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Vitamin D Supplementation Among Bangladeshi Children Under-Five Years Of Age Hospitalised For Severe Pneumonia: A Randomised Placebo Controlled Trial, Fahmida Chowdhury, Abu Sadat Mohammad Sayeem Bin Shahid, Mosharrat Tabassum, Irin Parvin, Probir Kumar Ghosh, Mohammad Iqbal Hossain, Nur Haque Alam, A. S. G. Faruque, Sayeeda Huq, Lubaba Shahrin, Nusrat Homaira, Zakiul Hassan, Zubair Akhtar, S. Mah-E-Muneer, George J. Fuchs Iii, Tahmeed Ahmed, Mohammod Jobayer Chisti Feb 2021

Vitamin D Supplementation Among Bangladeshi Children Under-Five Years Of Age Hospitalised For Severe Pneumonia: A Randomised Placebo Controlled Trial, Fahmida Chowdhury, Abu Sadat Mohammad Sayeem Bin Shahid, Mosharrat Tabassum, Irin Parvin, Probir Kumar Ghosh, Mohammad Iqbal Hossain, Nur Haque Alam, A. S. G. Faruque, Sayeeda Huq, Lubaba Shahrin, Nusrat Homaira, Zakiul Hassan, Zubair Akhtar, S. Mah-E-Muneer, George J. Fuchs Iii, Tahmeed Ahmed, Mohammod Jobayer Chisti

Pediatrics Faculty Publications

INTRODUCTION: Vitamin D is important for its immunomodulatory role and there is an independent association between vitamin D deficiency and pneumonia. We assessed the effect of vitamin D supplementation on the outcome in children hospitalized for severe pneumonia.

METHODS: This was a randomised, double blinded, placebo-controlled clinical trial in children aged >2–59 months with severe pneumonia attending Dhaka Hospital, icddr,b. Children received age-specific megadose of vitamin D3 (20,000IU: < 6 months, 50,000 IU: 6–12 months, 100,000 IU:13–59 months) or placebo on first day and 10,000 IU as maintenance dose for next 4 days or until discharge (if discharged earlier) along with standard therapy. This trial is registered at ClinicalTrials.gov, number NCT02185196.

FINDINGS: We enrolled 100 children in placebo group and 97 in vitamin D group. On admission, 50 (52%) and 49 (49%) of children in vitamin D and placebo groups, respectively were vitamin …


Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola Feb 2021

Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola

Pharmaceutical Sciences Faculty Publications

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on …


An Egocentric Network Contact Tracing Experiment: Testing Different Procedures To Elicit Contacts And Places, Andrew Pilny, C. Joseph Huber Feb 2021

An Egocentric Network Contact Tracing Experiment: Testing Different Procedures To Elicit Contacts And Places, Andrew Pilny, C. Joseph Huber

Communication Faculty Publications

Contact tracing is one of the oldest social network health interventions used to reduce the diffusion of various infectious diseases. However, some infectious diseases like COVID-19 amass at such a great scope that traditional methods of conducting contact tracing (e.g., face-to-face interviews) remain difficult to implement, pointing to the need to develop reliable and valid survey approaches. The purpose of this research is to test the effectiveness of three different egocentric survey methods for extracting contact tracing data: (1) a baseline approach, (2) a retrieval cue approach, and (3) a context-based approach. A sample of 397 college students were randomized …


Piglet Immunization With A Spike Subunit Vaccine Enhances Disease By Porcine Epidemic Diarrhea Virus, Jieshi Yu, Chithra Sreenivasan, Tirth Uprety, Rongyuan Gao, Chen Huang, Ella J. Lee, Steven Lawson, Julie Nelson, Jane Christopher-Hennings, Radhey S. Kaushik, Eric Nelson, Diego G. Diel, Ben M. Hause, Feng Li, Dan Wang Feb 2021

Piglet Immunization With A Spike Subunit Vaccine Enhances Disease By Porcine Epidemic Diarrhea Virus, Jieshi Yu, Chithra Sreenivasan, Tirth Uprety, Rongyuan Gao, Chen Huang, Ella J. Lee, Steven Lawson, Julie Nelson, Jane Christopher-Hennings, Radhey S. Kaushik, Eric Nelson, Diego G. Diel, Ben M. Hause, Feng Li, Dan Wang

Maxwell H. Gluck Equine Research Center Faculty Publications

Immunization with an insect cell lysate/baculovirus mixture containing recombinant porcine epidemic diarrhea virus (PEDV) spike protein induced high levels of neutralizing antibodies in both mice and piglets. However, immunization of piglets with this vaccine resulted in enhancement of disease symptoms and virus replication in vaccine recipients exposed to PEDV challenge. Thus, these observations demonstrate a previously unrecognized challenge of PEDV vaccine research, which has important implications for coronavirus vaccine development.


