Medicine and Health Sciences Commons^™

Molecular Mechanisms Of Antimicrobial Resistance In Multi-Drug Resistant Enterococci, Ayesha Khan

Dissertations and Theses (Open Access)

Antibiotic resistance is a major global public health threat. Enterococci are recalcitrant, nosocomial pathogens that can be intrinsically resistant to valuable antibiotics, like beta-lactams, or evolve resistance to all existing antimicrobials. The LiaFSR system regulates resistance to cell membrane (CM) stressors like daptomycin (DAP), a front-line drug for multi-drug resistant infections. DAP resistance (DAP-R) in E. faecalis is mediated by CM phospholipid alterations. Emergence of DAP-R often leads to b-lactam resensitization, a phenomenon called the seesaw effect. The molecular mechanism of DAP-R and the seesaw effect are unknown. Here we show that LiaX is a surface exposed protein whose C-terminal …

Factors That Impact Uptake Of Carrier Screening By Male Reproductive Partners Of Female Prenatal Patients, Wendi Betting

Dissertations and Theses (Open Access)

Carrier screening is a genomic technology that is used to identify individuals who are carriers of autosomal recessive conditions. Despite published recommendations, the majority of male partners do not complete carrier screening after their female partner is identified to be a carrier. Previous studieshave examined reasons why women elect or decline carrier screening, but there have been few published studies that examine factors that influence a male partner’s decision to elect or decline carrier screening, particularly when the female has been identified as a carrier. The aim of the study was to determine the factors that influence the uptake of …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

The Use Of Guedel Airway For Naso-Orogastric Tube Insertion In Patients With Covid-19. A Way To Minimize Aerosol Generation, Faraz Shafiq, Dileep Kumar

Department of Anaesthesia

No abstract provided.

Targeting Natural Killer Cells For Improved Immunity And Control Of The Adaptive Immune Response., Stephen Pierce, Eric S. Geanes, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

Natural killer (NK) cells are critical for targeting and killing tumor, virus-infected and stressed cells as a member of the innate immune system. Recently, NK cells have also emerged as key regulators of adaptive immunity and have become a prominent therapeutic target for cancer immunotherapy and infection control. NK cells display a diverse array of phenotypes and function. Determining how NK cells develop and are regulated is critical for understanding their role in both innate and adaptive immunity. In this review we discuss current research approaches into NK cell adaptive immunity and how these cells are being harnessed for improving …

Development Of Rationally Designed Live Attenuated Vaccines For Lassa Fever And Venezuelan Equine Encephalitis., Dylan Macgregor Johnson

Electronic Theses and Dissertations

Lassa Virus (LASV) and Venezuelan Equine Encephalitis Virus (VEEV) are two single stranded RNA viruses belonging to the Arenavirus and Alphavirus families, respectively. Both are emerging pathogens without approved vaccines or treatments. VEEV is an important biothreat pathogen because it has been weaponized and is extremely infectious as an aerosol. VEEV causes biphasic febrile illness that can progress to a viral encephalitis with low mortality, but high morbidity. LASV causes a viral hemorrhagic fever, Lassa Fever (LF), which is endemic in West Africa, and responsible for between 100-500k annual infections with a 1-2% overall mortality rate. ML29 and VEEV TC-83 …

Neurological Manifestations Of Covid-19, Dureshahwar Kanwar, Abdul Mannan Baig, Mohammad Wasay

Section of Neurology

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most …

Rational And Practical Use Of Imaging In Covid-19 Pneumonia, Saba Sohail

Department of Radiology

The severe form of the COVID-19 pandemic caused by the SARS-CoV-2 virus, has largely manifested as a predominant respiratory illness causing severe pneumonia characterized by bilateral, subpleural ground glass haze, progressing to consolidation, and fibrosis on imaging. There is some discrepancy between the governmental guidelines, professional Societies and Radiology and Respiratory Medicine specialists with divided opinions between the use of the chest X-rays and CT scan, and whether the use be screening or diagnostic. So far, the most balanced recommendations have been proposed by the Fleischner Society, which are endorsed by the Radiological Society of Pakistan as well. This writeup …

Elective Abdominal Aortic Aneurysm Repair Complicated With Chylous Ascites, Zia Ur Rehman

Department of Surgery Docs

No abstract provided.

