Immune System Diseases Commons^™

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

Quantifying The Heterogeneity Of The Immunoglobulin G N-Glycome In An Ageing Australian Population: The Busselton Healthy Ageing Study, Alyce Russell

Theses: Doctorates and Masters

The use of immunoglobulin G N-glycomics to study chronic non-communicable disorders and other complex phenotypes emerged following the Human Genome Project. The consortium discovered that most phenotypes were too complex to be explained by genetics alone. Thus, the biological importance of epigenetics was recognised; heritable modifications to gene expression rather than the genome itself. Nglycosylation is a form of epigenetic regulation known as a post-translational modification. It stabilises the immunoglobulin G structure and alters downstream responses elicited by the antibody and is extensively studied as a candidate biomarker in the post-genomic era.

The N-glycosylation of immunoglobulin G itself is complex, …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …

The Relationship Between Biofilm Production And Human Respiratory Cell Attachment And Invasion By Acinetobacter Baumannii, Rachel A. Pearson

Theses and Dissertations

Acinetobacter baumannii is an opportunistic gram-negative bacterial pathogen that causes many nosocomial infections in immunocompromised individuals. Common infections include catheter-associated urinary tract infections, ventilator-associated pneumonia, skin and soft tissue infections, and bloodstream infections that often lead to septicemia. Increasing multidrug resistance (MDR) in A. baumannii warrants new approaches to understanding its virulence mechanisms and pathogenicity. As a first step in infection, A. baumannii can attach to host cells, providing a surface for the bacteria to grow and perhaps facilitating biofilm formation and subsequent tissue invasion. In this study, we evaluated antibiotic resistance and characterized biofilm formation, attachment, invasion, and surface …

Eugenics In The 21st Century, Jessica Linn Chin

Dissertations, Theses, and Capstone Projects

Eugenics is the science of enhancing the human population through the management of breeding and hereditary traits. This thesis explores the history of eugenics and shows how eugenic practices continue in the 21^st century with advancements in technology and positive eugenic goals that can result in adverse effects on the human body and society. When Sir Francis Galton coined the term eugenics in 1883, he intended to improve British society with the use of positive eugenics. Galton used positive eugenics to encourage people with good mental and physical qualities to produce more children. He avoided negative eugenics, which involved …

Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …

Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew

Master's Theses

Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are …

An Application Of The Modifiable Areal Unit Problem: Optimizing Cluster Method Parameters To Produce Predictive Data For Hiv Outbreaks, Connor J. Chato, Art Fy Poon

Western Research Forum

Background

A popular approach to study HIV outbreaks is to cluster cases based on genetic similarity. However, there is no widely-used statistical criterion which optimizes the parameters for sequence-based clustering methods. The relationship between a cluster-defining similarity threshold and it’s associated set of clusters can be analogized to the aggregation level in the Modifiable Areal Unit Problem (MAUP).

Hypothesis

Based on the selection of aggregation level for study partitions in MAUP, we present a statistical framework to optimize the similarity threshold for pairwise distance algorithm TN93 (http://github.com/veg/tn93). We hypothesize that defining this threshold includes case connections such that …

Male Determining Gene Nix May Bring An End To Transmission Of Diseases Through Mosquitoes, Mohammed Mahdi

Thinking Matters Symposium Archive

Female mosquitoes take blood from humans to gain protein needed to produce eggs, and in the process they can transmit viruses, such as Zika, Dengue, and chikungunya, or parasites, such as malaria. Male mosquitoes do not transmit diseases. This literature review will examine what is known about how sex is determined in mosquitoes and how this can be used to manipulate the females that spread diseases to humans. Using CRISPR Cas9, the lab of Zhijian Tu removed the Nix gene from mosquito embryos; all of these were feminized. Ectopic overexpression of Nix gene product in mosquito embryos caused even genetically …

From The American People: An Autoethnographic Exploration Of South African Ngos' Perceptions Of Pepfar, Antonia Asher

Independent Study Project (ISP) Collection

The aim of this research was to understand what the ideal partnership would be between United States (US) governmental aid agencies and South African non-governmental organizations (NGOs), specifically concerning HIV/AIDS programs funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR), from the perspective of NGOs. PEPFAR is the largest relief fund for a single disease; thus, I additionally sought to deeply reflect upon myself as a US citizen in South Africa, a country that has received trillions of dollars from taxpayers such as myself.

