Diseases Commons^™

The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.

METHODOLOGY: MicroRNAs (miRNAs) and other …

Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake

Honors Scholar Theses

Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating …

Role Of Smarce1 And Bhlhe40 In Breast Cancer Metastasis, Aarti Sethuraman

Theses and Dissertations (ETD)

No abstract provided.

In-Vitro Simulation Of Acute Ischemic Stroke, Paolo Garcia

Biomedical Engineering Undergraduate Honors Theses

Acute ischemic stroke (AIS) is a condition that involves the occlusion of a blood vessel within the brain, effectively preventing the passage of oxygen and nutrients. AIS is highly prevalent in the United States, where nearly 795,000 strokes happen per year and 87% of those are ischemic. From a medical standpoint, the obstructing clot can be removed with the use of a stroke retrieval device. However, a need arises for testing the aforementioned devices on a patient’s specific vascular geometries in order to increase the likelihood of a successful procedure. Outlined is a process for developing a physical simulation of …

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

Can Alcaligenes Be A New Treatment For Staphylococcus Species?, Devin Narwani

Undergraduate Honors Theses

Members of the Staphylococcus genus are known to cause serious human infections in the clinical environment. Many species of this genus are typically found among the normal flora of the skin, nasal cavities, and the linings of the throat; however, the bacterium becomes an opportunistic infection when there is a break in the physical barriers or when a contaminated medical device is implanted in the human body. As more resistant strains are beginning to appear it is becoming drastically harder to treat patients infected with this bacterium. One such strain is Methicillin Resistant Staphylococcus aureus (MRSA). MRSA is a major …

The Inhibitory Effects Of A Novel Gel On Staphylococcus Aureus Biofilms, Lindsey Vance

Undergraduate Honors Theses

Antibiotic resistance is an ever-growing topic of concern within the medical field causing researchers to examine the mechanisms of resistance to develop new antimicrobials. Bacteria’s ability to form biofilms is one mechanism which aids in antimicrobial resistance. Staphylococcus aureus is of special interest as it is one of the most frequent biofilm-forming bacteria found on medical devices causing infections and posing dangerous threats in a clinical setting. A recently developed antimicrobial gel has been shown to have profound effects on treating bacterial infections and wound healing. This research is centered upon examining the antimicrobial effects of this gel on the …

Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best

Electronic Theses and Dissertations

Legionella pneumophila is an environment organism that parasitizes a wide range of protozoa. Growth within the environmental host primes L. pneumophila for infection of human alveolar macrophages when contaminated aerosols are inhaled. Intracellular replication within either host requires the establishment a replicative niche, known as the Legionella-containing vacuole (LCV). Biogenesis of the LCV depends on the type IVb translocation system, the Dot/Icm, to translocation >320 effectors into the host cytosol. Effectors are responsible for preventing lysosome fusion to the LCV, recruitment of ER-derived vesicles to the LCV, and modulation of a plethora of host processes to promote the intracellular …

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

Investigation Into The Role Of Platelet Derived Growth Factor (Pdgf) In Type I Collagen Glomerulopathy, Isaac C. Springer

Graduate Theses/Dissertations

Progressive accumulation of collagen and extracellular matrix (ECM) proteins within renal glomeruli have implications for or result in renal fibrosis and glomerulosclerosis, with both events culminating in renal failure. To model this accumulation the Col1a2-deficient mouse model was used. The Col1a2-deficientmouse model is characterized by a mutation in the a2(I) chain, preventing incorporation into the type I collagen molecule. As a result, an α1(I) collagen chain incorporates into the collagen triple helix forming homotrimeric type I collagen, as opposed to heterotrimeric type I collagen. This change is due to the secondary wound healing response in response to ECM accumulation, …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Outcomes Of Genetic Testing In A Genitourinary Genetics Clinic, Annelise Pace

Dissertations and Theses (Open Access)

Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU-related hereditary cancer syndromes but there is limited research on the clinical picture of these patients, including their cancerous and non-cancerous features, the genetic testing strategy for this population, and the probability of having a positive germline mutation if testing is performed. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate whether there is a relationship between the indication for genetic testing …