The Effect Of Staphylococcus Aureus Exposure On White-Tailed Deer Trabecular Bone Stiffness And Yield, Emily Brooke Long

Graduate Theses

Osteomyelitis is an infection of the bone or bone marrow caused by the infiltration of bacteria, resulting in destructive inflammation, bone necrosis and abnormal bone remolding. With a growing number of osteomyelitis diagnoses, many of which are linked to Staphylococcus aureus (S. aureus), it is imperative to understand the pathology of S. aureus in relation to bone to provide better diagnostics and patient care. While the cellular mechanisms of S. aureus and osteomyelitis have been studied, little information exists on the biomechanical effects of such infections. We postulated that exposure to S. aureus for 72 hours would significantly decrease both …

Associations Of Sickness Absence For Pain In The Low Back, Neck And Shoulders With Wider Propensity To Pain, David Coggon, Georgia Ntani, Karen Walker-Bone, Vanda E. Felli, Raul Harari, Lope H. Barrero, Sarah A. Felknor, Marianela Rojas, Anna Cattrell, Muhammad Masood Kadir

Community Health Sciences

Objectives: To explore the association of sickness absence ascribed to pain at specific anatomical sites with wider propensity to musculoskeletal pain.
Methods: As part of the CUPID (Cultural and Psychosocial Influences on Disability) study, potential risk factors for sickness absence from musculoskeletal pain were determined for 11 922 participants from 45 occupational groups in 18 countries. After approximately 14 months, 9119 (78%) provided follow-up information about sickness in the past month because of musculoskeletal pain, including 8610 who were still in the same job. Associations with absence for pain at specific anatomical sites were assessed by logistic regression and summarised …

Forecasting The Essential Chemotherapy Needed For Treatment Of Children With Acute Lymphoblastic Leukemia In Low- And Middle-Income Countries, Brian T. Lewis

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with contemporary therapy resulting in a 90% survival in high-income countries (HIC). However, an estimated 89% of the world’s children live in low- and middle-income countries (LMIC) where survival is much lower. Lack of access to essential chemotherapy contributes significantly to the decreased survival rates for LMIC, and inaccurate forecasting of chemotherapy needed may lead to stockouts or oversupply. This chapter describes a simple forecasting system with population and patient-based multipliers for each drug used in the treatment of pediatric ALL, thus estimating the essential chemotherapy quantities needed for a …

In Vitro Bioactivities Of Single Or Combined Extracts From Three Selected Asian Vegetables, Mahmud Norfaizah

Student Works (2020-2029)

Three underutilized folklore oriental-based vegetables Acalypha indica (AI), Centella asiatica (CA), and Sesbania grandiflora (SG) have been investigated for pharmacological activities relevant to wound healing process and synergistic actions. Single and combination of aqueous (A) and methanol (M) extracts of the three vegetables namely AI-A, CA-A, SG-A, AI-M, CA-M, SG-M, AI-A+CA-A, AI-A+SG-A, CA-A+SG-A, AI-M+CA-M, AI-M+SG-M, and CA-M+SG-M were assessed for stimulation of wound closure by normal human dermal fibroblast (NHDF) cells, antioxidant, protection against hydrogen peroxide (H2O2), stimulation of nitric oxide (NO) from RAW264.7 macrophages and antimicrobial activities. The combined vegetable extracts AI-A+CA-A (90.76%) showed the highest percentage of wound …

A Replication And Extension Of A Prediction Tool Identifying Need For Treatment Among Opioid Exposed Infants, Loni Parrish

Electronic Theses and Dissertations

The incidences of maternal opioid use and neonatal opioid withdrawal syndrome (NOWS) have increased by nearly 400% over the past decade. Isemann and colleagues (2017) developed prediction tools (TiTE/TiTE²) to differentiate, within the first two days of life, between infants who will require pharmacotherapy for NOWS from those infants who will not require pharmacotherapy for NOWS. The goal of the current experiment was to replicate and extend their prediction model. The present experiments successfully replicated Isemann et al., (2017) results and also established alternative cutoff values for requiring treatment that provide better balance between all four metrics. Moreover, …