Macrophage-Engineered Vesicles For Therapeutic Delivery And Bidirectional Reprogramming Of Immune Cell Polarization, Khaga R. Neupane, J. Robert Mccorkle, Timothy J. Kopper, Jourdan E. Lakes, Surya P. Aryal, Masud Abdullah, Aaron A. Snell, John C. Gensel, Jill M. Kolesar, Christopher I. Richards Jan 2021

Macrophage-Engineered Vesicles For Therapeutic Delivery And Bidirectional Reprogramming Of Immune Cell Polarization, Khaga R. Neupane, J. Robert Mccorkle, Timothy J. Kopper, Jourdan E. Lakes, Surya P. Aryal, Masud Abdullah, Aaron A. Snell, John C. Gensel, Jill M. Kolesar, Christopher I. Richards

Spinal Cord and Brain Injury Research Center Faculty Publications

Macrophages, one of the most important phagocytic cells of the immune system, are highly plastic and are known to exhibit diverse roles under different pathological conditions. The ability to repolarize macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) or vice versa offers a promising therapeutic approach for treating various diseases such as traumatic injury and cancer. Herein, it is demonstrated that macrophage-engineered vesicles (MEVs) generated by disruption of macrophage cellular membranes can be used as nanocarriers capable of reprogramming macrophages and microglia toward either pro- or anti-inflammatory phenotypes. MEVs can be produced at high yields and easily loaded with diagnostic molecules …


Tomato Chlorosis Virus Infection Facilitates Bemisia Tabaci Med Reproduction By Elevating Vitellogenin Expression, Liping Huang, Xiaobin Shi, Jizhe Shi, Zhuo Zhang, Yong Fang, Zhanhong Zhang, Qiuyi Pan, Limin Zheng, Yang Gao, Deyong Zhang, Xinqiu Tan, Yong Liu, Xuguo Zhou Jan 2021

Tomato Chlorosis Virus Infection Facilitates Bemisia Tabaci Med Reproduction By Elevating Vitellogenin Expression, Liping Huang, Xiaobin Shi, Jizhe Shi, Zhuo Zhang, Yong Fang, Zhanhong Zhang, Qiuyi Pan, Limin Zheng, Yang Gao, Deyong Zhang, Xinqiu Tan, Yong Liu, Xuguo Zhou

Entomology Faculty Publications

Transmission of plant pathogenic viruses mostly relies on insect vectors. Plant virus could enhance its transmission by modulating the vector. Previously, we showed that feeding on virus infected plants can promote the reproduction of the sweet potato whitefly, Bemisia tabaci MED (Q biotype). In this study, using a whitefly-Tomato chlorosis virus (ToCV)-tomato system, we investigated how ToCV modulates B. tabaci MED reproduction to facilitate its spread. Here, we hypothesized that ToCV-infected tomato plants would increase B. tabaci MED fecundity via elevated vitellogenin (Vg) gene expression. As a result, fecundity and the relative expression of B. tabaci MED Vg …


Poll Finds Rural Residents More Hesitant To Get Vaccinated, Tim Marema Jan 2021

Poll Finds Rural Residents More Hesitant To Get Vaccinated, Tim Marema

Journal of Appalachian Health

Rural residents are more hesitant than their metropolitan counterparts to get a Covid-19 vaccination, even though rural areas have higher rates of infections and deaths from the coronavirus.


High-Density Lipoproteins And Serum Amyloid A (Saa), Nancy R. Webb Jan 2021

High-Density Lipoproteins And Serum Amyloid A (Saa), Nancy R. Webb

Pharmacology and Nutritional Sciences Faculty Publications

PURPOSE OF REVIEW: Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL.

