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The Covid-19 Pandemic And On-Time Vaccine Completion In The Childhood Population: A Strategic Plan, Chris Elaine Mariano

UNLV Theses, Dissertations, Professional Papers, and Capstones

In March 2020, the entire world was placed into lockdown due to the COVID-19 virus, which impacted everyday life, including healthcare. People were scared to leave their homes and obtain preventative services, including vaccinations from birth to adulthood. There was a significant decrease in childhood vaccinations due to the COVID-19 pandemic. A strategy mix is defined as an intervention utilized for vaccination improvement. Strategy mixes were implemented to improve vaccination administration, and ultimately, vaccination rates. However, due to the COVID-19 pandemic, these strategy mixes or interventions were placed on hold causing immunization administration to decrease which could cause vaccine-preventable diseases …

“Back To The Jungle”: Investigating Rats, Grass, Scrub Typhus, And Plantations In Malaya, 1924–1974, Jack Greatrex

Research Collection College of Integrative Studies

In this article, I examine epidemiological research into scrub typhus in British Malaya between 1924 and 1974. Interwar research, I show, explained the incidence of the disease through conjunctions of rats, mites, plantations, lalang grass, and “jungle.” In the process, interwar researchers bridged a novel scientific vocabulary centering on disease “reservoirs” with older suspicions of plantations enabling “pests,” as well as with a later, explicitly ecological understanding of infectious disease. In exploring this history I thereby help to re-historicize the emergence of ecological notions of disease reservoirs, whilst also pushing at the limit-points of influential notions of “tropicality.”

The Addiction Treatment Experience Of Legally Mandated Opioid Users, Kaitlin E. Deitz

Theses, Dissertations and Culminating Projects

Clients who are legally mandated to addiction treatment for an opioid use disorder have high rates of treatment dropout, relapse, and recidivism. To gain a better understanding of the impact of treatment interventions on those measures, the author conducted a study to learn about the mandated treatment experience for opioid users from the clients’ perspectives using qualitative interviews. The first theme derived from the data was The Mandated Counselor-Client Relationship with subthemes of Cookie Cutter Counselor, Feeling Commodified, and Collusion. The second theme derived from the data was Necessary Conditions with subthemes of Feeling Cared for and Trust. The findings …

The Antioxidant Content Of Wong Lo Kat Tea, Valerie Kwong

Theses, Dissertations and Culminating Projects

Wong Lo Kat (or Wanglaoji in Mandarin) is a popular soft drink containing herbal tea that is often used as a Chinese folk remedy for mild ailments. The herbs included in the drink are the following: Chinese Mesona, White Frangipani, Microcos, Chrysanthemum, Japanese Honeysuckle, Heal All, and Chinese Licorice. While there is research on the individual plants, there is limited information on the combined mixture of the herbs included in the Wong Lo Kat drink, particularly in published English literature. Antioxidant content for the individual herbs and a combined mixture of equal parts of each herb was tested using the …

The Interconnected Roles Of Residues N189, E168, And S220 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase Catalysis, Erik Domlija

Theses, Dissertations and Culminating Projects

Tuberculosis (TB) is an infectious disease caused by the bacteria Mycobacterium tuberculosis that primarily attacks the lungs. Drug resistance for M. tuberculosis is emerging and therefore new drug targets need to be identified. One way to target TB is through the inhibition of the tryptophan biosynthetic pathway of M. tuberculosis since production of tryptophan is essential for the replication of M. tuberculosis. The enzyme Indole-3-glycerol phosphate synthase (MtIGPS) was chosen as a potential drug target due to its role in tryptophan biosynthesis. Residue N189 interacts with active site residues E168 and S220. It is inferred from previous studies done with …

Fulfilling Koch’S Postulates And Evaluation Of Different Administration Routes In Poults Challenged With Streptococcus Gallolyticus, Latasha Gray

