Diseases Commons^™

Prednisolone For Copd Exacerbations: Time For A Rethink, Sanjay Ramakrishnan

Research outputs 2022 to 2026

Prednisolone given universally for COPD exacerbations causes harm without any benefit. Patients deserve blood eosinophil-guided prednisolone treatment for COPD exacerbations.

Prognostic And Predictive Value Of Metformin In The European Organisation For Research And Treatment Of Cancer 1325/Keynote-054 Phase Iii Trial Of Pembrolizumab Versus Placebo In Resected High-Risk Stage Iii Melanoma, Oliver J. Kennedy, Michal Kicinski, Sara Valpione, Sara Gandini, Stefan Suciu, Christian U. Blank, Georgina V. Long, Victoria G. Atkinson, Stéphane Dalle, Andrew M. Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Marye Boers-Sonderen, Anna M. Di Giacomo, Alfonsus J. M. Van Der Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Alexander C. J. Van Akkooi, Caroline Robert, Alexander M. M. Eggermont, Paul Lorigan, Mario Mandala

Research outputs 2022 to 2026

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial. Methods: Patients with resected high-risk stage IIIA, IIIB, or IIIC melanoma received 200 mg of pembrolizumab (n = 514) or placebo (n = 505) every 3 weeks for twelve months. Pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) at approximately 42 months …

Association Between Immunoglobulin G N-Glycosylation And Lupus Nephritis In Female Patients With Systemic Lupus Erythematosus: A Case-Control Study, Xinxia Lu, Liangao Wang, Meng Wang, Yuejin Li, Qinqin Zhao, Yanjun Shi, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography …

Covid-19 In Western Australia: ‘The Last Straw’ And Hopes For A ‘New Normal’ For Parents Of Children With Long-Term Conditions, Stephanie Smith, Mary Tallon, James Smith, Lauren Jones, Evalotte Mörelius

Research outputs 2022 to 2026

Background: Children with long-term conditions are vulnerable due to the treatments required for their conditions. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, Western Australians experienced restrictions that changed daily life activities but were able to return to some of their previous routines due to the restrictions. Aim: The study explored the stress experiences of parents caring for children with long-term conditions during COVID-19 in Western Australia. Design and Participants: The study was codesigned with a parent representative caring for children with long-term conditions to ensure essential questions were targeted. Twelve parents of children with various long-term conditions …

How General Practitioners And Patients Discuss Type 2 Diabetes Mellitus And Cardiovascular Diseases Concerns During Consultations: Implications For Digital Health, Urvashi Rohilla, Jayashanthi P. Ramarao, Jared Lane, Neha N. Khatri, James Smith, Kathleen Yin, Annie Y. S. Lau

Research outputs 2022 to 2026

Objective: To analyse general practitioner–patient consultations about type 2 diabetes mellitus or cardiovascular diseases and describe (i) the nature of self-management discussions; (ii) actions required from patients during and after consultation regarding self-management; and (iii) implications for digital health to support patients during (and after) consultation. Method: This study screened 281 general practitioner consultations conducted in 2017 within the UK general practice setting from an existing dataset containing videos and transcripts of consultations between GPs and patients. Secondary analysis was conducted using a multi-method approach, including descriptive, content, and visualisation analysis, to inform the nature of self-management discussions, what actions …

It's Quite Good Fun: A Qualitative Study Of A Singing/Songwriting Programme For People With Parkinson's Disease And Their Spouses, Deborah Hersh, Shi J. Kong, Jessica Smith

Research outputs 2022 to 2026

Background: : Group singing for people with Parkinson's disease (PD) is an established intervention not only to improve voice and speech difficulties but also for emotional and social benefit. Less is known about the experiences of group singing on the couple—the person with PD and their spouse or partner together—and studies have not specifically tracked impact through time or in combination with songwriting. Aims: : To understand the impact of group singing/songwriting on couples (participants with PD and their spouses) to unpack whether this broader view might help explain why such interventions are reported as beneficial. Using a trajectory approach, …