To accomplish this, I interviewed NGO staff about the nature of current partnerships, outcomes …

Clonally Expanded Alpha-Chain T-Cell Receptor (Tcr) Transcripts Are Present In Aneurysmal Lesions Of Patients With Abdominal Aortic Aneurysm (Aaa), Song Lu, John V. White, Raquel I. Judy, Lisa L. Merritt, Wan Lu Lin, Xiaoying Zhang, Charalambos Solomides, Ifeyinwa Nwaneshiudu, John Gaughan, Dimitri S. Monos, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Abdominal aortic aneurysm (AAA) is a life-threatening immunological disease responsible for 1 to 2% of all deaths in 65 year old or older individuals. Although mononuclear cell infiltrates have been demonstrated in AAA lesions and autoimmunity may be responsible for the initiation and account for the propagation of the disease, the information available about the pathogenesis of AAA is limited. To examine whether AAA lesions from patients with AAA contain clonally expanded α-chain TCR transcripts, we amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR these α-chain TCR transcripts. The amplified transcripts were cloned and sequenced. Substantial proportions …

Stat5b And Stat5 Tetramers Are Essential For Ige-Mediated Mast Cell Function, Kasalina N. Kiwanuka

Theses and Dissertations

Signal Transducers and Activators of Transcription (STATs) are latent transcription factors that mediate several cellular responses. This protein family consists of seven members, STAT1 – 6 including two closely related molecules, STAT5a and STAT5b, that show 96% amino acid sequence homology and are critical for lymphoid, myeloid and erythroid cell development and function. Activated STAT proteins dimerize and translocate to the nucleus, where they bind to high-affinity DNA motifs to modulate gene expression. We recently identified STAT5b as the critical regulator of IgE-mediated cytokine production in mast cells. STAT5b knockout (KO) cells show decreased sensitivity to IgE-mediated passive systemic anaphylaxis …

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …

Targeting Pro-Inflammatory Function Of Microglia Using Small Molecules To Combat Neurodegeneration, Gabrielle C. Williams, Priya Prakash, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Microglia are the brain’s resident immune cells that are responsible for maintaining homeostasis in healthy conditions. During injury or infection, resting microglia get activated and produce pro-inflammatory cytokines such as IL-1b, IL-1a, IL-6, etc. along with reactive oxygen species like nitric oxide (NO) to combat neuroinflammatory diseases such as Alzheimer’s disease (AD). Inflammation is characterized by the activation of resident-immune cells in the brain called microglia that respond to the eat-me signals released by the toxic amyloid beta peptides as well as the dying neurons in the microenvironment. Recent studies have shown that activated microglia induce neuronal death by secreting …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Inhibition Of Tnf-Alpha Decreases Microglia Activation In Rats Neonatally Treated With Poly I:C, Heath W. Shelton, Russell W. Brown

Appalachian Student Research Forum

Introduction: Current medical treatment for individuals diagnosed with schizophrenia (SCHZ) primarily relies on the inhibition of the dopamine D₂ receptor that has been shown to be supersensitive in these patients. Treatment occurs through the use of antipsychotic medication which leads to a number of debilitating dose-dependent side effects, such as weight gain, agranulocytosis, and seizures. Patients diagnosed with SCHZ have also been shown to have increased inflammation in their central nervous system (CNS), particularly within specific brain regions such as the prefrontal cortex and hippocampus. This is in large part due to the interaction between a pro-inflammatory cytokine called …

Calnexin Is Necessary For T Cell Transmigration Into The Central Nervous System, Amber M. Paul, Joanna Jung, Paul Eggleton, Alison Robinson, Jessica Wang, Nick Gutowski