RECENT FINDINGS: Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of …


Encephalopathy And Complex Hyperkinesia In A Patient With Severe Acute Respiratory Syndrome Coronavirus-2 Infection, Wenyang Li, Elif Pinar Coskun, Rolando Berger, John T. Slevin, L. Creed Pettigrew Jan 2021

Encephalopathy And Complex Hyperkinesia In A Patient With Severe Acute Respiratory Syndrome Coronavirus-2 Infection, Wenyang Li, Elif Pinar Coskun, Rolando Berger, John T. Slevin, L. Creed Pettigrew

Neurology Faculty Publications

No abstract provided.


Sex Differences And Psychological Stress: Responses To The Covid-19 Pandemic In China, Shiyan Yan, Rui Xu, Terry D. Stratton, Voyko Kavcic, Dan Luo, Fengsu Hou, Fengying Bi, Rong Jiao, Kangxing Song, Yang Jiang Jan 2021

Sex Differences And Psychological Stress: Responses To The Covid-19 Pandemic In China, Shiyan Yan, Rui Xu, Terry D. Stratton, Voyko Kavcic, Dan Luo, Fengsu Hou, Fengying Bi, Rong Jiao, Kangxing Song, Yang Jiang

Behavioral Science Faculty Publications

BACKGROUND: About 83,000 COVID-19 patients were confirmed in China up to May 2020. Amid the well-documented threats to physical health, the effects of this public health crisis - and the varied efforts to contain its spread - have altered individuals' "normal" daily functioning. These impacts on social, psychological, and emotional well-being remain relatively unexplored - in particular, the ways in which Chinese men and women experience and respond to potential behavioral stressors. Our study investigated sex differences in psychological stress, emotional reactions, and behavioral responses to COVID-19 and related threats among Chinese residents.

METHODS: In late February (2020), an anonymous …


Modes Of Transmission Of Severe Acute Respiratory Syndrome-Coronavirus-2 (Sars-Cov-2) And Factors Influencing On The Airborne Transmission: A Review, Mahdieh Delikhoon, Marcelo I. Guzman, Ramin Nabizadeh, Abbas Norouzian Baghani Jan 2021

Modes Of Transmission Of Severe Acute Respiratory Syndrome-Coronavirus-2 (Sars-Cov-2) And Factors Influencing On The Airborne Transmission: A Review, Mahdieh Delikhoon, Marcelo I. Guzman, Ramin Nabizadeh, Abbas Norouzian Baghani

Chemistry Faculty Publications

The multiple modes of SARS-CoV-2 transmission including airborne, droplet, contact, and fecal–oral transmissions that cause coronavirus disease 2019 (COVID-19) contribute to a public threat to the lives of people worldwide. Herein, different databases are reviewed to evaluate modes of transmission of SARS-CoV-2 and study the effects of negative pressure ventilation, air conditioning system, and related protection approaches of this virus. Droplet transmission was commonly reported to occur in particles with diameter >5 µm that can quickly settle gravitationally on surfaces (1–2 m). Instead, fine and ultrafine particles (airborne transmission) can stay suspended for an extended period of time (≥2 h) …


Monocyte Abundance And White Blood Cell Expression Of Prolactin And Nf-Kb Pathway Genes In Beef Steers Are Altered By Grazing Toxic Endophyte-Infected Tall Fescue And Lipopolysaccharide Challenge, Cecilia Winfrey Jan 2021

Monocyte Abundance And White Blood Cell Expression Of Prolactin And Nf-Kb Pathway Genes In Beef Steers Are Altered By Grazing Toxic Endophyte-Infected Tall Fescue And Lipopolysaccharide Challenge, Cecilia Winfrey

Theses and Dissertations--Animal and Food Sciences

Experiment 1 tested the hypothesis that ad libitum consumption of a 1:1 blend (MIX) of sodium selenite (ISe) and SELPLEX vs solely ISe as selenium (Se) supplements (27 ppm) in a vitamin-mineral mix (V-M) by steers subjected to summer-long grazing of toxic endophyte-infected tall fescue (TE) would ameliorate the negative effects of TE by positively affecting the expression pattern of prolactin (PRL) and NF-kB pathway genes by circulating leukocytes (WBC). Experiment 2 tested the hypothesis that the MIX form of supplemental Se also would ameliorate the negative effects of in vitro blood lipopolysaccharide challenge (LPS) on WBC gene expression. The …


Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic Jan 2021

Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic

Theses and Dissertations--Epidemiology and Biostatistics

The incidence of melanoma and lung cancer has been gradually increasing in the United States over the past three decades with the reputed causes due to etiological and environmental exposures, and tobacco usage. There has been concern that melanoma and lung cancer incidence among military personnel may be associated with deployment to environments with intense sun exposure and increased smoking rates due to post-traumatic stress disorder. The aim of this study was to examine associations between deployment in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), from 2001 through 2015, with subsequent melanoma and lung cancer incidence. …


Teeka Tehreek: Increasing Epi Vaccinations In Khyber Pakhtunkhwa, Pakistan, Narjis Fatima Hussain Jan 2021

Teeka Tehreek: Increasing Epi Vaccinations In Khyber Pakhtunkhwa, Pakistan, Narjis Fatima Hussain

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Globally, Pakistan ranks third among countries with the most unvaccinated and under-vaccinated children. Within the country, there are huge regional disparities, and the Khyber Pakhtunkhwa region (KPK FATA) has one of the lowest vaccination rates in the country. Low vaccination rates contribute to the high burden of childhood infectious diseases in Pakistan that cause 70% of childhood deaths. Addressing the issue requires an understanding of the barriers towards vaccinations; 30% of refusals are due to religious reasons and other misconceptions that are compounded by low literacy rates. Since religion has a critical authority in shaping the population’s beliefs, attitudes, …


Novel Machine Learning And Wearable Sensor Based Solutions For Smart Healthcare Monitoring, Rajdeep Kumar Nath Jan 2021

Novel Machine Learning And Wearable Sensor Based Solutions For Smart Healthcare Monitoring, Rajdeep Kumar Nath

Theses and Dissertations--Electrical and Computer Engineering

The advent of IoT has enabled the design of connected and integrated smart health monitoring systems. These health monitoring systems can be utilized for monitoring the mental and physical wellbeing of a person. Stress, anxiety, and hypertension are the major elements responsible for the plethora of physical and mental illnesses. In this context, the older population demands special attention because of the several age-related complications that exacerbate the effects of stress, anxiety, and hypertension. Monitoring stress, anxiety, and blood pressure regularly can prevent long-term damage by initiating necessary intervention or clinical treatment beforehand. This will improve the quality of life …


Prevalence And Correlates Of Secondary Syringe Exchange (Sse) Among People Who Inject Drugs (Pwid) In Rural Kentucky, Jordan R. Wilson Jan 2021

Prevalence And Correlates Of Secondary Syringe Exchange (Sse) Among People Who Inject Drugs (Pwid) In Rural Kentucky, Jordan R. Wilson

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Aim: To describe the prevalence of secondary syringe exchange (SSE) in a sample of syringe service program (SSP) clients in rural Appalachian Kentucky and to identify the correlates of SSE.

Methods: Participants (n=338) completed interviewer-administered questionnaires. Only those who reported having ever exchanged syringes at a SSP (n=140) were included in analysis. SSE was measured through self-report of obtaining syringes for someone else at a SSP in the past 6 months. Prevalence and correlates of SSE were examined using bivariate analysis and multiple logistic regression.

Results: Overall, 30% of participants reported SSE. Participants in the second [aOR= 3.83; 95% CI: …


Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley Jan 2021

Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

BACKGROUND/ OBJECTIVE: Cervical cancer is the fourth most commonly occurring malignancy in women worldwide, with an estimated 530,000 new cases and 270,000 new deaths each year (Small et al, 2017). While the incidence of cervical cancer has decreased by approximately 1.9% per year between 2007 and 2011, the death rate has remained stable (Bernard et al, 2014). Studies have shown that nearly all cervical cancer cases are associated with the Human Papilloma Virus (HPV). Many studies support the association of smoking with increased risk of invasive cervical cancer in women with high-risk HPV (Castle et al, 2002; Fang et al, …


Methenamine Prophylaxis For Recurrent Urinary Tract Infections In A Tertiary Referral Center, Cameron A. Wade Jan 2021

Methenamine Prophylaxis For Recurrent Urinary Tract Infections In A Tertiary Referral Center, Cameron A. Wade

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Purpose: Methenamine hippurate (MH) is a urinary antiseptic, indicated for prophylaxis of recurrent urinary tract infections (UTIs) but with only few and limited studies regarding its efficacy. To help address this knowledge gap we reviewed our experience with MH for UTI prophylaxis, focusing on women with recurrent uncomplicated UTIs.