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A. Schultz, Zahra Shirzadi, Aaron P. Schultz, Lei Liu, Colleen D. Fitzpatrick, Eric Mcdade, Nicolas R. Barthelemy, Alan Renton, Bianca Esposito, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D. Chen, Alison Goate, Ricardo F. Allegri, Tammie L. S. Benzinger, Sarah Berman, Helena C. Chui, Anne M. Fagan, Martin R. Farlow, Nick C. Fox, Brian A. Gordon, Gregory S. Day, Neill R. Graff-Radford, Jason J. Hassenstab, Bernard J. Hanseeuw, Anna Hofmann, Clifford R. Jack Jr, Mathias Jucker, Celeste M. Karch, Robert A. Koeppe, Jae-Hong Lee, Allan I. Levey, Johannes Levin, Ralph Martins, Hiroshi Mori, John C. Morris, James Noble, Richard J. Perrin, Pedro Rosa-Neto, Stephen P. Salloway, Raquel Sanchez-Valle, Peter R. Schofield, Chengjie Xiong, Keith A. Johnson, Randall J. Bateman, Reisa A. Sperling, Jasmeer P. Chhatwal, Dominantly Inherited Alzheimer Network Investigators

Research outputs 2022 to 2026

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Two-Year Prognostic Utility Of Plasma P217+Tau Across The Alzheimer’S Continuum, A. Feizpour, V. Doré, J. D. Doecke, Z. S. Saad, G. Triana-Baltzer, R. Slemmon, P. Maruff, N. Krishnadas, P. Bourgeat, K. Huang, C. Fowler, S. R. Rainey-Smith, A. I. Bush, L. Ward, J. Robertson, R. N. Martins, C. L. Masters, V. L. Villemagne, J. Fripp, H. C. Kolb, C. C. Rowe

Research outputs 2022 to 2026

Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid- (A ) and tau in Alzheimer’s Disease (AD). However, its association with longitudinal cognition and comparative performance to PET A and tau in predicting cognitive decline are unknown. Objectives: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on A (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost …

Externalizing Traits: Shared Causalities For Covid-19 And Alzheimer's Dementia Using Mendelian Randomization Analysis, Haotian Wang, Mingyang Cao, Yingjun Xi, Weijie Cao, Xiaoyu Zhang, Xiaoni Meng, Deqiang Zheng, Lijuan Wu, Wei Wang, Di Liu, Youxin Wang

Research outputs 2022 to 2026

Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD); however, whether these associations are causal remains unknown. We used the two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse variance–weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio …

Machine-Learning Assessed Abdominal Aortic Calcification Is Associated With Long-Term Fall And Fracture Risk In Community-Dwelling Older Australian Women, Jack Dalla Via, Abadi Gebre, Cassandra Smith, Zulqarnain Gilani, David Suter, Naeha Sharif, Pawel Szulc, John T. Schousboe, Douglas P. Kiel, Kun Zhu, William D. Leslie, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Abdominal aortic calcification (AAC), a recognized measure of advanced vascular disease, is associated with higher cardiovascular risk and poorer long-term prognosis. AAC can be assessed on dual-energy X-ray absorptiometry (DXA)-derived lateral spine images used for vertebral fracture assessment at the time of bone density screening using a validated 24-point scoring method (AAC-24). Previous studies have identified robust associations between AAC-24 score, incident falls, and fractures. However, a major limitation of manual AAC assessment is that it requires a trained expert. Hence, we have developed an automated machine-learning algorithm for assessing AAC-24 scores (ML-AAC24). In this prospective study, we evaluated the …

Genetic And Immunological Insights Into Covid-19 With Acute Myocardial Infarction: Integrated Analysis Of Mendelian Randomization, Transcriptomics, And Clinical Samples, Zequn Zheng, Yueran Zhou, Yongfei Song, Pengxiang Ying, Xuerui Tan