Publications

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune …

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

UNO Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and …

Frequency And Factors Associated With Adult Immunization In Patients Visiting Family Medicine Clinics At A Tertiary Care Hospital, Karachi, Samar Zaki, Asma Usman, Swaleha Tariq, Sameena Shah, Iqbal Azam Syed, Waris Qidwai, Kashmira Nanji

Department of Family Medicine

Objective: The goal of this study was to determine the frequency and factors associated with adult immunization in patients visiting family medicine clinics at a tertiary care hospital in Karachi.
Methods: A cross-sectional study was conducted from March 2014 to March 2015 in a tertiary care hospital in Karachi, Pakistan. Participants more than 18 years were invited to participate in the study. A pretested questionnaire was used to collect information. Data were entered and analyzed using IBM SPSS Statistics for Windows, version 19.0 (Armonk, NY: IBM Corp).
Results: A total of 340 patients were surveyed. The majority of patients …

Interleukin-6 And Exercise; Early Evidence Of A Novel Myokine, Brendan Hogg Mr.

Graduate Student Theses, Dissertations, & Professional Papers

Interleukin-6 (IL-6) was first identified as a pleiotropic cytokine, with a host of body-wide functions. Cytokine functions are characterized by chronically elevated levels within various inflammatory states. In this regard, IL-6 is largely associated with the acute phase response to many stimuli and performs specific actions when produced from certain cell types. Accrued evidence indicates IL-6 release from skeletal muscle often includes myokine functions. Novel myokine functions are adaptive in nature, and as compared to inflammatory/cytokine roles, exhibit a transient time course. Following exercise plasma IL-6 peaks and returns to resting levels within 1-2 hours. In contrast, IL-6 is observed …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Activation Des Éosinophiles Humains Par Des Nanoparticules, Denis Girard, Maxime Marion-Murphy

Rapports de recherche scientifique

L’économie du Canada, comme celle de bien d’autres pays industrialisés, bénéficie du développement des nanotechnologies dont le fort potentiel peut être exploité dans plusieurs secteurs industriels. Un nombre croissant d’entreprises québécoises de production de nanoparticules (NP) est d’ailleurs déjà implanté et tout porte à croire que d’autres emboîteront le pas dans les années à venir. Ce faisant, non seulement le nombre de travailleurs œuvrant dans la fabrication et la synthèse des NP augmentera sensiblement, mais également le nombre de ceux qui seront appelés à en manipuler et à en transformer dans les domaines des nanotechnologies en général. Une des conséquences …

Mathematical Medicine: Modeling Disease And Treatment, Lisette Depillis

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Gender Differences In Virologic Response After Antiretroviral Therapy In Treatment-Naïve Hiv-Infected Individuals: Results From The 550 Clinic Hiv Cohort Study., Andrea Reyes-Vega, Alejandra Loban, Kavitha Srinivasan, Stephen P. Furmanek, Conner English, Mary Bishop, Cathy Spencer, Daniel Truelove, Julio A. Ramirez, Anupama Raghuram, Paula Peyrani

Faculty and Staff Scholarship

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results

A total of 70 women and 90 men were included …

Immune Checkpoint Inhibition And The Prevalence Of Autoimmune Disorders Among Patients With Lung And Renal Cancer, Sherif M. El-Refai

Pharmaceutical Sciences Faculty Publications

PURPOSE: Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation. We sought to identify, among patients with lung and renal cancer, how many harbor a comorbid autoimmune condition and may be at risk of worsening their condition while on immune checkpoint inhibitors such as nivolumab and pembrolizumab.

METHODS: An administrative health care claims database, Truven MarketScan, was used to identify patients diagnosed with lung and renal cancer from 2010 to 2013. We assessed patients …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was believed to have …

A Novel Multi-Network Approach Reveals Tissue-Specific Cellular Modulators Of Fibrosis In Systemic Sclerosis, Jaclyn N. Taroni, Casey S. Greene, Viktor Martyanov, Tammara A. Wood

Dartmouth Scholarship

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology.We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …