Digital Commons Network^™

A Rare Heterozygous Trem2 Coding Variant Identified In Familial Clustering Of Dementia Affects An Intrinsically Disordered Protein Region And Function Of Trem2, M Karsak, K Glebov, M Scheffold, T Bajaj, A Kawalia, I Karaca, S Rading, J Kornhuber, O Peters, M Diez‐Fairen, L Frölich, M Hüll, J Wiltfang, M Scherer, S Riedel‐Heller, A Schneider, Mt Heneka, K Fliessbach, A Sharaf, H Thiele, M Lennarz, F Jessen, W Maier, C Kubisch, Z Ignatova, P Nürnberg, P Pastor, J Walter, A Ramirez

Peninsula Medical School

No abstract provided.

Towards Real-Time Monitoring Of Bacterial Cultures Without The Need For Physical Sampling: Elastic Scattering, Fluorescence And Raman Spectroscopy Of Escherichia Coli Cultures., Richard Thomas Mcdonough

Dissertations - ALL

The first part of this dissertation pertains to the fringe analysis of a hydration layer that forms spontaneously when biofilms dry. This layer at optical thickness ˂ 20 µm is approximately 1-2 orders of magnitude thinner than the biofilm thickness as measured by confocal Raman microscopy and confocal fluorescent microscopy. Drying/rehydration experiments performed on films withstood multiple cycles, returning to the same optical thickness proving their robust nature. The strength of a distinct water peak (1451 nm) in addition to others, reflects the thickness of the hydration layer. Confocal Raman microscopy showed that biofilms are chemically very similar to pure …

Hope, Courage, And Resilience In The Lives Of Transgender Women Of Color, Nadine Ruff, Amy B. Smoyer, Jean Breny

The Qualitative Report

There is a lack of qualitative and strengths-based knowledge about the lived experience of transgender women of color in the US. To address this research gap, a Photovoice project was undertaken with five transgender women living in a small urban area. Thematic analysis of the participants’ discussion of their photographs identified three major themes: hope, courage, and resilience. Analysis suggests a framework for understanding these women’s lived experiences and the psychosocial tools that they use to negotiate their daily lives and persevere in the face of interpersonal and structural oppression.

Global Health Competencies In Uk Postgraduate Medical Training: A Scoping Review And Curricular Content Analysis, Nader Al-Shakarchi, Lucy Obolensky, Sarah Walpole, Harry Hemingway, Amitava Banerjee

Peninsula Medical School

ObjectiveTo assess global health (GH) training in all postgraduate medical education in the UK.DesignMixed methodology: scoping review and curricular content analysis using two GH competency frameworks.Setting and participantsA scoping review (until December 2017) was used to develop a framework of GH competencies for doctors. National postgraduate medical training curricula were analysed against this and a prior framework for GH competencies. The number of core competencies addressed and/or appearing in each programme was recorded.OutcomesThe scoping review identified eight relevant publications. A 16-competency framework was developed and, with a prior 5-competency framework, used to analyse each of 71 postgraduate medical curricula. Curricula …

A Mechanistic And Pathophysiological Approach For Stroke Associated With Drugs Of Abuse, Aristides Tsatsakis, Anca O. Docea, Daniela Calina, Konstantinos Tsarouhas, Laura-Maria Zamfira, Radu Mitrut, Javad Sharifi-Rad, Leda Kovatsi, Vasileios Siokas, Efthimios Dardiotis, Nikolaos Drakoulis, George Lazopoulos, Christina Tsitsimpikou, Panayiotis Mitsias, Monica Neagu

Neurology Articles

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas …

Pathobiome Driven Gut Inflammation In Pakistani Children With Environmental Enteric Dysfunction, Najeeha Talat Iqbal, Sana Syed, Furqan Kabir, Zehra Jamil, Tauseef Akhund, Shahida Qureshi, Jie Liu, Jennie Ma Z, Shan Guleria, Andrew Gewirtz, Christopher Duggan P, Molly Hughes A, Kamran Sadiq, Asad Ali

