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Full-Text Articles in Medicine and Health Sciences

Tissue Kallikrein 1 Cleaves Complement Factor C3 And Activates The Alternative Complement Pathway, Sarah E. Sartain, Andrew Yee, Paula Jacobi Jan 2025

Tissue Kallikrein 1 Cleaves Complement Factor C3 And Activates The Alternative Complement Pathway, Sarah E. Sartain, Andrew Yee, Paula Jacobi

Research Data

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), characterized by microvascular endothelial damage and severe renal injury, negatively affects HSCT survivorship with high mortality and long-term renal morbidity. After HSCT, innate immunity and inflammation are often dysregulated. The alternative complement pathway (AP) of the innate immune system is overactivated in HSCT-TMA, but the mechanisms of its initiation are poorly described. Complement component C3 of the AP can be cleaved by proteases outside of the AP. Because mRNA expression of tissue kallikrein 1 (KLK1), an inflammatory serine protease that produces kinins, has been found to be markedly elevated in the renal endothelium …


Aneurysmal Dilatation Following Common Femoral Artery Directional Atherectomy, Timothy H.H. Kam, Bryan P. Yan, Guangming Tan Jan 2025

Aneurysmal Dilatation Following Common Femoral Artery Directional Atherectomy, Timothy H.H. Kam, Bryan P. Yan, Guangming Tan

Journal of the Hong Kong College of Cardiology

Aneurysmal dilatation is an uncommon but serious complication of directional atherectomy for heavily calcified lower extremity arterial disease. In the absence of established treatment guidelines, this case report describes the successful endovascular management of a common femoral artery aneurysm following directional atherectomy using covered stents.


Effects Of Round-Up On The Environment, Sandra J. Marcu Jan 2025

Effects Of Round-Up On The Environment, Sandra J. Marcu

Journal of Earth and Life Science

Many people around the world have used and still currently use Roundup but are unaware of the effects it has on the environment. Roundup is a spray on application weedkiller that is widely used around the world today both residentially and commercially. It enables its user to grow a garden or a field of crops with a no-tilling approach to eliminate weeds. It is a well-known and popular choice for killing weeds that has been around since the mid 1970’s (Oca, 2017). John Franz, a Monsanto scientist discovered that glyphosate (main ingredient in Roundup) was an herbicide or weedkiller, and …


Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer Jan 2025

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …


Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo Jan 2025

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …


Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta Jan 2025

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …


The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry Jan 2025

The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry

Graduate Theses/Dissertations

HIV-1 is the virus that causes acquired immunodeficiency syndrome (AIDS), and currently, there is no cure once an individual is infected. The development of new drugs targeting HIV-1 replication steps is essential for keeping viral loads low or undetectable to prevent further transmission. An attractive replication step for new drug targets is viral capsid uncoating, where the virus loses the protein structure encapsulating the genome. The exact mechanism of capsid uncoating is unknown; however, several host-factors may be involved including protein SPTBN1. Recent studies have shown a significant decrease in viral infectivity when SPTBN1 is knocked down, yet its role …


Chronic Administration Of A Cannabis-Derived Mixture At An Antihyperalgesic Dose Does Not Significantly Enhance Hepatotoxicity Or The Development Of Metabolic Dysfunction-Associated Steatohepatitis In Male Mice, Kim B. Pedersen, Tomislav Jelesijevic, Tamara M. Morris, Sarah M. Melton, Ashley S. Henderson, John F. Glenn, Gregory J. Davenport, Martin J.J. Ronis, Peter J. Winsauer Jan 2025

Chronic Administration Of A Cannabis-Derived Mixture At An Antihyperalgesic Dose Does Not Significantly Enhance Hepatotoxicity Or The Development Of Metabolic Dysfunction-Associated Steatohepatitis In Male Mice, Kim B. Pedersen, Tomislav Jelesijevic, Tamara M. Morris, Sarah M. Melton, Ashley S. Henderson, John F. Glenn, Gregory J. Davenport, Martin J.J. Ronis, Peter J. Winsauer

School of Medicine Faculty Publications

Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic …


Case Report: Disseminated Herpes Simplex Virus Complicated By Hemophagocytic Lymphohistiocytosis In A Neonate, Nicholas Tadros, Nihal Godiwala Jan 2025