Research outputs 2022 to 2026

Background: Globally, most deaths result from cardiovascular diseases, particularly ischemic heart disease. COVID-19 affects the heart, worsening existing heart conditions and causing myocardial injury. The mechanistic link between COVID-19 and acute myocardial infarction (AMI) is still being investigated to elucidate the underlying molecular perspectives. Methods: Genetic risk assessment was conducted using two-sample Mendelian randomization (TSMR) to determine the causality between COVID-19 and AMI. Weighted gene co-expression network analysis (WGCNA) and machine learning were used to discover and validate shared hub genes for the two diseases using bulk RNA sequencing (RNA-seq) datasets. Additionally, gene set enrichment analysis (GSEA) and single-cell RNA-seq …

Impaired Muscle Function, Including Its Decline, Is Related To Greater Long-Term Late-Life Dementia Risk In Older Women, Simone Radavelli-Bagatini, Helen Macpherson, David Scott, Robin M. Daly, Jonathan M. Hodgson, Simon M. Laws, Kun Zhu, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Background: Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80 years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5 years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ4 (APOE ℇ4) genotype. Methods: Grip strength and TUG were assessed in community-dwelling older women (mean ± SD; age 75.0 ± 2.6 years) at baseline (n = 1225) and 5 years (n = …

Patient Navigation Across The Cancer Care Continuum: An Overview Of Systematic Reviews And Emerging Literature, Raymond J. Chan, Vivienne E. Milch, Fiona Crawford-Williams, Oluwaseyifunmi A. Agbejule, Ria Joseph, Jolyn Johal, Narayanee Dick, Matthew P. Wallen, Julie Ratcliffe, Anupriya Agarwal, Larissa Nekhlyudov, Matthew Tieu, Manaf Al-Momani, Scott Turnbull, Rahul Sathiaraj, Dorothy Keefe, Nicolas H. Hart

Research outputs 2022 to 2026

Patient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, …

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 …

Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix

Honors College Theses

Polycyclic aromatic hydrocarbons are organic compounds that are created synthetically or found in partially burned oil, gasoline, and coal. 2-aminoanthracene (2AA) is a common example of a PAH and can affect lipid and carbohydrate metabolism and resulting in inflammatory problems and oxidative stress. The objective of the research project is to investigate oxidative stress in relation to diabetes in rats exposed to 2AA in utero and a high fat diet later in life. Pregnant dams were separated into treatment groups based on their dosages of 2AA; 0 mg/kg (control), 50 mg/kg (low), 100 mg/kg (high). During the gestation -postpartum period, …

Teaching Assistant Responses To Covid-19: Investigating Relationships Between Stress, Self-Efficacy, And Approaches To Teaching, Cody R. Smith, Deepika Menon, Annette Wierzbicki, Jenny Dauer

Department of Teaching, Learning, and Teacher Education: Faculty Publications

This study investigates the self-efficacy of undergraduate and graduate TAs associated with changes in instruction after the COVID-19 disruption to the spring 2020 semester.

Guiding research questions include: (i) What are the relationships among TA teacher efficacy and stress resulting from the COVID-19 disruption? (ii) What experiences do TAs describe that contribute to their stress and teacher efficacy?

Implications of the results for supporting TAs during similarly stressful events and circumstances are discussed.

Modeling The Spread Of Covid-19 In Spatio-Temporal Context, S.H. Sathish Indika, Norou Diawara, Hueiwang Anna Jeng, Bridget D. Giles, Dilini S.K. Gamage

Mathematics & Statistics Faculty Publications

This study aims to use data provided by the Virginia Department of Public Health to illustrate the changes in trends of the total cases in COVID-19 since they were first recorded in the state. Each of the 93 counties in the state has its COVID-19 dashboard to help inform decision makers and the public of spatial and temporal counts of total cases. Our analysis shows the differences in the relative spread between the counties and compares the evolution in time using Bayesian conditional autoregressive framework. The models are built under the Markov Chain Monte Carlo method and Moran spatial correlations. …

Huntington’S Disease: A Systematic Review And Overview Of Treatments, Madison Mintz