Department of Paediatrics and Child Health

Environmental Enteric Dysfunction (EED) is an acquired small intestinal inflammatory condition underlying high rates of stunting in children <5 years of age in low- and middle-income countries. Children with EED are known to have repeated exposures to enteropathogens and environmental toxins that leads to malabsorptive syndrome. We aimed to characterize association of linear growth faltering with enteropathogen burden and subsequent changes in EED biomarkers. In a longitudinal birth cohort (n = 272), monthly anthropometric measurements (Length for Age Z score- LAZ) of asymptomatic children were obtained up to 18 months. Biological samples were collected at 6 and 9 months for the assessment of biomarkers. A customized TaqMan array card was used to target 40 enteropathogens in fecal samples. Linear regression was applied to study the effect of specific enteropathogen infection on change in linear growth (ΔLAZ). Presence of any pathogen in fecal sample correlated with serum flagellin IgA (6 mo, r = 0.19, p = 0.002), fecal Reg 1b (6 mo, r = 0.16, p = 0.01; 9mo, r = 0.16, p = 0.008) and serum Reg 1b (6 mo, r = 0.26, p<0.0001; 9 mo, r = 0.15, p = 0.008). At 6 months, presence of Campylobacter [β (SE) 7751.2 (2608.5), p = 0.003] and ETEC LT [β (SE) 7089.2 (3015.04), p = 0.019] was associated with increase in MPO. Giardia was associated with increase in Reg1b [β (SE) 72.189 (26.394), p = 0.006] and antiflic IgA[β (SE) 0.054 (0.021), p = 0.0091]. Multiple enteropathogen infections in early life negatively correlated with ΔLAZ, and simultaneous changes in gut inflammatory and permeability markers. A combination vaccine targeting enteropathogens in early life could help in the prevention of future stunting

Our Envirome, Spring/Summer 2019, Issue 40

Sustain Magazine

No abstract provided.

Implementation Of Liver Cancer Education Among Health Care Providers And Community Coalitions In The Cherokee Nation, Behnoosh Momin, Jorge Mera, Whitney Essex, David Gahn, Margie Burkhart, Danielle Nielsen, Jennifer Mezzo, Alexander J Millman

Project ECHO Bibliography

INTRODUCTION: The Cherokee Nation Comprehensive Cancer Control Program collaborated with the Cherokee Nation Hepatitis C Virus (HCV) Elimination Program within Cherokee Nation's Health Services to plan and implement activities to increase knowledge and awareness of liver cancer prevention among health care providers and the Cherokee Nation community. From August 2017 to April 2018, the 2 programs implemented liver cancer prevention interventions that focused on education of health care providers and community members. We used descriptive statistics to analyze data collected from a brief, retrospective pre-post survey for each intervention. We assessed overall awareness and knowledge of liver cancer and ability …

Generation Of An Oncolytic Adenovirus Targeting The Cxcr4 And Cxcr7 Chemokine Receptors In Breast Cancer, Samia Melissa O'Bryan

LSU Doctoral Dissertations

Breast cancer is the most diagnosed cancer in women under 60 and the second most diagnosed cancer in women over 60. While treatments for localized breast cancer are quite successful with high survival rates at 99%, advanced breast cancer remains hard to treat with a nearly 75% decrease in survival. Current treatments are inefficient at treating advanced stages of breast cancer, and thus, new therapies are sorely needed to address the complexity of advanced stage breast cancer. The ideal therapy would be capable of systemic administration, targets cancer cells and spares normal tissue. Oncolytic adenovirus is an ideal therapeutic vector …

No Meaningful Drug Interactions With Doravirine, Lamivudine And Tenofovir Disoproxil Fumarate Co-Administration., Matt S. Anderson, Jocelyn Gilmartin, Li Fan, Ka Lai Yee, Walter K. Kraft, Ilias Triantafyllou, Christina Reitmann, Ying Guo, Rachael Liu, Marian Iwamoto

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration.

METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment …

Impacts Of Hiv Cure Interventions On Viral Reservoirs In Tissues, Paul W. Denton, Ole S. Søgaard, Martin Tolstrup

Biology Faculty Publications

HIV reservoirs persist in infected individuals despite combination antiretroviral therapy and can be identified in secondary lymphoid tissues, in intestinal tissues, in the central nervous system as well as in blood. Clinical trials have begun to explore effects of small molecule interventions to perturb the latent viral infection, but only limited information is available regarding the impacts of HIV cure-related clinical interventions on viral reservoirs found in tissues. Of the 14 HIV cure-related clinical trials since 2012 that have evaluated the effects of small molecule interventions in vivo, four trials have examined the impacts of the interventions in peripheral …

Are Microclimate Conditions In El Malpais National Monument Caves In New Mexico, Usa Suitable For Pseudogymnoascus Growth?, Terry J. Torres-Cruz, Andrea Porras-Alfaro, Nicole A. Caimi, Ogochukwu Nwabologu, Edward W. Strach, Kaitlyn J.H. Read, Jesse M. Young, Debbie C. Buecher, Diana E. Northup

International Journal of Speleology

White-nose syndrome (WNS) is a bat disease caused by the fungal pathogen Pseudogymnoascus destructans, which thrives in cold and very humid environments where bats frequently hibernate. Conidia of Pseudogymnoascus species are often documented on bats prior to the onset of WNS, but characterization of high-risk areas defined by microclimate cave conditions have been lacking. Investigating the occurrence of this fungal genus and appropriate environmental conditions to support P. destructans in southwestern U.S. caves is key to understanding the sites most likely to be impacted by WNS. Microclimate conditions in ten caves at El Malpais (ELMA) National Monument in New …

Using Machine Learning For Antimicrobial Resistant Dna Identification, Jason I. Lingle, John Santerre

SMU Data Science Review

In this paper, we present a novel machine learning-based methodology for identifying bacteria DNA sub-sequences that are associated with antimicrobial resistance. The dramatic rise in cases of antibiotic resistant bacteria has been an increasing threat across the globe as the existing treatments are rendered ineffective in treating most of these cases due to mutations of their DNA. Among the most recent bacteria to display antimicrobial resistance (AMR) is Neisseria Gonorrhea with the first global treatment failure taking place in 2016. In 2018, new cases of resistance to multiple, high levels of antibiotics were reported in the United Kingdom and Australia. …

Mucosal Infection Rewires Tnfɑ Signaling Dynamics To Skew Susceptibility To Recurrence, Lu Yu, Valerie P. O'Brien, Jonathan Livny, Denise Dorsey, Nirmalya Bandyopadhyay, Marco Colonna, Michael G. Caparon, Elisha D.O. Roberson, Scott J. Hultgren, Thomas Hannan

Open Access Publications

A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice …

Polio: From Eradication To Systematic, Sustained Control, Oliver Razum, Devi Sridhar, Albrecht Jahn, Shehla Zaidi, Gorik Ooms, Olaf Müller

Community Health Sciences

No abstract provided.

First-In-Human Study Of Tk-Positive Oncolytic Vaccinia Virus Delivered By Adipose Stromal Vascular Fraction Cells., Boris R Minev, Elliot Lander, John F Feller, Mark Berman, Bernadette M Greenwood, Ivelina Minev, Antonio F Santidrian, Duong Nguyen, Dobrin Draganov, Mehmet O Killinc, Anna Vyalkova, Santosh Kesari, Edward Mcclay, Gabriel Carabulea, Francesco M Marincola, Lisa H Butterfield, Aladar A Szalay

Articles, Abstracts, and Reports

BACKGROUND: ACAM2000, a thymidine kinase (TK)-positive strain of vaccinia virus, is the current smallpox vaccine in the US. Preclinical testing demonstrated potent oncolytic activity of ACAM2000 against several tumor types. This Phase I clinical trial of ACAM2000 delivered by autologous adipose stromal vascular fraction (SVF) cells was conducted to determine the safety and feasibility of such a treatment in patients with advanced solid tumors or acute myeloid leukemia (AML).

METHODS: Twenty-four patients with solid tumors and two patients with AML participated in this open-label, non-randomized dose-escalation trial. All patients were treated with SVF derived from autologous fat and incubated for …

Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo

School of Medicine Faculty Publications

The human neurotropic virus JCPyV, a member of the family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the …

Career Corner: Alumni, Friends To Network With Stemstart Freshmen, Ohio University College Of Arts & Sciences

All Forum Articles

No abstract provided.