Case Report: Disseminated Herpes Simplex Virus Complicated By Hemophagocytic Lymphohistiocytosis In A Neonate, Nicholas Tadros, Nihal Godiwala

School of Medicine Faculty Publications

Neonatal herpes simplex virus (HSV) infection carries a high mortality rate due to its potential to cause disseminated disease involving multiple organ systems, which can rapidly progress to shock and death if not promptly treated. In rare cases, neonates may mount an uncontrolled inflammatory response leading to hemophagocytic lymphohistiocytosis (HLH), a severe hyperinflammatory syndrome. We present a case of neonatal HSV infection complicated by HLH, highlighting the challenges of managing both conditions concurrently. Our therapeutic approach demonstrated a reduction in systemic inflammation and viral load; however, despite these efforts, the patient developed multiorgan failure and ultimately died from the initial …


Pancreatic Cancer In Appalachia: An Examination Of Detection, Associated Factors, And Provider Experiences With A Focus On West Virginia, Melissa Mae Elder Jan 2025

Pancreatic Cancer In Appalachia: An Examination Of Detection, Associated Factors, And Provider Experiences With A Focus On West Virginia, Melissa Mae Elder

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

Pancreatic Cancer in Appalachia: An Examination of Detection, Associated Factors, and Provider Experiences with a Focus on West Virginia

Melissa M. Elder

Introduction: The Appalachian population accounts for a substantial proportion of the United States and are uniquely susceptible to health care disparities. The Appalachian Regional Commission has reported on the inequities found within the Appalachian region as part of its formal establishment in 1965. When compared to the Non-Appalachian U.S., Appalachia experiences a higher incidence of chronic disease such as diabetes, cancer, lung, and liver disease; mortality from diseases of despair constituting prescription drug, alcohol, illegal drug use, …


One And Half Versus Bi-Ventricular Repair In Pediatric E Bstein Anomaly, Short-Term Outcomes Retrospective Analysis, Rania Abushokka, Hanan Mohammed Hassan, Ahmed Meawad, Ahmed Algebaly Jan 2025

One And Half Versus Bi-Ventricular Repair In Pediatric E Bstein Anomaly, Short-Term Outcomes Retrospective Analysis, Rania Abushokka, Hanan Mohammed Hassan, Ahmed Meawad, Ahmed Algebaly

Journal of Medicine in Scientific Research

-Background: The application of one and half-ventricular repair in Ebstein anomaly(EA) should be considered, in association with effective cone repair, to reduce the volume preload on a dysfunctional right ventricle, and to take the benefit of obtaining ante-grade pulmonary blood flow. The one and half-ventricular repair that applied in patients with hypoplastic sub pulmonic ventricle can alternate effectively the Fontan pathway. This provides pulsatility in pulmonary circulation. However, pressure elevation in superior vena cava (SVC) and right atrial hypertension can occur in patient’s undergone one and half ventricular repair. Aim The aim of this study to evaluate the short-term outcomes …


A Historic Case Of Relapsing-Remitting Alzheimer's Disease In An Adolescent Attributed To Scarlet Fever., Richard Lathe, Brian J. Balin Jan 2025

A Historic Case Of Relapsing-Remitting Alzheimer's Disease In An Adolescent Attributed To Scarlet Fever., Richard Lathe, Brian J. Balin

PCOM Scholarly Works

We draw attention to a historic case of a boy who suffered from scarlet fever (typically caused by the bacterium Streptococcus pyogenes) at age 7 years and went on to develop the symptoms of Alzheimer's disease (AD). His physicians believed that the subsequent dementia was related to the infection. After death at 24 years of age, postmortem brain examination revealed abundant AD-type senile plaques and fibrils, formally confirming AD. Other potential causes of early-onset dementia are discussed, but these are distinct from patient E.H. This case is pertinent regarding the current debate about the potential role of infection in …


Blurry With A Chance Of Ultrasound: A Case Of Sudden Vision Loss, Anjeza Cipi, Emily Sealy Jan 2025

Blurry With A Chance Of Ultrasound: A Case Of Sudden Vision Loss, Anjeza Cipi, Emily Sealy