Graduate Theses and Dissertations

Streptococcus gallolyticus (SG) is a Gram-positive found as commensal gut flora in animals and humans. SG has been associated with acute mortality in poults 2 to 3 weeks of age, with lesions mainly consisting of splenomegaly, hepatomegaly, and pericarditis. The objective of this thesis was to reproduce disease in poults caused by SG recovered from clinical field isolates and evaluate different routes of administration. Three field isolates from geographically disparate areas in Arkansas and Missouri were used for the experiments contained in this thesis. Antibiotic sensitives of the three field isolates revealed sensitivity to penicillin as well as a wide …

Evaluation Of The Effect Of Enterococcus Cecorum Exposure During Late Embryogenesis On Systemic Disease And Early Performance In Broiler Chickens, Marcela Arango

Graduate Theses and Dissertations

The objective of this thesis was to investigate the effects of Enterococcus cecorum (EC) administration into the amnion at day 18 of embryogenesis on performance and septicemia development in broiler chickens. Chapter I consists of a brief overview of the thesis. Chapter II provides a literature review on EC-related disease in broiler chickens and methods to isolate, detect, and differentiate between commensal and pathogenic strains of EC. Chapter III consists of a study conducted to determine if different EC strains isolated from field cases that exhibited septicemia and high mortality impacted hatchability, livability, organ colonization, and early performance in broiler …

An Ecological Perspective Of American Rodent-Borne Orthohantavirus Surveillance, Nathaniel Mull

Graduate Theses and Dissertations

Orthohantaviruses are a global group of viruses found primarily in rodents, though several viruses have also been found in shrews and moles. Many rodent-borne orthohantaviruses are capable of causing one of several diseases in humans, and the mortality associated with these diseases ranges from < 0.1% - 50% depending on the specific etiological virus. In North and South America, orthohantavirus research was ignited by an outbreak of severe disease in the Four Corners region of the United States in 1993. However, despite the discovery of over 20 orthohantaviruses in the Americas, our understanding of orthohantavirus ecology and virus-host dynamics in this region is still limited, and orthohantavirus surveillance is generally restricted in scope to select regions and small portions of host distributional ranges. In Chapter I, I present a literature review on the current understanding of American rodent-borne orthohantavirus ecology. This review focused on under-studied orthohantaviruses, addressing gaps in knowledge by extrapolating information from well-studied orthohantaviruses, general rodent ecology, and occassionally from Eurasian orthohantavirus-host ecology. There were several key conclusions generated from this review that warrant further research: 1) the large number of putative orthohantaviruses and gaps in orthohantavirus evolution necessitate further surveillance and characterization, 2) orthohantavirus traits differ and are more generalizable based on host taxonomy rather than geography, and 3) orthohantavirus host species are disproportionately found in grasslands and disturbed habitats. In Chapter II, I present a prioritized list of rodent species to target for orthohantavirus surveillance based on predictive modeling using machine learning. Probable orthohantavirus hosts were predicted based on traits of known orthohantavirus hosts using two different types of evidence: RT-PCR and virus isolation. Predicted host distributions were also mapped to identify geographic hotspots to spatially guide future surveillance efforts. In Chapter III, I present a framework for understanding and predicting orthohantavirus traits based on reservoir host phylogeny, as opposed to the traditional geographic dichotomy used to group orthohantaviruses. This framework establishes three distinct orthohantavirus groups: murid-borne orthohantaviruses, arvicoline-borne orthohantaviruses, and non-arvicoline cricetid-borne orthohantaviruses, which differ in several key traits, including the human disease they cause, transmission routes, and virus-host fidelity. In Chapter IV, I compare rodent communities and orthohantavirus prevalence among grassland management regimes. Sites that were periodically burned had high rodent diversity and a high proportion of grassland species. However, rodent seroprevalence for orthohantavirus was also highest in burned sites, representing a trade-off in habitat management outcomes. The high seroprevalence in burned sites is likely due to the robust populations supported by the high quality habitat resulting from prescribed burning. In Chapters V and VI, I describe Ozark virus and Sager Creek virus, two novel orthohantaviruses discovered from specimens collected during Chapter IV. Both chapters report full genome sequences of the respective viruses and compare both nucleotide and protein phylogenies with related orthohantaviruses. Additionally in Chapter VI, I support the genetic analyses with molecular and ecological characterizations, including seasonal fluctuations in host abundance, correlates of prevalence, evidence of virus shedding, and information on host cell susceptibility to Sager Creek virus.