Application Of New Technology For The Diagnosis Of Viral Infection, Jayme Parker

Biological Sciences

New technology is challenging conventional methods for characterizing pathogenic viruses in clinical laboratories. These newer methods are superior to older methods due to their ability to broadly target numerous pathogens in multiplexed ways. Even more intriguing, new technologies are capable of detecting viruses in non-targeted manners. Before these newer methods can be adopted by accredited medical laboratories, they must be validated to assess whether or not they meet minimum federal standards in terms of assay accuracy, precision, reproducibility, and cross-reactivity. This thesis begins to answer important questions facing clinical laboratories when adopting new technology. In Chapter 1, assays targeting single …

Evaluating The Effects Of Sanitizing Drinker Lines In Commercial Broiler Houses On The Water Quality And Microbial Content In Biofilm Layers, Kennedi Achilles

Electronic Theses and Dissertations

The importance of water quality and its ability to cause major impacts, whether it is positive or negative, is often overlooked in the poultry industry. The microbial content of water is just one of many water characteristics that need to be monitored and regulated to ensure a flock is receiving good quality water. A field study was conducted to determine the effects of four different sanitizers under commercial broiler house conditions, with three replications over a three flock period. Each flock was grown for 56 days with a 2 week period between each flock. Four oxidative sanitizers were used and …

Characterization Of Acute Tlr-7 Agonist-Induced Hemorrhagic Myocarditis In Mice By Multiparametric Quantitative Cardiac Magnetic Resonance Imaging., Nicoleta Baxan, Angelos Papanikolaou, Isabelle Salles-Crawley, Amrit Lota, Rasheda Chowdhury, Olivier Dubois, Jane Branca, Muneer G. Hasham, Nadia Rosenthal, Sanjay K Prasad, Lan Zhao, Sian E Harding, Susanne Sattler

Faculty Research 2019

Hemorrhagic myocarditis is a potentially fatal complication of excessive levels of systemic inflammation. It has been reported in viral infection, but is also possible in systemic autoimmunity. Epicutaneous treatment of mice with the Toll-like receptor 7 (TLR-7) agonist Resiquimod induces auto-antibodies and systemic tissue damage, including in the heart, and is used as an inducible mouse model of systemic lupus erythematosus (SLE). Here, we show that overactivation of the TLR-7 pathway of viral recognition by Resiquimod treatment of CFN mice induces severe thrombocytopenia and internal bleeding, which manifests most prominently as hemorrhagic myocarditis. We optimized a cardiac magnetic resonance (CMR) …

Automated Small-Scale Plant Imaging System, Sylvia Tan, James J. Potter

Mechanical Engineering and Materials Science Independent Study

For research laboratories, the use of commercial plant phenotyping systems is costly and often do not meet the requirements of the research project. As such, a small-scale plant imaging systems was developed for a biology research group at Washington University in St. Louis. A previous iteration of the device had been prototyped; however, several design requirements were not met, or were not mechanically efficient. Therefore, this paper proposes a second design consisting of a new bridge, trolley and canopy that can be transported easily by the user, and can be made with commercially available parts.

Computed Tomography Shows High Fracture Prevalence Among Physically Active Forager-Horticulturalists With High Fertility, Jonathan Stieglitz, Benjamin C. Trumble, Horus Study Team, Caleb E. Finch, Dong Li, Matthew J. Budoff, Hillard Kaplan, Michael D. Gurven

ESI Publications

Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here, we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on inactivity to explain skeletal fragility. Minimal BMD differences exist between Tsimane and American men, suggesting that systemic factors other than fertility (e.g. diet) do not …

Visualization Of Global Opioid Use Disorder Rates Based On Harm Reduction Availability, Soyol Enkh-Amgalan

The Journal of Purdue Undergraduate Research

No abstract provided.

Graduate Catalog 2019-2020, Southwestern Oklahoma State University

Graduate Catalogs

No abstract provided.