Department of Emergency Medicine Faculty Publications

[Case presentation] A 30-year-old man with Crohn’s disease presented to the emergency department (ED) with sudden, painless vision loss in his left eye. He described a central dark spot that rapidly progressed over 5 minutes to near-complete central vision loss, sparing peripheral vision. He denied trauma, exertion, Valsalva, or anticoagulant use. Point-of-care ultrasound (POCUS) was performed on supine patient using a high-frequency linear probe (10-15 MHz) with copious gel over the closed eyelid, avoiding direct pressure. While instructing the patient to look in different directions, the eye was scanned in its entirety in transverse and sagittal planes. Gain and depth …


Epidemiology Of Recurrent Herpes Labialis Among Dentistry Students: A Cross-Sectional Survey In Egypt, Sara Abdelwahed, Dalia Ghalwash, Al Hassan Diab Jan 2025

Epidemiology Of Recurrent Herpes Labialis Among Dentistry Students: A Cross-Sectional Survey In Egypt, Sara Abdelwahed, Dalia Ghalwash, Al Hassan Diab

Dentistry

Aim: Recurrent herpes labialis (RHL) is a common viral infection with significant psychosocial and clinical implications. Dental students are particularly vulnerable due to stress and frequent patient contact, yet data on their epidemiology in Egyptian cohorts are scarce. The study aimed to determine the prevalence, recurrence patterns, and associated risk factors of RHL among dentistry students in Egypt. Materials and Methods: A cross-sectional survey was conducted among 559 dentistry students at the British University in Egypt. A structured, self-administered questionnaire captured sociodemographic data, history of RHL episodes, frequency, severity, and triggering factors. Data were analyzed using descriptive statistics and Chi-square …


Rwanda's Natural Remedies: A Fresh Look At The Fight Against Malaria, Leandre Nsabimana Ndisanze Jan 2025

Rwanda's Natural Remedies: A Fresh Look At The Fight Against Malaria, Leandre Nsabimana Ndisanze

Pomona Senior Theses

Malaria remains one of the most devastating parasitic diseases globally, disproportionately affecting sub-Saharan Africa, where Rwanda continues to face high transmission rates and rising resistance to conventional interventions. Despite decades of control efforts, the emergence of drug-resistant Plasmodium falciparum and insecticide-resistant Anopheles mosquitoes threatens to reverse recent gains. This research responds to the urgent need for sustainable and culturally relevant alternatives by exploring the therapeutic potential of Rwandan traditional medicinal plants. These indigenous remedies, long used by local healers, offer an underexplored reservoir of bioactive compounds that may provide the basis for novel antimalarial drugs.

The central hypothesis of this …


Traditional And Non-Traditional Behavioral Tests Demonstrate The Attenuation Of Cognitive Deficits By Therapeutic Hypothermia In A Rat Model Of Neonatal Hypoxic-Ischemic Encephalopathy, Angela Saadat, Cortney Kaszowski, Haree Pallera, Frank Lattanzio, Richard A. Britten, Asna Sulaiman, Stephanie Newman, Alireza Hosseini, Tushar Shah Jan 2025

Traditional And Non-Traditional Behavioral Tests Demonstrate The Attenuation Of Cognitive Deficits By Therapeutic Hypothermia In A Rat Model Of Neonatal Hypoxic-Ischemic Encephalopathy, Angela Saadat, Cortney Kaszowski, Haree Pallera, Frank Lattanzio, Richard A. Britten, Asna Sulaiman, Stephanie Newman, Alireza Hosseini, Tushar Shah

Department of Pediatrics Faculty Publications

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) is neurological disease caused by the deprivation of oxygen and blood flow to the brain during the developmentally-critical perinatal period. Therapeutic hypothermia (TH) is the standard of care treatment for HIE, though cognitive deficits can persistent throughout life despite treatment. The nature of these deficits, and the impacts of TH and sex are not well understood, and this presents a key barrier in the development of novel therapeutics.