Potential Barriers Amongst Health Care Professionals Of Pakistan In Managing Covid-19 Patients, Muhammad Irfan Ul Haq, Faraz Shafiq, Haris Sheikh

Department of Anaesthesia

Objectives: To evaluate basic knowledge of Health Care Professionals (HCPs) of Pakistan in managing COVID 19 patients. It includes information regarding infection control measures, administrative and professional support. This was followed by evaluation of psychological factor that can act as a barrier in effective management of these patients.
Methods: The survey was conducted on line using Google Form. After approval from hospital ethical committee survey link was disseminated to HCPs using social media.
Results: Four hundred fifteen HCPs were participated. Most of them were younger than 30 years and majority of them were postgraduate trainees. Results showed gaps in the …

Ape1 Promotes Pancreatic Cancer Proliferation Through Gfrα1/Src/Erk Axis-Cascade Signaling In Response To Gdnf, Yoo-Duk Choi, Ji-Yeon Jung, Minwoo Baek, Sheema Khan, Peter I. Song, Sunhyo Ryu, Joo-Yeon Koo, Subhash C. Chauhan, Andrew Tsin, Chan Choi, Won Jae Kim, Mihwa Kim

School of Medicine Publications

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

The Emerging Oral Pathogen, Filifactor Alocis, Disrupts Neutrophil Functions To Enhance Survival And Dysregulate Inflammation., Irina Miralda Molina

Electronic Theses and Dissertations

Periodontitis is an irreversible, chronic inflammatory disease where pathogenic microbial communities accumulate in the gingival crevice. Advances in culture-independent techniques have facilitated the identification of new bacterial species in periodontal lesions, such as the Gram-positive anaerobe, Filifactor alocis. Neutrophils are a major component of the innate host response, and the outcome of their interaction with F. alocis may be a determinant of oral health status. While neutrophil functions typically protect the host against periodontal disease, oral pathogens have adapted to evade or disarm neutrophil microbicidal functions while promoting mechanisms that drive inflammation, which also provides a source of nutrients …

Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …

Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle

Electronic Theses and Dissertations

BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …

Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson

Electronic Theses and Dissertations

Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …

Polysubstance Exposure And Its Relationship To Pharmacological Treatment Characteristics, Parker Miller

Undergraduate Honors Theses

Neonatal Abstinence Syndrome (NAS) remains an ever-growing public health issue and a continued avenue for future research. The research question for this retrospective study was whether polysubstance exposure is related to the dose of medication the infant received or to the number of opioid-medications required to treat the infants’ withdrawal symptoms? The hypothesis for the retrospective study was there will be a significant relationship between polysubstance exposure and the dose of medication the infant received as well as the number of opioid-medications required to treat the infants’ withdrawal symptoms. A bivariate correlational indicated that there was not a significant association …

Evaluation Of Anthelmintic Therapies In A Fall Calving Beef Cowherd, Laine Zammit

Graduate Theses and Dissertations

Internal parasitism inevitability prompts economic loss in beef cattle production by decreasing growth performance and reproductive traits. Today, the most widely used class of anthelmintic used to treat parasitism, is the macrocyclic lactone. Many studies have conflicting results on the efficacy of macrocyclic lactones (ML) efficacy against internal parasitism. The objective of this study was to evaluate the effectiveness of moxidectin and eprinomectin, two of the MLs, on cow performance. Multiparous fall calving, crossbred beef cows (n = 106) were allocated randomly to 1 of 3 anthelmintic treatments: 1) Negative control (CON), in which cows did not receive an anthelmintic, …

Radiology Of Covid-19 - Imaging The Pulmonary Damage, Saba Sohail

Department of Radiology

A large part of the world is presently in the grip of the coronavirus disease (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), declared a pandemic in March 2020. This document is a brief commentary of the imaging modalities used in the screening, diagnosis and management of COVID-19 pneumonia. Chest x-rays, especially portable, still form a part of majority of official guidelines, with reports of the suggestive radiologic features. The potential of CT scan and ultrasound is also realised, with earlier detection rate. Typical radiologic findings of bilateral, asymmetrical, crazy-paved ground glass opacification, consolidation, reverse halo sign, opacities, …