Deficiency Of Adipose Aryl Hydrocarbon Receptor Protects Against Diet-Induced Metabolic Dysfunction Through Sexually Dimorphic Mechanisms, Nazmul Haque

Dissertations

Calorie imbalance due to high energy intake vs. expenditure is considered a major cause of obesity. Molecular mechanisms underlying diet-induced obesity remain unclear due to the complexity of disease progression. The impact of environmental factors contributing to obesity also remains poorly understood. Activation of the xenobiotic sensor, aryl hydrocarbon receptor (AhR), by obesogens may contribute to diet-induced obesity. AhR has the potential to influence lipid metabolism, insulin resistance, and the development of diabetes. Activation of AhR increases the risk of metabolic dysfunction by impairing adipose tissue function. Thus, the hypothesis was that conditional AhR depletion specifically from mature adipose tissue …

Bronze Monuments: The Terror Of Death And Its Role In The Great Gatsby, Samuel Talley

Masters Theses and Doctoral Dissertations

This thesis is about the way humans cope with death through the lens of F. Scott Fitzgerald’s The Great Gatsby in the wake of war. The thesis contains three chapters all of which work in succession to build a picture of various characters’ death denial. Chapter 2 considers how Nick’s narrative is an attempt to deny death through the ritual of mourning. Chapter 3 analyzes wealth in the novel and its role in striving for immortality. Gatsby transcends the limits of an ordinary life with his interest in opulence, while Nick’s wealth provides a level of privilege that allows for …

Dean's Research Newsletter, May 2023, Jerry L. Nadler

SOM Dean's Research Newsletter

No abstract provided.

Why The Vonoprazan Helicobacter Pylori Therapies In The Us-European Trial Produced Unacceptable Cure Rates, David Y Graham

Faculty, Staff and Students Publications

INTRODUCTION: Helicobacter pylori infects a large percentage of the world's population and is etiologically related to gastric cancer. The U.S. Food and Drug Administration recently approved two 14-day vonoprazan-containing regimens (vonoprazan-amoxicillin with or without clarithromycin) for H. pylori infections in the United States/Europe.

METHODS: We critically reviewed the trial methods to discover why the results were unacceptable low [i.e., no regimen achieved clinically acceptable (≥ 90%) or even conditionally acceptable cure rates (≥ 85%)]. Cure rates with antibiotic susceptible strains were 84.7 for vonoprazan triple therapy, 78.5 for vonoprazan-amoxicillin, and 78.7 for lansoprazole triple therapy, respectively. As was previously shown …

An Analysis Of Trends Of Generic Drugs And Biologic Prices In The U.S., Mohammed Jamjoom

Pharmaceutical Sciences (PhD) Dissertations

Introduction: Drug prices are a significant problem for the US healthcare system. Generic and biosimilar market competition reduces drug and biologic prices, results in substantial savings, and improves patient access and outcomes. As the costs of healthcare and prescription drugs continue to rise, the discussion about drug prices has taken a prominent place at the forefront of national discourse. This study assessed impacting trends in prices of generic, biosimilar, and reference products in the US. We also evaluated the effect of the Affordable Care Act (ACA) of 2010 on biologic prices.

Methods: We extracted a list of the new generic …

The Leaky Pipeline In Academia., Mary Anne Jackson

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Gender, Personality, And Cognitive Resilience Against Early-Life Disadvantage, Joseph L. Saenz, Sadaf Arefi Milani, Silvia Mejia-Arango

School of Medicine Publications

Objectives: Early-life disadvantage (ELD) relates to lower late-life cognition. However, personality factors, including having an internal locus of control (LOC) or a conscientious personality, relate to resilience and effective stress coping. We explore whether personality factors convey resilience against the negative effects of ELD on cognition, by gender, in Mexico.