Methods: The goal of this study was to enhance the characterization and measurement of cognitive outcomes with tasks that measure spontaneous behaviors in a rodent models of …


Assessment Of Primary Malignancy Risk Following Initiation Of Biologic Therapy In Psoriasis Patients, Chunghwan Ro, Ana Ormaza Vera, Waleed Adawi, Alexander Yap, Clinton W. Enos Jan 2025

Assessment Of Primary Malignancy Risk Following Initiation Of Biologic Therapy In Psoriasis Patients, Chunghwan Ro, Ana Ormaza Vera, Waleed Adawi, Alexander Yap, Clinton W. Enos

Department Dermatology Faculty Publications

Limited evidence exists regarding the long-term oncologic safety of biologic therapies, particularly interleukin (IL)-17 inhibitors (IL-17i) and IL-23i, in the management of psoriasis. This propensity-score-matched retrospective-cohort study assessed the risk of developing a primary malignancy within 10-years following exposure to an FDA-approved biologic among psoriasis patients compared to biologic-naïve controls. After propensity-score-matching, 32,230 biologic-exposed patients were further grouped into cohorts of tumor necrosis factor inhibitors (TNFi, n=16,011), IL-23i (n=5,604), IL-12/23i (n=3,856), and IL-17i (n=5,467). During a 10-year period, TNFi-treated patients had a reduced risk of developing any primary malignancy compared to biologic-naïve psoriasis patients [HR 0.80(0.73-0.87)]. Similarly, a lower incidence …


Surgical Management Of Gastroenteropancreatic Neuroendocrine Tumors, Lisa M. Kenney, Marybeth Hughes Jan 2025

Surgical Management Of Gastroenteropancreatic Neuroendocrine Tumors, Lisa M. Kenney, Marybeth Hughes

Department Surgery Faculty Publications

Background/Objectives: Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. Methods: A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. Results: For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored …


The Impact Of Ultra-Processed Foods On Cardiovascular Diseases And Cancer: Epidemiological And Mechanistic Insights, Olorunfemi Oyewole Babalola, Ebenezer Akinnusi, Paul Olamide Ottu, Kpomah Bridget, Godspower Oyubu, Samuel Ayomikun Ajiboye, Sakariyau Adio Waheed, Amafili Chibuzo Collette, Hameedah Oluwatoyin Adebimpe, Chibuzo Valentine Nwokafor, Ebenezer Ayomide Oni, Precious Olayinka Aturamu, Opeyemi Iwaloye Jan 2025

The Impact Of Ultra-Processed Foods On Cardiovascular Diseases And Cancer: Epidemiological And Mechanistic Insights, Olorunfemi Oyewole Babalola, Ebenezer Akinnusi, Paul Olamide Ottu, Kpomah Bridget, Godspower Oyubu, Samuel Ayomikun Ajiboye, Sakariyau Adio Waheed, Amafili Chibuzo Collette, Hameedah Oluwatoyin Adebimpe, Chibuzo Valentine Nwokafor, Ebenezer Ayomide Oni, Precious Olayinka Aturamu, Opeyemi Iwaloye

Chemistry & Biochemistry Faculty Publications

Ultra-processed foods (UPFs) are increasingly recognized as contributors to the pathogenesis of cardiovascular diseases (CVDs) and cancer due to their adverse compositional and mechanistic effects. UPFs, distinguished by their high content of unhealthy fats, sodium, refined sugars, and synthetic additives, significantly increase dyslipidemia, hypertension, and obesity, which are key risk factors for CVDs. Chronic consumption leads to systemic inflammation, gut microbiota dysbiosis, endothelial dysfunction, and oxidative stress. Additives such as artificial sweeteners and sodium nitrites in UPFs are associated with carcinogenesis through mechanisms involving genotoxicity and promotion of inflammatory microenvironments. This review critically evaluates existing epidemiological, mechanistic, and clinical evidence …


An E. Coli Two-Hybrid System To Investigate Human Protein-Protein Interactions, Rebecca M. Richardson, Sarah M. Ho, Lane Tong, Morgan G. Daniels, Steven M. Pascal Jan 2025

An E. Coli Two-Hybrid System To Investigate Human Protein-Protein Interactions, Rebecca M. Richardson, Sarah M. Ho, Lane Tong, Morgan G. Daniels, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Abstract

The LexA-E. coli two-hybrid (LexA-E2H) system was initially developed to study interactions between microbial proteins in an Escherichia coli (E. coli) environment. We here demonstrate its utility for studying mammalian protein interactions. Specifically, this study uses LexA-E2H to provide the first direct and quantitative validation of Glucose Regulated Protein 78 (GRP78) binding to the cleaved-Prostate Apoptosis Response 4 (cl-Par-4) tumor suppressor. Furthermore, the results establish that this interaction does not require phosphorylation of either protein. MacConkey agar was used for initial detection of the interaction through colorimetric colony screening, distinguishing pale white-pink colonies (+ interaction) from …