Bioprospecting Deep-Sea Actinobacteria For Novel Anti-Infective Natural Products, Dongbo Xu, Linna Han, Chunhui Li, Qi Cao, Duolong Zhu, Nolan H. Barrett, Dedra Harmody, Jing Chen, Haining Zhu, Peter J. Mccarthy, Xingmin Sun, Guojun Wang

Molecular and Cellular Biochemistry Faculty Publications

The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. More than half of the tested strains (27) were identified as …

Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas

Senior Honors Theses

Shingles, the disease caused by the herpes zoster virus, is a widespread and widely misunderstood illness in the United States. It is preventable, but many at-risk patients do not know what measures they may take to prevent it. Clear communication from physician to patient is crucial for patient understanding of diseases. Many patient education materials on herpes zoster currently available are often unused. It is therefore beneficial to public health to disseminate new mediums of medical communication, and one way of accomplishing this is through adult coloring books. The pathophysiology of herpes zoster virus is here explored and the idea …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

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 …

Chemiluminescent Agents For In Vivo Imaging, Jian Cao

Chemistry Theses and Dissertations

Chemiluminescence is the light production directly from a highly exothermic chemical reaction by generating electronically excited species, and the light will be generated upon relaxation to the ground state. We utilize this light as the readout to construct imaging agents for reactive species. Chemiluminescence as an imaging modality has many advantages compared with current widely used imaging modalities, such as fluorescence and bioluminescence. The main advantages are the elimination of extraneous light excitation or genetic modification, which are required for fluorescence and bioluminescence imaging. Therefore, chemiluminescence as a imaging modality holds great potential for in vivo imaging.

In this dissertation, …

Microbial Co-Infection Alters Macrophage Polarization, Phagosomal Escape, And Microbial Killing, Nikita H. Trivedi, Jieh-Juen Yu, Chiung-Yu Hung, Richard P. Doelger, Christopher S. Navara, Lisa Y. Armitige, Janakiram Seshu, Anthony P. Sinai, James P. Chambers, M. Neal Guentzel, Bernard P. Arulanandam

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection. Non-activated (M0) macrophages or activated M2-polarized cells (J774 cells transfected with the mouse IL-4 gene) were first infected with BCG for …

Clinical-Evolutional Particularities Of The Cryoglobulinemic Vasculitis In The Case Of A Patient Diagnosed With Hepatitis C Virus In The Predialitic Phase, Daniel C. Caragea, Larisa Săndulescu, Vlad Pădureanu, Mircea C. Forțofoiu, Costin Streba, Lidia Boldeanu, Mihail V. Boldeanu, Mircea Popescu-Drigă, Marius E. Ciurea, Maria Forțofoiu, Ion Rogoveanu, Tudorel Ciurea, Cristin C. Vere

Journal of Mind and Medical Sciences

Hepatitis C virus (HCV) represents a fundamental issue for public health, with long term evolution and the gradual appearance of several complications and associated pathologies. One of these pathologies is represented by cryoglobulinemic vasculitis, a disorder characterized by the appearance in the patient’s serum of the cryoglobulins, which typically precipitate at temperatures below normal body temperature (37°C) and dissolve again if the serum is heated. Here, we describe the case of a patient diagnosed with HCV that, during the evolution of the hepatic disease, developed a form of cryoglobulinemic vasculitis. The connection between the vasculitis and the hepatic disorder was …

Melatonin Attenuates Oxidative Stress And Modulates Inflammatory Response After Experimental Burn Trauma, Minka Hristova, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva

Journal of Mind and Medical Sciences

Introduction. Thermal injury activates an inflammatory response. Melatonin possesses anti-oxidant and anti-inflammatory properties. The objective of the present work was to study melatonin effects on the inflammatory response under conditions of oxidative stress during the early stage of thermal injury.

Materials and methods. We used 24 white male rats of Wistar breed, randomly divided into three experimental groups. Group one was the control, group two was inflicted with burn trauma, and group three was inflicted with burn trauma, with melatonin application following the thermal injury. Melatonin was applied twice in doses of 10 g/kg b.m. immediately after the burn trauma …

Dietary Habits And Lifestyle In School-Aged Children From Bucharest, Romania, Anca Pantea Stoian, Liliana F. Andronache, Razvan Hainarosie, Dan N. Paduraru, Cristinel D. Badiu, Andreea Arsene, Claudia Mehedintu, Georgiana Ditu, Silviu M. Pituru, Cristina Orlov, Mihaela Oros, Cornelia Nitipir

Journal of Mind and Medical Sciences

Background. This study evaluated the difference between boys and girls in terms of nutritional status, lifestyle, and dietary habits during school life.

Materials and Methods. A descriptive and observational study was conducted in 2016, in which 251 children, aged 7-17, from 3 elementary schools and a high school inBucharest,Romania, were evaluated. A questionnaire was used to assess food behavior, eating, and lifestyle habits.

Results. Boys had a significantly higher waist circumference (71.18±9) than girls (67.46±9.91) (p=0.004). Thus 27% of boys were overweight or obese compared with only 22% of the girls. Differences were also seen between the two groups in …

Vascular Neurocognitive Disorders And The Vascular Risk Factors, Carmen V. Albu, Vlad Padureanu, Mihail V. Boldeanu, Ana M. Bumbea, Anca S. Enescu, Dana M. Albulescu, Cristian A. Silosi, Aurelia Enescu

Journal of Mind and Medical Sciences

Dementias are clinical neurodegenerative diseases characterized by permanent and progressive transformation of cognitive functions such as memory, learning capacity, attention, thinking, language, passing judgments, calculation or orientation. Dementias represent a relatively frequent pathology, encountered at about 10% of the population of 65-year olds and 20% of the population of 80-year olds.

This review presents the main etiological forms of dementia, which include Alzheimer form of dementia, vascular dementia, dementia associated with alpha-synucleionopathies, and mixed forms. Regarding vascular dementia, the risk factors are similar to those for an ischemic or hemorrhagic cerebrovascular accident: arterial hypertension, diabetes mellitus, dyslipidemia, smoking, obesity, age, …

Investigating Ampk Signalling Regulation Of Autophagy In A Model Of Ovarian Tumour Dormancy, Jeremi Laski

Western Research Forum

Investigating AMPK signalling regulation of autophagy in a model of ovarian tumour dormancy

Jeremi Laski and Trevor G. Shepherd

Background:

Ovarian cancer is the most deadly gynecologic malignancy in women. A particular subset of this disease, epithelial ovarian cancer (EOC), is responsible for over 70% of all diagnosed ovarian cancer cases, yet the mechanisms governing disease progression are poorly understood. One of the unique hallmarks of EOC metastasis lies in the process of spheroid formation, whereby tumour cells aggregate into larger 3D structures. These EOC spheroids have been shown to be metabolically dormant, while concurrently up-regulating autophagy (cellular waste …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Variant Intestinal-Cell Kinase In Juvenile Myoclonic Epilepsy, J. N. Bailey, L. De Nijs, D. Bai, T. Suzuki, H. Miyamoto, M. Tanaka, C. Patterson, Y.-C. Lin, M. T. Medina, M. E. Alonso, J. M. Serratosa, R. M. Durón, Viet-Hong Nguyen, J. E. Wight, I. E. Martínez‑Juárez, A. Ochoa, A. Jara-Prado, L. Guilhoto, Y. Molina, E. M. Yacubian, M. López‑Ruiz, Y. Inoue, S. Kaneko, S. Hirose, M. Osawa, H. Oguni, S. Fujimoto, T. M. Grisar, J. M. Stern, K. Yamakawa, B. Lakaye, A. V. Delgado-Escueta

Pharmacy Faculty Articles and Research

BACKGROUND

In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.

METHODS

Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase (ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds …

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …

Aging Exacerbates Development Of Cerebral Microbleeds In A Mouse Model, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Annlia Paganini-Hill, Kelley Kilday, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age.

Methods: We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Repeat-Associated Non-Aug (Ran) Translation And Other Molecular Mechanisms In Fragile X Tremor Ataxia Syndrome, M. Rebecca Glineburg, Peter K. Todd, Nicolas Charlet-Berguerand, Chantal Sellier

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5′UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript. Here we focus on two proposed disease mechanisms for FXTAS: 1) RNA …