Materials and Methods: The University of Kentucky electronic health record was queried to identify adults who were prescribed MH from the Urology clinic between January 2013 and January 2019. Charts were reviewed to assess patient-reported UTI frequency, demographics and relevant health factors. Treatment success was defined as 0-1 UTI in 6 …


Healthy Living People: A Hiv Transmission Intervention In Four Chicago Communities, Angela Wuerger Jan 2021

Healthy Living People: A Hiv Transmission Intervention In Four Chicago Communities, Angela Wuerger

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The transmission of HIV within the city of Chicago has been established as a major health concern: however, the lack of adequate resources has created gaps within current programming available for people living with HIV. Healthy Living People (HLP) is an evidence-based program focused on reducing the transmission of HIV through strengthening adherence to antiretroviral therapy and decreasing number of higher risk sexual encounters. The Chicago Department of Public Health will provide the HLP program, which includes fifteen 90-minute sessions over the course of one year. The HLP program will be offered for people living with

HIV in four Chicago …


Rabies In Kentucky From 1989-2020: A Case For Surveillance, Sarah Jane Robbins Jan 2021

Rabies In Kentucky From 1989-2020: A Case For Surveillance, Sarah Jane Robbins

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The Kentucky rabies reporting system includes data from five laboratories and provides an account of suspected rabies reports since 1989. Over 35,000 suspected cases are used to estimate rabies incidence temporally and spatially. Recommendations to the current rabies reporting methodologies are presented through proposed innovations of a standard, electronic reporting form. Given the multiple sources of data, the reporting system lacks standardization and comprehensive information about suspected rabies events, resulting in limited epidemiological capabilities; and data issues that prevent its use as a surveillance system. These issues are a limiting factor in rabies elimination; but a driving factor in over-testing, …


Mitigating Opioid Related Healthcare Use In Kentucky: An Assessment Of The Impact Of Kentucky Revised Statute (Krs) Changes To Opioid Prescribing On Opioid Related Prescribing And Healthcare Utilization, Drew Speer Jan 2021

Mitigating Opioid Related Healthcare Use In Kentucky: An Assessment Of The Impact Of Kentucky Revised Statute (Krs) Changes To Opioid Prescribing On Opioid Related Prescribing And Healthcare Utilization, Drew Speer

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The opioid epidemic has impacted few other places more than the state of Kentucky. In 2018, data from the Centers of Disease Control and Prevention (CDC) and the National Institute on Drug Abuse (NIDA) ranked Kentucky as being in the top ten for rate of drug overdose deaths and opioid-involved overdose deaths per 100,000 persons.1,2 These rankings exist even though prescription opioid dispensing rates have fallen from 102.6 per 100 persons in 2015 to 72.3 per 100 persons in 2019.3 Aligning with this trend, while research shows this problem began with prescription opioids in the late 1990’s, it …


Facilitating Analysis Of Toxoplasma Gondii Bradyzoite Metabolic Activity Via Image Processing And Multivariate Logistic Regression For High Throughput Classification Of Mitochondrial Morphologies, Brooke Place Jan 2021

Facilitating Analysis Of Toxoplasma Gondii Bradyzoite Metabolic Activity Via Image Processing And Multivariate Logistic Regression For High Throughput Classification Of Mitochondrial Morphologies, Brooke Place

Theses and Dissertations--Biomedical Engineering

Approximately a third of the population worldwide is chronically infected by the parasite Toxoplasma gondii. During chronic infection the parasite resides within tissue cysts as the poorly understood bradyzoite form. Observation of these bradyzoites via microscopic imaging within tissue cyst purified from infected mouse brains has shown metabolic activity with heterogeneous replication potential. With fluorescence microscopy imaging targeting the parasite’s actively respiring mitochondria, the parasite’s metabolic state can be further investigated as the morphology of mitochondria can be associated with specific physiologic states. However, manually classifying mitochondrial morphologies from these images can be tedious and prone to error as …


Building Public Health In A Rural State: Strategies For Preventing Disease In Kentucky, 1883-1914, Abigail Stephens Jan 2021

Building Public Health In A Rural State: Strategies For Preventing Disease In Kentucky, 1883-1914, Abigail Stephens

Theses and Dissertations--History

During the period from 1883-1914, the Kentucky State Board of Health developed strategies for preventing disease in the state by enforcing hard power measures of vaccination, quarantine, and isolation of disease suspects, and through the soft power measures of written and spoken communication. Throughout this period their efforts to prevent and contain disease were limited by inadequate funding as well as opposition from the public, local authorities, and the state legislature, demonstrating that while hard power measures can be effective in combating disease, they cannot be fully successful without support from the people they aim to protect.


Application Of Genetic Techniques To Investigate Chlamydia Trachomatis Type Iii Secretion Effector Biology, Gabrielle Keb Jan 2021

Application Of Genetic Techniques To Investigate Chlamydia Trachomatis Type Iii Secretion Effector Biology, Gabrielle Keb

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chlamydia trachomatis is the causative agent of the most reported bacterial sexually transmitted disease in the United States. The establishment of an intracellular niche within mucosal epithelium is sufficient to drive immunopathology and disease sequela. As obligate intracellular bacteria, Chlamydia spp. have evolved numerous mechanisms for establishing an intracellular growth environment. The type III secretion system (T3SS) delivers effector proteins to the host cytosol and is essential for C. trachomatis invasion and development. The effectors TmeA, TmeB, and TarP, are all secreted during C. trachomatis invasion. TarP and TmeA have been associated with manipulation of actin networks and are …


Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates Jan 2021

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …


Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu Jan 2021

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4+ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4+ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …


Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral Jan 2021

Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral

Theses and Dissertations--Pharmacy

Immune checkpoint inhibitors (ICIs), especially those that target programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), have been shown to provide substantial clinical benefit in many patients with non-small cell lung cancer (NSCLC). While these therapeutic agents can be highly effective in the correct context, the biological systems that malignant cells draft from normal activities of the cell are poorly characterized. Tumor cell-specific expression of PD-L1 is likely important for clinical benefit from PD-1 and PD-L1 inhibitors. It is known that PD-L1 is inappropriately expressed in many cancers harboring mutations in the RAS family of genes. …


Delineating The Biosynthesis Of Capuramycin-Type Antibiotics, Ashley L. Biecker Jan 2021

Delineating The Biosynthesis Of Capuramycin-Type Antibiotics, Ashley L. Biecker

Theses and Dissertations--Pharmacy

New antibiotic scaffolds with novel drug targets are needed to combat the rise of drug-resistant, infectious microorganisms. The bacterial translocase I is a ubiquitous enzyme in the peptidoglycan biosynthetic pathway that has yet to be targeted by clinically used antibiotics. It catalyzes the transfer of N-acetylmuramoyl-pentapeptide to undecaprenylphosphate in order to generate lipid I during cell wall biosynthesis. A screening of bacterial translocase I inhibitors led to the discovery of the novel compound capuramycin and its analogues: A-500359s, A-503083s, and A-102395, produced by various species of actinomycetes. The capuramycins show potent activity against the bacterial translocase I with IC50s …


Enhancing Drug Overdose Mortality Surveillance Through Natural Language Processing And Machine Learning, Patrick J. Ward Jan 2021

Enhancing Drug Overdose Mortality Surveillance Through Natural Language Processing And Machine Learning, Patrick J. Ward

Theses and Dissertations--Epidemiology and Biostatistics

Epidemiological surveillance is key to monitoring and assessing the health of populations. Drug overdose surveillance has become an increasingly important part of public health practice as overdose morbidity and mortality has increased due in large part to the opioid crisis. Monitoring drug overdose mortality relies on death certificate data, which has several limitations including timeliness and the coding structure used to identify specific substances that caused death. These limitations stem from the need to analyze the free-text cause-of-death sections of the death certificate that are completed by the medical certifier during death investigation. Other fields, including clinical sciences, have utilized …


Cell And Biofilm Adhesion Strength Quantified By The Laser Spallation Technique Yields A Novel Biocompatibility Metric, The Adhesion Index, James Boyd Jan 2021

Cell And Biofilm Adhesion Strength Quantified By The Laser Spallation Technique Yields A Novel Biocompatibility Metric, The Adhesion Index, James Boyd

Theses and Dissertations--Mechanical and Aerospace Engineering

Implant associated infections are one of the leading causes of hospital acquired infections in the United States. Medical orthopedic implant devices are designed to improve adhesion of relevant cells within our body. In the case of orthopedic implants, osteoblast cells will adhere and allow for proper integration with the body’s bones. However, virulent bacteria will also adhere onto medical implants and proliferate into biofilms. Bacterial biofilms become extremely difficult to eradicate clinically as antibiotics are not as effective, resulting in severe infections or loss of implant. The aim of this research is to quantify the adhesion strength differential between relevant …