Emerging Nanotechnology Approaches For Blood Disorders: A Comprehensive Review Of Nano-Hematinics And Plant-Based Nanomedicines, Hassan Abdulsalam Adewuyi, Khairat Shamsudeen, Fatima Mahmoud Muhammad, Adeola Kolawole Victor, Sakariyau Adio Waheed, Adepeju Matilda Adekoya, Kashim Ibrahim Muhammad, Blessing Temitayo Longe, Abdulgaffar Abdulquddus Jan 2025

Emerging Nanotechnology Approaches For Blood Disorders: A Comprehensive Review Of Nano-Hematinics And Plant-Based Nanomedicines, Hassan Abdulsalam Adewuyi, Khairat Shamsudeen, Fatima Mahmoud Muhammad, Adeola Kolawole Victor, Sakariyau Adio Waheed, Adepeju Matilda Adekoya, Kashim Ibrahim Muhammad, Blessing Temitayo Longe, Abdulgaffar Abdulquddus

Chemistry & Biochemistry Faculty Publications

Background: Disorders affecting blood components, such as anemia, coagulopathies, and hematologic malignancies, continue to pose significant global health burdens. Traditional therapies often fall short due to adverse effects, limited bioavailability, and insufficient targeting of disease sites.

Objective: This review synthesizes current advances in nano-hematinics and plant-based nanomedicines (phyto-nanomedicines) as innovative strategies for managing blood-related conditions. These nanoscale interventions are designed to enhance therapeutic precision, bioactivity, and safety.

Methods: A systematic review was conducted using major scientific databases including PubMed, Scopus, Web of Science, and ScienceDirect. Search terms were carefully selected to retrieve literature published between 2015 and 2024 that discussed …


Structural And Interpersonal Determinants Of Covid-19 Vaccine Uptake In Vulnerable Populations Of The United States, Alyea Wood Jan 2025

Structural And Interpersonal Determinants Of Covid-19 Vaccine Uptake In Vulnerable Populations Of The United States, Alyea Wood

Capstone Showcase

Since its introduction in late 2020, the uptake of the COVID-19 vaccine has had the lowest rates in marginalized populations like minorities, elderly, and those of low socioeconomic status. Decreased rates of vaccination uptake in these groups has resulted in increased burden of disease and subsequently higher rates of hospitalization and death. Many inequities in poor COVID-19 health outcomes can be explained by examining common predictive factors that determine vaccination rates in these United States populations. This special article research aims to explore these various predictive factors with the goal to provide targeted strategies to boost COVID-19 vaccination rates, especially …


Caspases Protect Against Hyperglycemia Induced Necroptosis-Like Cell Death In Brain Endothelial Cells, Aleena S. Mathew Jan 2025

Caspases Protect Against Hyperglycemia Induced Necroptosis-Like Cell Death In Brain Endothelial Cells, Aleena S. Mathew

Theses and Dissertations

Acute diabetes characterized by high spikes in blood glucose levels in association with severe hyperglycemia can lead to an increased risk of ischemic stroke in the brain. To better understand high blood glucose levels, hyperglycemia, in the brain we explored its effects on endothelial cells. Endothelial cells line the inner walls of blood vessels and are directly impacted in hyperglycemia. Brain endothelial cells are a major component of the blood brain barrier (BBB) which tightly regulates the brain’s microenvironment. The type of cell death such as apoptosis, caspase dependent, or necroptosis, caspase independent, can exacerbate diabetes associated complications. There is …


Gain-Of-Function Tp53 Mutations Induce Non-Canonical Nf-Κb Transcriptional Targets To Promote Tumor Development, Kelsey A. Yutan Jan 2025

Gain-Of-Function Tp53 Mutations Induce Non-Canonical Nf-Κb Transcriptional Targets To Promote Tumor Development, Kelsey A. Yutan

Scripps Senior Theses

Background: Gain-of-function TP53 mutations have previously been shown to induce chromosomal instability (CIN) in cancer cells, triggering the cGAS-STING innate immune response and subsequently activating the non-canonical NF-κB (NC-NF-κB) signaling pathway. This signaling cascade promotes cancer cell metastasis and an immunosuppressive tumor microenvironment (TME), significantly impacting tumor development and progression. However, the precise downstream mechanisms by which the mutp53-CIN-cGAS-STING-NC-NF-κB signaling pathway facilitates tumor development and progression remain poorly understood. Here, our objective was to identify direct downstream targets of mutp53-CIN-cGAS-STING-induced NC-NF-κB signaling that potentially impact the TME to promote the development and progression of oral squamous cell carcinoma.