Undergraduate Honors Theses

Huntington’s Disease (HD) is a genetic neurodegenerative disease that is the result of a mutation of the huntingtin gene. The gene is passed in an autosomal dominant fashion and is the result of multiple Cystine, Adenine, and Guanine base repeats. HD symptoms manifest as motor, cognitive, and psychological symptoms that can range of chorea movements to depression or apathy. The disease progresses through various prodromal and clinical stages as the disease starts to manifest. The current technique to diagnose HD is the use of direct genetic testing, which counts the number of repeats. Due to the nature of HD, both …

A Systematic Review To Study The Global Patterns And Policies Of Hiv Harm Reduction Programs And Their Impact Among People Who Inject Drugs, Noura Shaltout, Rania Soliman, Lamia Refaey, Rim Ghazal, Mirna Atteya, Nahla Elmedany

Papers, Posters, and Presentations

Aim: This study aims to provide an updated estimate of HIV prevalence among people who inject drugs (PWID) globally, as well as investigate different policies and methods for applying harm reduction. This article focuses on the two major and the most frequently used harm reduction techniques, Syringe-Service Programs (SSPs) and Opioid Agonist Therapy (OAT). Methods: A comprehensive systematic review was undertaken across multiple international databases during the period of (August-December 2021). For studies conducted before 2005, we used data from a previous published systematic review. Thirty-six studies were included, including studies that had performed HIV testing and had a confirmed …

Acute Myocardial Infarction Among People Living With Hiv: Comparing Immunological And Virological Control By Hispanic Ethnicity Of The All Of Us Research Program Participants, Eugenio Reina

Honors Undergraduate Theses

In the United States, individuals of Hispanic ethnicity receive disproportionately lower-quality healthcare. These healthcare disparities exacerbate unequal access to quality healthcare services, including disparities in cardiovascular disease (CVD) and human immunodeficiency virus (HIV) care. Research on the role of ethnicity on the CVD outcomes of people living with HIV (PLWH) has been limited. We hypothesize that immunological (CD4+ cell count) and virological (HIV viral load) control may play a role in the development of acute myocardial infarction (AMI) among PLWH, and that Hispanic ethnicity may worsen these outcomes.

To verify our hypotheses, we conducted a retrospective cross-sectional study to investigate …

Role Of Endoplasmic Reticulum Stress Response In Parainfluenza Virus Acute To Persistent Infections, Lauren L. Abbitt

Honors Undergraduate Theses

Persistent viral infections are a major health concern, with persistently infected (PI) cells being a source of continued shedding of virus and generation of viral mutants. Here, we hypothesized that cells persistently infected with the enveloped virus parainfluenza virus 5 (PIV5) would show altered expression of endoplasmic reticulum (ER) stress proteins and increased resistance to death caused by drug-induced ER stress. To test this, lysates of mock-infected, PIV5 acute-infected, and PIV5 PI human lung A549 cells were collected and levels of ER stress proteins were compared. Western blotting revealed that immunoglobulin heavy chain binding protein (BiP/GRP78) was present in higher …

The Effect Of L-Citrulline Supplementation On Blood Pressure: An Updated Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Vraj Amin

Honors Undergraduate Theses

Cardiovascular disease remains one of the most prevalent diseases in the United States and has remained as the leading cause of death. Large Mendelian randomization studies have found significant correlations between high blood pressure and cardiovascular disease (CVD). In fact, high blood pressure is the single most important independent risk factor for CVD. The purpose of this study was to determine the effect of L-citrulline on blood pressure to determine whether it could be advised as an effective treatment for high blood pressure. L-citrulline is a naturally occurring amino acid that readily converts to L-arginine within the human body. L-arginine …

Trends In Antibiotic Susceptibility Of Staphylococcus Aureus Isolates In A Pediatric Hospital: An Analysis Of The Impact Of The Sars-Cov-2 Pandemic, Juan Miguel S. Gonzalez Rivero