Equine Or Porcine Synovial Fluid As A Novel Ex Vivo Model For The Study Of Bacterial Free-Floating Biofilms That Form In Human Joint Infections, Jessica M. Gilbertie, Lauren V. Schnabel, Noreen J. Hickok, Megan E. Jacob, Brian P. Conlon, Irving Shapiro, Javad Parvizi, Thomas P. Schaer

Department of Orthopaedic Surgery Faculty Papers

Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such …

Comparison Of The Efficacy Of Four Drug Combinations For Immobilization Of Wild Pigs, Christine K. Ellis, Morgan E. Wehtje, Lisa L. Wolfe, Peregrine L. Wolff, Clayton D. Hilton, Mark C. Fisher, Shari Green, Michael P. Glow, Joeseph M. Halseth, Michael J. Lavelle, Nathan P. Snow, Eric H. Vannatta, Jack C. Rhyan, Kurt C. Vercauteren, William R. Lance, Pauline Nol

United States Department of Agriculture Wildlife Services: Staff Publications

Field immobilization of native or invasive wild pigs (Sus scrofa) is challenging. Drug combinations commonly used often result in unsatisfactory immobilization, poor recovery, and adverse side effects, leading to unsafe handling conditions for both animals and humans. We compared four chemical immobilization combinations, medetomidine–midazolam–butorphanol (MMB), butorphanol–azaperone–medetomidine (BAM™), nalbuphine–medetomidine–azaperone (NalMed-A), and tiletamine– zolazepam–xylazine (TZX), to determine which drug combinations might provide better chemical immobilization of wild pigs. We achieved adequate immobilization with no post-recovery morbidity withMMB. Adequate immobilization was achieved with BAM™; however, we observed post-recovery morbidity. Both MMB and BAM™ produced more optimal results relative to body temperature, recovery, and …

Elucidation Of The Role Of S100a8/A9 And Neutrophils In Chronic Tuberculosis, Ninecia Scott

Arts & Sciences Graduate Student Theses and Dissertations

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the number one killer due to a single infectious agent. Although, there is a vaccine against TB and antimicrobial treatments available, approximately 1.8 million people die each year. This underlines the importance of identifying and understanding mediators of TB pathogenesis to develop new diagnostics for early detection and therapies to treat individuals progressing to active disease. One of the cellular mediators that may play a role in TB pathogenesis are neutrophils. Neutrophils have been associated with active Tuberculosis (ATB); however, the role that neutrophils play within Mtb infection and disease is still …

Siderophore-Dependent Transport Paradigms For Iron Across The Bacterial Cell Envelope In The Human Pathogen Staphylococcus Aureus, Nathaniel Endicott

Arts & Sciences Graduate Student Theses and Dissertations

This work is focused on iron trafficking through ABC transporters in Staphylococcus aureus and combatting the growing antimicrobial resistance crisis by exploiting virulence factors as therapeutic targets. Specifically, the goal was to understand the role of a siderophore-binding lipoprotein FhuD2 in S. aureus iron trafficking. While S. aureus endogenously produces three metallophores for metal sequestration from the host, FhuD2 is thought to scavenge metals from hydroxamate-based xenosiderophores encountered in the host environment. FhuD2 is a critical virulence factor and vaccine candidate (Novartis) for MRSA. Since xenosiderophore scavenging systems are often dispensable, it was hypothesized that FhuD2 must be playing another …

Siderophore-Dependent Transport Paradigms For Iron Across The Bacterial Cell Envelope In The Human Pathogen Staphylococcus Aureus, Nathaniel Endicott

Arts & Sciences Graduate Student Theses and Dissertations

This work is focused on iron trafficking through ABC transporters in Staphylococcus aureus and combatting the growing antimicrobial resistance crisis by exploiting virulence factors as therapeutic targets. Specifically, the goal was to understand the role of a siderophore-binding lipoprotein FhuD2 in S. aureus iron trafficking. While S. aureus endogenously produces three metallophores for metal sequestration from the host, FhuD2 is thought to scavenge metals from hydroxamate-based xenosiderophores encountered in the host environment. FhuD2 is a critical virulence factor and vaccine candidate (Novartis) for MRSA. Since xenosiderophore scavenging systems are often dispensable, it was hypothesized that FhuD2 must be playing another …