Methods: Using the 2015 Mexican Health and Aging Study, we estimated expected cognition using multiple ELD markers to identify a subsample in the lowest quartile of expected cognition given ELD (n = 2,086). In this subsample, we estimated cross-sectional associations between personality and having above-median observed cognitive ability (n = …

Optimal R&D Investment In The Management Of Invasive Species, William Haden Chomphosy, Dale T. Manning, Stephanie A. Shwiff, Stephan Weiler

United States Department of Agriculture Wildlife Services: Staff Publications

Invasive alien species (IAS) threaten world biodiversity, ecosystem services, and economic welfare. While existing literature has characterized the optimal control of an established IAS, it has not considered how research and development (R&D) into new removal methods or technologies can affect management decisions and costs over time. R&D can lower the costs of control in a management plan and creates an intertemporal trade-off between quick but costly control and gradual but cheaper removal over time. In this paper, we develop and solve a continuous time dynamic optimization model to study how investment in R&D influences the optimal control of an …

Reducing Readmission Rates Among Patients Who Have A Dual Diagnosis Of Both Mental And Physical Illnesses, Hannah M. Shahan

Electronic Theses and Dissertations

Readmission rates are a primary indicator used by acute care hospitals to determine the effectiveness of healthcare treatments and interventions. High readmission rates indicate the existence of a gap in the continuum of care. Acute care hospitals focus on the treatment of the immediately urgent physical health condition. Once the immediate presenting illness is treated or stabilized, the patient is discharged. This focus largely leaves mental illness undiagnosed and untreated. However, chronic, untreated mental illnesses are often comorbid with physical illnesses. In studies comparing patients with comorbid physical and mental illness to patients with only a physical illness, comorbidity was …

Effect Of P2y12 Inhibitors On Organ Support-Free Survival In Critically Ill Patients Hospitalized For Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Matthew D Neal, Lucy Z Kornblith, Michelle N Gong, Harmony R Reynolds, Mary Cushman, Andrew D Althouse, Patrick R Lawler, Bryan J Mcverry, Keri S Kim, Lisa Baumann Kreuziger, Scott D Solomon, Mikhail N Kosiborod, Scott M Berry, Grant V Bochicchio, Marco Contoli, Michael E Farkouh, Joshua D Froess, Sheetal Gandotra, Yonatan Greenstein, Erinn M Hade, Nicholas Hanna, Kristin Hudock, Robert C Hyzy, Fátima Ibáñez Estéllez, Nicole Iovine, Ashish K Khanna, Pooja Khatri, Bridget-Anne Kirwan, Matthew E Kutcher, Eric Leifer, George Lim, Renato D Lopes, Jose L Lopez-Sendon, James F Luther, Lilia Nigro Maia, John G Quigley, Lana Wahid, Jennifer G Wilson, Ryan Zarychanski, Andrei Kindzelski, Mark W Geraci, Judith S Hochman, Activ-4a Investigators

Faculty, Staff and Students Publications

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19.

OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.

INTERVENTION: Participants were randomly assigned to receive a P2Y12 …

Immune Profiling Of Adeno-Associated Virus Response Identifies B Cell-Specific Targets That Enable Vector Re-Administration In Mice, Maria Chen, Boram Kim, Maria I Jarvis, Samantha Fleury, Shuyun Deng, Shirin Nouraein, Susan Butler, Sangsin Lee, Courtney Chambers, H Courtney Hodges, Jerzy O Szablowski, Junghae Suh, Omid Veiseh

Faculty, Staff and Students Publications

Adeno-associated virus (AAV) vector-based gene therapies can be applied to a wide range of diseases. AAV expression can last for months to years, but vector re-administration may be necessary to achieve life-long treatment. Unfortunately, immune responses against these vectors are potentiated after the first administration, preventing the clinical use of repeated administration of AAVs. Reducing the immune response against AAVs while minimizing broad immunosuppression would improve gene delivery efficiency and long-term safety. In this study, we quantified the contributions of multiple immune system components of the anti-AAV response in mice. We identified B-cell-mediated immunity as a critical component preventing vector …

Adad2 Functions In Spermiogenesis And Pirna Biogenesis In Mice, Yonggang Lu, Ippei Nagamori, Hisato Kobayashi, Kanako Kojima-Kita, Kenjiro Shirane, Hsin-Yi Chang, Toru Nishimura, Takayuki Koyano, Zhifeng Yu, Julio M Castañeda, Makoto Matsuyama, Satomi Kuramochi-Miyagawa, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

BACKGROUND: Adenosine deaminase domain containing 2 (ADAD2) is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive.