Honors Undergraduate Theses

Infections caused by the organism Staphylococcus aureus are one of the most common causes for community-associated and healthcare-acquired infections (HAI). Isolates of this bacterium found within the healthcare setting often demonstrate a higher prevalence of antibiotic resistance making these infections difficult to treat. Historically, considerable focus has been placed on methicillin-resistant S. aureus (MRSA), which are strains resistant to β-lactam antibiotics like penicillin, oxacillin and cephalosporins; however, methicillin-sensitive (MSSA) strains may also possess resistance to several first-line antibiotics. Resistance to antibiotics can be acquired through horizontal gene transfer (HGT) by means of mobile genetic elements or by random DNA mutations …

Using Data And Evidence To Improve Quality Of Life For Patients With Alzheimer’S Disease, Ying Wang

2023

As an irreversible, progressive brain disorder, Alzheimer’s disease (AD) imposes a severe burden upon patients and their caregivers, as well as the healthcare system. Of the ten leading causes of death in the United States, Alzheimer’s disease is the only one without a pharmacological intervention that has been proven to cure or delay the onset of the disease. Aging is the primary risk factor contributing to Alzheimer’s disease in the elderly. With an aging population that continues to grow, the challenges for the healthcare system surrounding AD become more and more serious. My dissertation aims to contribute to a better …

Investigation Of Lower Extremity Neuromuscular Function In Individuals With And Without Diabetes, Roya Hoveizavi

Theses and Dissertations--Kinesiology and Health Promotion

Background: Diabetes mellitus is associated with notable neuromuscular and motor dysfunctions that could lead to an increased risk of plantar ulcers and amputations. Several contributing factors, including increased muscle-tendon stiffness and abnormal muscle activation pattern may influence the kinematics and kinetics of walking in people with diabetes and promote formation of plantar ulcers. Hyperglycemia and the resultant accelerated rate of glycation have been recognized as the leading cause of muscle and tendon degeneration, yet the precise mechanisms by which diabetes affects the biomechanical properties of the muscle-tendon unit remains unclear. Altered muscle activity during gait is observed in people with …

An Epidemiological And Pharmacokinetic-Pharmacodynamic Investigation Into The Impact Of Carbapenem-Resistant Enterobacterales, Justin Clark

Theses and Dissertations--Pharmacy

Background: According to the 2019 CDC Antibiotic Resistance Threats Report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, leading to more than 35,000 deaths. Among the most urgent threats identified by the CDC are carbapenem-resistant Enterobacterales (CRE). Despite efforts to control the spread of these organisms, the number of estimated cases between 2012 and 2017 remained stable. In 2017, an estimated 13,100 hospitalized cases of CRE led to approximately 1,100 deaths and $130 million attributable healthcare costs. This dissertation seeks to address this issue from both a pharmacokinetic/pharmacodynamic and epidemiological perspective.

Methods: We evaluated the …

Potential Alzheimer's Disease Plasma Biomarkers, Taylor Estepp

Theses and Dissertations--Epidemiology and Biostatistics

In this series of studies, we examined the potential of a variety of blood-based plasma biomarkers for the identification of Alzheimer's disease (AD) progression and cognitive decline. With the end goal of studying these biomarkers via mixture modeling, we began with a literature review of the methodology. An examination of the biomarkers with demographics and other health factors found evidence of minimal risk of confounding along the causal pathway from biomarkers to cognitive performance. Further study examined the usefulness of linear combinations of biomarkers, achieved via partial least squares (PLS) analysis, as predictors of various cognitive assessment scores and clinical …

The Role Of High Mobility Group Box-1 Pathobiology In Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Shayan Mohammadmoradi

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs) are permanent luminal dilations of the vessel wall that can result in rupture and death. There is currently no evidence-based treatment to prevent or attenuate the development of this devastating condition. Although vascular inflammation is known to be one of the hallmarks of AAA, underlying mechanisms that initiate inflammatory pathways in the aorta are not clearly known. High-mobility group box 1 (HMGB1), a highly conserved nonhistone DNA-binding nuclear protein, may contribute to vascular diseases. Since whole-body genetic deletion of HMGB1 is embryonic lethal, pharmacological approaches have been used to manipulate HMGB1 in mice. However, it remains …

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …