Diseases Commons^™

The Rsv F P27 Peptide: Current Knowledge, Important Questions, Wanderson Rezende, Hadley E Neal, Rebecca E Dutch, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) remains a leading cause of hospitalizations and death for young children and adults over 65. The worldwide impact of RSV has prioritized the search for an RSV vaccine, with most targeting the critical fusion (F) protein. However, questions remain about the mechanism of RSV entry and RSV F triggering and fusion promotion. This review highlights these questions, specifically those surrounding a cleaved 27 amino acids long peptide within F, p27.

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi-modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite-related gene signature and altered metabolic pathways associated with LUAD and LUSC.

METHODS: We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co-expression was used to identify modules of metabolites that were altered between normal and tumor.

RESULTS: We identified unique metabolite-related gene signatures specific for …

Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar

Faculty, Staff and Students Publications

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial …

Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman

Faculty, Staff and Students Publications

Effective de-implementation models often include replacement of an ineffective practice with an alternative. We co-developed patient education materials as a replacement strategy for inappropriate post-procedural antibiotics in cardiac device procedures. Lessons learned and developed materials may be used to promote infection prevention in other periprocedural settings.

Combining Charlson Comorbidity And Vacs Indices Improves Prognostic Accuracy For All-Cause Mortality For Patients With And Without Hiv In The Veterans Health Administration, Kathleen A Mcginnis, Amy C Justice, Vincent C Marconi, Maria C Rodriguez-Barradas, Ronald G Hauser, Krisann K Oursler, Sheldon T Brown, Kendall J Bryant, Janet P Tate, Veterans Aging Cohort Study Affiliations

Faculty, Staff and Students Publications

INTRODUCTION: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index.

METHODS: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components …

Clinical Approach To Evaluation Of Underlying Cardiac Device Infection In Patients Hospitalized With Bacteremia, Dierdre B Axell-House, Sarwat Khalil, M Rizwan Sohail

Faculty, Staff and Students Publications

More than 400,000 cardiac implantable electronic devices (CIEDs), including permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, are implanted every year in the United States (US). Infection is a serious complication of CIED therapy and is associated with high morbidity and mortality. While CIED pocket infection can be diagnosed based on clinical exam findings, positive blood culture may be the only manifestation of CIED lead infection. Thus, management of bacteremia in patients living with CIEDs requires special consideration. This review summarizes contemporary data in the context of the recently updated 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for …

Real-World Experience With Cefiderocol Therapy For Pseudomonas Aeruginosa And Other Multidrug Resistant Gram-Negative Infections Within The Veterans Health Administration, 2019–2022, Andrew Chou, David Ramsey, Eva Amenta, Barbara W Trautner

Faculty, Staff and Students Publications

OBJECTIVE: Single-center and regional studies have reported outcomes after treatment with cefiderocol, a novel siderophore cephalosporin. We report on real-world use, clinical outcomes, and microbiological outcomes with cefiderocol therapy within the Veterans' Health Administration (VHA).

DESIGN: Prospective, observational descriptive study.

SETTING: Veterans' Health Administration, 132 sites across the United States, during 2019-2022.

PATIENTS: This study included patients admitted to any VHA medical center who received cefiderocol for ≥2 days.

METHODS: Data were obtained from the VHA Corporate Data Warehouse and through manual chart review. We extracted clinical and microbiologic characteristics and outcomes.

RESULTS: In total, 8,763,652 patients received 1,142,940,842 prescriptions …

Bacteriuria In Older Adults Triggers Confusion In Healthcare Providers: A Mindful Pause To Treat The Worry, Eva M Amenta, Robin L P Jump, Barbara W Trautner

Faculty, Staff and Students Publications

The evidence base for refraining from screening for or treating asymptomatic bacteriuria (ASB) in older adults is strong, but both practices remain prevalent. Clinical confusion over how to respond to a change from baseline, when to order a urinalysis and urine culture, and what to do with a positive urine culture fuels unnecessary antibiotic use for ASB. If the provider can take a mindful pause to apply evidenced-based assessment tools, the resulting increased clarity in how to manage the situation can reduce overtreatment of ASB.

Range And Consistency Of Cardiovascular Outcomes Reported By Clinical Trials In Kidney Transplant Recipients: A Systematic Review, Gregory J Wilson, Kim Van, Emma O'Lone, Allison Tong, Jonathan C Craig, Benedicte Sautenet, Klemens Budde, Derek Forfang, John Gill, William G Herrington, Tazeen H Jafar, David W Johnson, Vera Krane, Adeera Levin, Jolanta Malyszko, Patrick Rossignol, Deirdre Sawinski, Nicole Scholes-Robertons, Giovanni Strippoli, Angela Wang, Wolfgang C Winkelmayer, Carmel M Hawley, Andrea K Viecelli

Faculty, Staff and Students Publications

BACKGROIUND: Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients.

METHODS: A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of …

Melatonin Attenuates Mitochondrial Damage In Aristolochic Acid-Induced Acute Kidney Injury, Jian Sun, Jinjin Pan, Qinlong Liu, Jizhong Cheng, Qing Tang, Yuke Ji, Ke Cheng, Rui Wang, Liang Liu, Dingyou Wang, Na Wu, Xu Zheng, Junxia Li, Xueyan Zhang, Zhilong Zhu, Yanchun Ding, Feng Zheng, Jia Li, Ying Zhang, Yuhui Yuan

Faculty, Staff and Students Publications

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro …

Documented Adverse Drug Reactions And Discontinuation Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers In Chronic Kidney Disease, L Parker Gregg, Peter A Richardson, Michael A Herrera, Julia M Akeroyd, Shehrezade A Jafry, Glenn T Gobbel, Sheena Wydermyer, Jennifer Arney, Adriana Hung, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation.

METHODS: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …

Distinct Temporal Trajectories And Risk Factors For Post-Acute Sequelae Of Sars-Cov-2 Infection, Chen Chen, Sairam Parthasarathy, Jacqueline M Leung, Michelle J Wu, Katherine A Drake, Vanessa K Ridaura, Howard C Zisser, William A Conrad, Victor F Tapson, James N Moy, Christopher R Defilippi, Ivan O Rosas, Bellur S Prabhakar, Mujeeb Basit, Mirella Salvatore, Jerry A Krishnan, Charles C Kim

Faculty, Staff and Students Publications

BACKGROUND: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.

METHODS: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection.

RESULTS: We identified three phenotypic clusters associated with PASC that could be characterized as …

Lymphangioleiomyomatosis: Circulating Levels Of Fgf23 And Pulmonary Diffusion, Anthony J Esposito, Jewel Imani, Shikshya Shrestha, Shefali Bagwe, Anthony M Lamattina, Marina Vivero, Hilary J Goldberg, Ivan O Rosas, Elizabeth P Henske, Souheil Y El-Chemaly

Faculty, Staff and Students Publications

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.

METHODS: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM …

A Rare Case Of Isolated Thoracic Al-Amyloidoma Causing Complete Atelectasis Of The Right Lung, Smruti Rath, Nicholas Joseph Dcunha, Neel Bhan, Bettye Cox, Muhammad Adrish

Faculty, Staff and Students Publications

Tumoral amyloidosis, or amyloidoma, is a benign, but rare form of amyloidosis that has been reported with a favorable prognosis following surgical resection in some case reports. We present a case of acute on chronic respiratory failure secondary to extensive growth of a thoracic amyloidoma causing atelectasis of the right lung. Our case patient had greater morbidity due to late presentation and extensive disease at diagnosis, precluding any surgical intervention. Radiation therapy and medical management were unsuccessful in reducing disease burden. Early diagnosis and detection are pivotal to improving survival in patients with isolated thoracic amyloidoma.

Is It Time To Switch To Bivalirudin For Ecmo Anticoagulation?, Amir Navaei, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

For decades, unfractionated heparin (hereafter, heparin) has been the primary anticoagulant used for extracorporeal membrane oxygenation (ECMO) support. More recently, however, bivalirudin, a direct thrombin inhibitor, has emerged as an alternative. This systematic review based on PRISMA guidelines, aims to summarize 16 comparative studies and 8 meta-analysis and review articles published from January, 2011 till May, 2023 which directly compares ECMO courses using heparin versus bivalirudin as the anticoagulant. While this comparison is complicated by the lack of a standardized definition of major bleeding or thrombosis, our overall findings suggest there is no statistical difference between heparin and bivalirudin in …

Weight Strategy In Older Adults With Obesity: Calorie Restriction Or Not?, Georgia Colleluori, Dennis T Villareal

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults.

RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. …

Genetic Sequencing Of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections In Fully Vaccinated Healthcare Workers, Sara Haddad, John Zurlo, Zi-Xuan Wang, Bonnie Richards, Nitika Badjatia, Dagan Coppock

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Introduction

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several efforts have been made to prevent infection, culminating in the development of highly effective vaccines. However, as genetic variants of the virus have emerged, concerns have arisen regarding potential limitations of available vaccines.

Methods

In this article, we evaluated SARS-CoV-2 breakthrough infections among 520 healthcare workers in a 950-bed hospital from March 1, 2021, to October 31, 2021, and stratified them according to the type of vaccine received. We tested for associations between Alpha and Delta strains of SARS-CoV-2 and clinical characteristics.

Results

During the study period, …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

Determinants Of Retention In Care Of Newborns Diagnosed With Sickle Cell Disease In Liberia: Results From A Mixed-Methods Study Of Caregivers, Kanagasabai Udhayashankar, Patience D Franklin, Cecelia J Nuta, Adolphus K Cherue, Heather Haq, Debbe Thompson, Venée N Tubman

Faculty, Staff and Students Publications

High-income nations have established that early diagnosis and preventive treatment reduces early deaths in sickle cell disease (SCD). However, in low-/middle-income countries where SCD is common, attrition from clinical care is common. Reasons for poor retention in care are multi-factorial and poorly understood. The objective of this study was to identify factors that influence caregiver decision-making around chronic health care needs of a child with SCD. We conducted an exploratory sequential mixed methods study of caregivers of children diagnosed with SCD during a newborn screening program in Liberia. Caregivers completed questionnaires and semi-structured interviews designed to identify drivers of health …

Cholestasis Impairs Gut Microbiota Development And Bile Salt Hydrolase Activity In Preterm Neonates, Lauren E Lynch, Amy B Hair, Krishnakant G Soni, Heeju Yang, Laura A Gollins, Monica Narvaez-Rivas, Kenneth D R Setchell, Geoffrey A Preidis

Faculty, Staff and Students Publications

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops …

Stressors And Hormone Levels: Predictors Of Covid-19 Health Outcomes In Latine Adults, Wendy Rodriguez

CMC Senior Theses

The Coronavirus 2019 Disease (COVID-19) has been shown by multiple studies to have disproportionate impacts on some individuals, especially minority populations. These may be attributed to differences in biological (sex), gender, social or cultural factors. In this study, we aim to identify and investigate the gender and social predictors that may be involved in the pathogenesis of the virus and its health outcomes. To achieve this, a literature review expands on relevant topics that better contextualize COVID-19’s complex nature. The potential role of hormones, estrogen, and testosterone is considered across different sexes and genders as protective agents against COVID-19. This …

Analysis Of Multi-Drug Resistant Mycobacterium Tuberculosis Using Split Deoxyribozymes, Abryana Fergus

Electronic Theses and Dissertations, 2020-2023

Globally, tuberculosis, a disease caused by the species of Mycobacterium tuberculosis (Mtb) complex, stands as a leading cause of death from a single infectious agent. Even though antituberculous drugs are available, treatment is challenging due to antibiotic resistance associated with point mutations in the bacterial genome. Resistance to the first-line antibiotics – rifampin and isoniazid – results in multidrug-resistant tuberculosis (MDR) requiring a more complicated treatment regimen. Timely and accurate identification of drug-resistant TB cases can help prescribe the most effective treatment and prevent the spread of infection. This research aims to develop an assay to discern multi-drug resistant forms …

Evaluating The Impact Of Using A Wound-Specific Oral Nutritional Supplement To Support Wound Healing In A Rehabilitation Setting, Rya K Clark, Argyrios Stampas, Kirk W Kerr, Jeffrey L Nelson, Suela Sulo, Luis Leon-Novelo, Esther Ngan, Dehuti Pandya

Faculty, Staff and Student Publications

Chronic wounds adversely affect patient quality of life, increase the risk of mortality, and impose high costs on healthcare systems. Since protein-energy malnutrition or specific nutrient deficiencies can delay wound healing, nutritionally focused care is a key strategy to help prevent or treat the occurrence of non-healing wounds. The objective of our study of inpatients in a rehabilitation hospital was to quantify the effect of daily wound-specific oral nutritional supplementation (WS-ONS) on healing chronic wounds. Using electronic medical records, we conducted a retrospective analysis of patients with chronic wounds. We identified records for (a) a treatment group who received standard …

Advance Care Planning In Cancer Patient - Caregiver Dyads, Natasha Michael

Theses

For many, a cancer diagnosis signals death's inevitability and elicits much existential concern. In the quest for life prolongation, many are offered or seek life-sustaining treatments, fail to appreciate a declining trajectory and lack the opportunity to seek information or plan meaningfully for their future.

Advance care planning (ACP) provides an avenue for patients and their caregivers to plan for future care. ACP is defined ‘as a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals and preferences regarding future medical care’ and is a key quality indicator in …

A Machine Learning Approach For Early Diagnosis Of Transthyretin Amyloid Cardiomyopathy Among Heart Failure Patients, Tanjim Ahmed

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, progressive, and fatal disease. Prevalence of ATTR-CM ranges from 4 to 17 per 100000 cases where the mean survival time is less than 4 years. It has a history of being underdiagnosed and misdiagnosed. The diagnosis delay has a weighted mean of 6.1 years for wild-type ATTR-CM. Low awareness, the necessity of invasive procedures, and lack of treatment are the key reasons for delayed diagnosis. But, with the introduction of non-invasive tests like nuclear scintigraphy with ^99mTC-PYP and the disease modifying drug Tafamidis, the diagnosis delay signifies a missed opportunity to increase …

Health-Related Quality Of Life And Disease Severity Among Patients With Idiopathic Pulmonary Fibrosis, Rowida Mohamed

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Predicting the survival of patients with Idiopathic pulmonary fibrosis (IPF) remains challenging due to the remarkable heterogeneity of the disease prognosis. Therefore, developing reliable prognostic tools is of utmost importance in IPF management. Nomograms currently represent the most accurate and discriminatory tools for predicting outcomes, with superior performance compared to the commonly used integer score approach. Therefore, developing a valid local nomogram to predict mortality among patients with IPF is warranted. Additionally, IPF is characterized by a high symptom burden significantly impacting Health-related quality of life (HRQoL). Accurately measuring HRQoL in IPF is crucial as it guides treatment decisions …

Glial Cell-Specific Contribution Of Pkr-Like Er Kinase (Perk) In Neuroinflammation And Behavior, Anirudhya Lahiri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological disorders such as multiple sclerosis (MS) are a major public health concern in the US, with no available therapeutic cure. Chronic neuroinflammation and aberrant proteostasis in the central nervous system (CNS) are the major hallmarks of neurological diseases. Endoplasmic Reticulum (ER) is a major cellular organelle involved in protein synthesis, folding and maturation of various secretory and transmembrane proteins. Pathophysiological stressors such as trauma and infection result in misfolded protein accumulation in the endoplasmic reticulum (ER) lumen, which results in ER stress. To regain proteostasis (protein homeostasis), cells activate the unfolded protein response (UPR). UPR is an evolutionarily conserved …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …

Evaluation Of A Novel Mrna-Pertussis Vaccine Against Emerging Clinical Isolates Of Bordetella Pertussis, Graham Jeffrey Bitzer

Graduate Theses, Dissertations, and Problem Reports (ETD)

Bordetella pertussis is a Gram-negative obligate aerobe that causes a respiratory disease known as pertussis or whooping cough. Pertussis is most severe in younger children, especially infants but the bacteria has been known to colonize adult populations. Before the introduction of the whole-cell pertussis (wP; wP-DTP) vaccine reported numbers of pertussis cases within the US routinely topped 100,000 cases per year. However, with the widespread usage of the wP vaccine case numbers began dropping and reached a low of less than 5,000 cases per year in the late 1970’s and early 80’s. It appeared that B. pertussis was heading towards …