OBJECTIVES: This study aimed to investigate the cause of male sterility in Adad2 mutant mice and to understand the molecular functions of ADAD2.

MATERIALS AND METHODS: Adad2 homozygous mutant mouse lines, Adad2

RESULTS: Adad2–/– and Adad2Δ/Δ mice exhibit male-specific sterility due to abnormal spermiogenesis. ADAD2 interacts with multiple RNA-binding proteins involved in …

Endogenous Interleukin-10 Contributes To Wound Healing And Regulates Tissue Repair, Walker D Short, Meredith Rae, Thomas Lu, Benjamin Padon, Tanuj J Prajapati, Fayiz Faruk, Oluyinka O Olutoye, Ling Yu, Paul Bollyky, Sundeep G Keswani, Swathi Balaji

Faculty, Staff and Students Publications

INTRODUCTION: Interleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well-established. We sought to determine the function of endogenous IL-10 in murine full thickness excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure.

METHODS: Full-thickness excisional wounds were made in wildtype (WT) and IL-10

RESULTS: We observed no difference in wound healing rate between WT and IL-10

CONCLUSIONS: These data suggest that endogenous IL-10 expression does not alter closure of full …

Bladder Mucosal Cystitis Cystica Lesions Are Tertiary Lymphoid Tissues That Correlate With Recurrent Urinary Tract Infection Frequency In Postmenopausal Women, Marianne M Ligon, Brooke Liang, Stacy M Lenger, Priyanka Parameswaran, Siobhan Sutcliffe, Jerry L Lowder, Indira U Mysorekar

Faculty, Staff and Students Publications

PURPOSE: We identify correlates and clinical outcomes of cystitis cystica, a poorly understood chronic inflammatory bladder change, in women with recurrent urinary tract infections.

MATERIALS AND METHODS: A retrospective, observational cohort of women with recurrent urinary tract infections who underwent cystoscopy (n=138) from 2015 to 2018 were identified using electronic medical records. Cystitis cystica status was abstracted from cystoscopy reports and correlations were identified by logistic regression. Urinary tract infection-free survival time associated with cystitis cystica was evaluated by Cox proportional hazards regression. Exact logistic regression was used to identify factors associated with changes to cystitis cystica lesions on repeat …

The Impact Of Initial Specimen Diversion Systems On Blood Culture Contamination, Mayar Al Mohajer, Todd Lasco

Faculty, Staff and Students Publications

Blood culture contamination is associated with increased antimicrobial use, length of stay, and hospital cost. To address this problem, blood culture diversion has been developed as an additional measure to reduce contamination to targeted goals. Three different versions were proposed, including an open technique and 2 commercially available devices. This study aims to review the existing literature and analyze evidence for these 3 techniques.

Extracorporeal Membrane Oxygenation Characteristics And Outcomes In Children And Adolescents With Covid-19 Or Multisystem Inflammatory Syndrome Admitted To Us Icus, Melania M Bembea, Laura L Loftis, Ravi R Thiagarajan, Cameron C Young, Timothy P Mccadden, Margaret M Newhams, Suden Kucukak, Elizabeth H Mack, Julie C Fitzgerald, Courtney M Rowan, Aline B Maddux, Amanda R Kolmar, Katherine Irby, Sabrina Heidemann, Stephanie P Schwartz, Michele Kong, Hillary Crandall, Kevin M Havlin, Aalok R Singh, Jennifer E Schuster, Mark W Hall, Kari A Wellnitz, Mia Maamari, Mary G Gaspers, Ryan A Nofziger, Peter Paul C Lim, Ryan W Carroll, Alvaro Coronado Munoz, Tamara T Bradford, Melissa L Cullimore, Natasha B Halasa, Gwenn E Mclaughlin, Pia S Pannaraj, Natalie Z Cvijanovich, Matt S Zinter, Bria M Coates, Steven M Horwitz, Charlotte V Hobbs, Heda Dapul, Ana Lia Graciano, Andrew D Butler, Manish M Patel, Laura D Zambrano, Angela P Campbell, Adrienne G Randolph

Faculty, Staff and Students Publications

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed.

DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry.

SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021.

PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria …

Leveraging The Electronic Health Record To Implement Emergency Department Delirium Screening, Anita N Chary, Elise Brickhouse, Beatrice Torres, Ilianna Santangelo, Christopher R Carpenter, Shan W Liu, Kyler M Godwin, Aanand D Naik, Hardeep Singh, Maura Kennedy

Faculty, Staff and Students Publications

OBJECTIVE: The aim of this study is to understand how emergency departments (EDs) use health information technology (HIT), and specifically the electronic health record (EHR), to support implementation of delirium screening.

METHODS: We conducted semi-structured interviews with 23 ED clinician-administrators, representing 20 EDs, about how they used HIT resources to implement delirium screening. Interviews focused on challenges participants experienced when implementing ED delirium screening and EHR-based strategies they used to overcome them. We coded interview transcripts using dimensions from the Singh and Sittig sociotechnical model, which addresses use of HIT in complex adaptive health care systems. Subsequently, we analyzed data …

Madm For Assessment The Nurses Knowledge And Their Attitudes During Covid-19 Spread In Mosul City In The Perspective Of Neutrosophic Environment, Ihsan H. Zainel, Huda E. Khalid

Neutrosophic Sets and Systems

No abstract provided.

Gwas And Meta-Analysis Identifies 49 Genetic Variants Underlying Critical Covid-19, Erola Pairo-Castineira, Konrad Rawlik, Andrew D Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A Mcconkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny Mcauley, Hugh Montgomery, Peter J M Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, José A Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Genomicc Investigators, Scourge Consortium, Isaricc Investigators, 23andme Covid-19 Team, Jian Yang, Chris P Ponting, James F Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D Luchessi, Esteban J Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J Kenneth Baillie

Faculty, Staff and Student Publications

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a …

Investigation Into The Roles Of Esxa N-Α-Acetylation In Pathogenesis Of Mycobacterium Tuberculosis And Potential Host-Binding Proteins, Javier Aguilera

Open Access Theses & Dissertations

EsxA (6-kDa early secreted antigenic target, ESAT-6) is a critical virulence factor of Mycobacterium tuberculosis (Mtb). EsxA is secreted in a heterodimer with EsxB (10-kDa culture filtrate protein, CFP-10) through the Type VII secretion system of Mtb, called ESX-1. The dissociation of EsxA and EsxB heterodimer (EsxA:B), upon acidification, is required for EsxA to penetrate into the phagosomal membranes, which has been implicated in Mtb translocation from the phagosome to the cytosol. However, the mechanism of EsxA:B dissociation is not clear. In this study, we investigated the role of N-α-acetylation of EsxA in the heterodimer dissociation, mycobacterial cytosolic translocation, and …

A Novel Neuroinvasive Infection Modality For Francisella Tularensis Elicits Neuroinflammation Resulting In Cellular Damage, Mireya Griselle Ramos-Muniz

Open Access Theses & Dissertations

Francisella tularensis (Ft.) is a gram-negative coccobacillus bacterium that causes the zoonotic disease tularemia in humans. Ft. causes the most severe, often fatal, form of the disease through inhalation. However, Ft. is most commonly transmitted through direct contact with infected animal carcasses such as rodents and rabbits, consumption of contaminated food or water, or through arthropod bites, particularly ticks. Due to its extremely low infectious dose, high mortality rate, and potential use as a biological warfare agent, Ft. is classified by the CDC as a "Tier 1 select agent". Ft. infection triggers an overactive inflammatory response, termed a "cytokine storm", …

Social Reproduction And Covid-19, Caroline I. Donovan

Dartmouth College Master’s Theses

As Covid-19 rips across the world we are collectively asked to examine the structures of society to see what is working and what we can change. What can we learn from the roughly 6.9 million deaths (and counting) worldwide? How can we prevent something like this from happening again? This paper follows the course of Covid-19 from its birth in Wuhan, China, to the present day of mid-April 2023. By looking at the ways in which we have reacted to the pandemic, we are able to look forward and imagine new ways of tackling future pandemics and other pressing problems …