Clinical Features, Diagnosis And Management Of Covid-19 Patients In The Outdoor Setting, Bushra Jamil

Department of Medicine

In a brief span of a few months, coronavirus disease (COVID-19) pandemic has brought a major paradigm shift in operation of clinical services around the world. Infection may be mild, moderate or severe; many remain asymptomatic. High burden of non-communicable and communicable diseases theoretically puts Pakistani population at increased risk of severe COVID-19 infection. Considering the universal risk of infection, the outpatient services in Pakistan need to be redesigned. Starting with risk assessment of the facility and provision of a dedicated telephone connection, structure and workflow need to be redesigned in order to minimise risk of exposure to healthcare professionals, …

Impact Of Slco1b1 Genetic Variation On Rosuvastatin Systemic Exposure In Pediatric Hypercholesterolemia., Jonathan B. Wagner, Susan M. Abdel-Rahman, Andrea Gaedigk, R Gaedigk, Geetha Raghuveer, Vincent S. Staggs, Leon Van Haandel, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

This study investigated the impact of SLCO1B1 genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 13; 521CC, n = 2) and wild type controls (521TT, n = 13) completed a single oral dose pharmacokinetic study. The variability contributed by SLCO1B1 c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration-time curve from 0-24 hours (AUC

Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding

Faculty, Staff and Student Publications

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear.

OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways.

METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet …

Unique Case Of Anca-Negative Pauci-Immune Necrotizing Glomerulonephritis With Diffuse Alveolar Hemorrhage, Potentially Associated With Midostaurin, Jaya Kala

Faculty, Staff and Student Publications

We present a 61-year-old male with FLT3-mutated acute myeloid leukemia treated with midostaurin who developed acute kidney injury requiring hemodialysis and pulmonary renal syndrome. Antibodies to proteinase-3, myeloperoxidase, and glomerular basement membrane were negative. Renal biopsy confirmed acute pauci-immune focal necrotizing glomerulonephritis (GN) with fibrin crescents indicating rapidly progressing glomerulonephritis. He improved with pulse methylprednisolone, intravenous cyclophosphamide, and plasma exchange with resolution of hemoptysis. This case highlights the importance of prompt renal biopsy to guide early initiation of life-saving therapies. To our knowledge, this is the first reported case of ANCA-negative pauci-immune necrotizing GN likely secondary to midostaurin.

Surgical Management And Outcome Of Newly Diagnosed Glioblastoma Without Contrast Enhancement (Low-Grade Appearance): A Report Of The Rano Resect Group

Faculty, Staff and Student Publications

The palatomaxillary structure plays critical roles in both form and function of the midface. Surgical defects of the palate and maxilla can be associated with significant morbidity and deformity. Various defect classification systems have been used to assist in reconstruction and rehabilitation. Reconstructive options include prosthetic rehabilitation, local flaps, and free tissue transfer. Here, we review the functional and surgical anatomy of the palatomaxillary complex, defect classification systems, and provide an overview of reconstructive options.

Calcitonin Prescribing Criteria For The Management Of Hypercalcemia In A Community Hospital, Jessica Hernandez, Radhan Gopalani, Heidi Clarke, Joyce Lee, Alyssa Donadio

All Publications

Purpose/Background: Hypercalcemia is a clinical condition in which serum calcium levels exceed the upper limit of normal (>10.5 mg/dL). The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy, however, it can also be caused by vitamin D intoxication, endocrine disorders, and immobilization due to an increase in bone resorption. First-line treatment of hypercalcemia includes hydration with intravenous (IV) normal saline and IV bisphosphonates. Calcitonin (Miacalcin®) is a synthetic hormone with a rapid onset of action and used intramuscularly (IM) or subcutaneously (SQ) as a second-line treatment in the management of hypercalcemia, specifically in severe and in symptomatic …