Methods …


Exploring Psychological Implications Of The Contemporary Lung Transplant, Isaac C. Machar Jan 2025

Exploring Psychological Implications Of The Contemporary Lung Transplant, Isaac C. Machar

Williams Honors College, Honors Research Projects

Since its inception in 1963 at the University of Mississippi Medical Center, more than 50,000 lung transplant procedures have been performed. During its 50-year anniversary, 2023 saw just over 3,000 lung transplants performed in the United Sates. However, as this procedure continues to increase in execution each year, it is critical that the psychological implications of this procedure are explored. In this paper, I hope to develop an understanding of the psychological background of contemporary lung transplantation. Reviewing the lung and double lung transplant, the goal is to apply biopsychology principles to the field. Background information about transplant science is …


Astrocyte Specific Enhancers In The Cortex And Striatum Of Mice, Mikaela Kottelich Jan 2025

Astrocyte Specific Enhancers In The Cortex And Striatum Of Mice, Mikaela Kottelich

Williams Honors College, Honors Research Projects

Among glial cells, astrocytes have a prevalent influence on supporting neuronal function and overall brain health. Specifically targeting this cell type for disease treatment is an existing issue. Other cell types tend to express the desired treatment, which is not always wanted and can lead to unintended, negative consequences. Astrocytes contribute largely to maintaining the blood brain barrier, which is disrupted in Parkinson’s disease. Certain genes are thought to be the reason for this disruption, so if they can be specifically targeted in astrocytes with a specific enhancer, the disruption of the disease could be reversed. In our experiment, we …


Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit Jan 2025

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …


Skinrisk Ai, Spencer Simms Jan 2025

Skinrisk Ai, Spencer Simms

Williams Honors College, Honors Research Projects

SkinRisk AI is an exploration of the opportunities for implementing machine learning (ML) and artificial intelligence (AI) in the medical technology field, specifically in the early detection of skin cancer. This project presents the design, development, and evaluation of a mobile application that allows users to capture images of skin lesions and receive a machine learning assisted risk assessment. The system combines a convolutional neural network (CNN) for image analysis with an intuitive mobile app built using Flutter, FastAPI, and Supabase to deliver real time screening.

Motivated by the rising skin cancer rates and importance of early detection, SkinRisk AI …


Critical Analysis Of Gestational Diabetes Risk Factors: A Systematic Review, Madison Keich, Madeleine Ray, Mia Ross Jan 2025

Critical Analysis Of Gestational Diabetes Risk Factors: A Systematic Review, Madison Keich, Madeleine Ray, Mia Ross

Williams Honors College, Honors Research Projects

Gestational Diabetes Mellitus (GDM) is a common complication of pregnancy that causes an increased blood sugar that can affect both the mother's and baby’s health. A variety of factors can increase the risk of developing the disease, including race, socioeconomic status, and prenatal education. Each of these factors contributes to the experience of one’s maternal care. Expecting mothers may not understand how significant GDM is, and its potential to result in negative outcomes. It is important to review these factors, acknowledge them, and help reduce health disparities caused by them. Nurses are vital to assessing and delivering patient education on …


The Quality-Of-Life Benefits And Risk Of Isotretinoin (Accutane) In Acne Treatment: A Systematic Review, Noelia Valencia Zuniga Jan 2025

The Quality-Of-Life Benefits And Risk Of Isotretinoin (Accutane) In Acne Treatment: A Systematic Review, Noelia Valencia Zuniga

Honors Undergraduate Theses

Acne vulgaris is a prevalent dermatological condition, particularly affecting adolescents and young adults. While often treated as a cosmetic issue, acne can significantly impair a patient's mental health and overall quality of life (QoL). Isotretinoin, commonly known as Accutane, is widely regarded as the most effective treatment for severe and persistent acne. However, its use is controversial due to a range of potential side effects, including psychiatric symptoms, teratogenicity, and other systemic complications. To better understand the risk-benefit profile of isotretinoin in acne treatment, we conducted a systematic review, focusing on the QoL benefits and risks associated with its use. …