assessed the impact of loss of TrkA signaling in this process. Sequential histological data obtained in reporter mice subjected to fracture demonstrated a marked upregulation of NGF expression in periosteal stromal progenitors and fracture-associated macrophages. Sprouting and arborization of CGRP+TrkA+ sensory nerve fibers …


Cardiovascular Risk In Patients With Rheumatoid Arthritis: The Role Of Cholesterylester Transfer Protein, Ali M. Mursi, Emad M. Elshebiny, Lobna Y. Ebrahim, Sahar H. Quashwa, Sherry K. Abdelrahman, Taghreed F. Mohammed Mostafa Dec 2019

Cardiovascular Risk In Patients With Rheumatoid Arthritis: The Role Of Cholesterylester Transfer Protein, Ali M. Mursi, Emad M. Elshebiny, Lobna Y. Ebrahim, Sahar H. Quashwa, Sherry K. Abdelrahman, Taghreed F. Mohammed Mostafa

Journal of Medicine in Scientific Research

Aim To detect serum level of cholesterylester transfer protein (CETP) (the enzyme involved in reverse cholesterol transport) in patients with rheumatoid arthritis (RA) and to evaluate its relation to various clinical parameters of the disease, lipid profile, and carotid intima-media thickness (CIMT) as a marker of atherosclerosis and cardiovascular disease risk. Patients and methods This study involved a total of 80 participants, comprising 50 patients with RA and 30 age-matched and sex-matched healthy controls. Detailed medical history and thorough clinical examination (general and musculoskeletal) as well as laboratory investigations including lipid profile were performed for all patients with RA. Serum …


The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan Dec 2019

The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan

Electronic Theses and Dissertations

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …


A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response To Obeticholic Acid In Patients With Nash., Samer Gawrieh, Xiuqing Guo, Jingyi Tan, Marie Lauzon, Kent D Taylor, Rohit Loomba, Oscar W Cummings, Sreekumar Pillai, Pallav Bhatnagar, Kris V Kowdley, Katherine Yates, Laura A Wilson, Yii-Der Ida Chen, Jerome I Rotter, Naga Chalasani Dec 2019

A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response To Obeticholic Acid In Patients With Nash., Samer Gawrieh, Xiuqing Guo, Jingyi Tan, Marie Lauzon, Kent D Taylor, Rohit Loomba, Oscar W Cummings, Sreekumar Pillai, Pallav Bhatnagar, Kris V Kowdley, Katherine Yates, Laura A Wilson, Yii-Der Ida Chen, Jerome I Rotter, Naga Chalasani

Articles, Abstracts, and Reports

A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome-wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 …