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Articles 3901 - 3930 of 5215

Full-Text Articles in Diseases

Impact Of Covid-19 On Pediatric Gastroenterology Fellow Training In North America, Daniel Mallon, John F Pohl, Uma P Phatak, Melissa Fernandes, John M Rosen, Sarah S Lusman, Cade M Nylund, Candi S Jump, Aliza B Solomon, Arvind Srinath, Andrew Singer, Rula Harb, Norberto Rodriguez-Baez, Kristin L Whitfield Van Buren, Shifra Koyfman, Riha Bhatt, Dellys M Soler-Rodriguez, Mamata Sivagnanam, Christine K Lee, Naspghan Training Committee Covid-19 Survey Working Group Jul 2020

Impact Of Covid-19 On Pediatric Gastroenterology Fellow Training In North America, Daniel Mallon, John F Pohl, Uma P Phatak, Melissa Fernandes, John M Rosen, Sarah S Lusman, Cade M Nylund, Candi S Jump, Aliza B Solomon, Arvind Srinath, Andrew Singer, Rula Harb, Norberto Rodriguez-Baez, Kristin L Whitfield Van Buren, Shifra Koyfman, Riha Bhatt, Dellys M Soler-Rodriguez, Mamata Sivagnanam, Christine K Lee, Naspghan Training Committee Covid-19 Survey Working Group

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training.

METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics.

RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to …


Glycemic Control And Infections Among Us Hemodialysis Patients With Diabetes Mellitus, Jinnie J Rhee, Yuanchao Zheng, Sai Liu, Maria E Montez-Rath, Richard J Hamill, Julie H Ishida, Wolfgang C Winkelmayer Jul 2020

Glycemic Control And Infections Among Us Hemodialysis Patients With Diabetes Mellitus, Jinnie J Rhee, Yuanchao Zheng, Sai Liu, Maria E Montez-Rath, Richard J Hamill, Julie H Ishida, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

INTRODUCTION: Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections.

METHODS: We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived >90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into

RESULTS: In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates …


Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen Jul 2020

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …


Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra Jul 2020

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …


Renal Trajectory Patterns Are Associated With Postdischarge Mortality In Patients With Cirrhosis And Acute Kidney Injury, Ayse L Mindikoglu, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Thomas Taylor, Abbas Rana, Fasiha Kanwal Jul 2020

Renal Trajectory Patterns Are Associated With Postdischarge Mortality In Patients With Cirrhosis And Acute Kidney Injury, Ayse L Mindikoglu, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Thomas Taylor, Abbas Rana, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Little is known about long-term outcomes of acute kidney injury (AKI) in patients with cirrhosis. Outcomes can vary with stage of AKI, chronic kidney disease, and trajectory of renal function.

METHODS: We collected data from the Department of Veterans Affairs and identified 6917 patients with cirrhosis who developed AKI during hospitalization at any of its 127 hospitals, from 2004 through 2014. We used latent class analysis of serial creatinine measurements during the index hospitalization to determine trajectories of renal function.

RESULTS: Overall, 32% of patients died within 90 days of discharge from the hospital and 48% of …


Dynamic Ultrasound Uniquely Reveals Anterior Capsular Tear Communicating With Vastus Intermedius Fibers, Shiv J Patel, Jasvinder A Singh, Max H Epstein, Prathap Jayaram Jun 2020

Dynamic Ultrasound Uniquely Reveals Anterior Capsular Tear Communicating With Vastus Intermedius Fibers, Shiv J Patel, Jasvinder A Singh, Max H Epstein, Prathap Jayaram

Faculty, Staff and Students Publications

We present a case of an anterior capsular tear of the right knee in a previously healthy, active individual. The patient was a 31-year-old male seen one month after the onset of throbbing anterior right knee pain, which progressed to sharp suprapatellar pain over the next three months. Both dynamic ultrasound (US) and MRI were obtained. Dynamic US revealed a tear of the anterior capsule of the right knee complicated by a suprapatellar effusion communicating into the vastus intermedius fibers of the quadriceps tendon. However, these findings were not evident on MRI. In addition to discussing this unique pathology, we …


Dermatology Resident Training On Depression Screening: A Cross-Sectional Survey, Kaitlyn L Streight, Harry Dao, Soo Jung Kim Jun 2020

Dermatology Resident Training On Depression Screening: A Cross-Sectional Survey, Kaitlyn L Streight, Harry Dao, Soo Jung Kim

Faculty, Staff and Students Publications

Background

Many dermatologic diseases are implicated in the development of depression. Currently, there is no literature addressing the extent of dermatology residency training on depression screening.

Objective

Our study aimed to determine the extent of dermatology residency training on depression screening to potentially improve education in this area.

Methods

We designed a 12-question survey to assess the level of resident training and comfort in depression screening for patients with acne vulgaris, atopic dermatitis, psoriasis, hidradenitis suppurativa, and skin cancer. Fifty-six residents completed the survey, and data for each question was analysed in aggregate.

Results

Participants found depression screening most important …


Frequency Of Monocyte Subsets Is Linked To The Severity Of Atherosclerosis In Patients With Ischemic Heart Disease: A Case-Control Study, Irina V. Kologrivova, Tatiana Suslova, Olga Koshelskaya, Oksana Trubacheva, Olga Haritonova, Irina Vinnitskaya Jun 2020

Frequency Of Monocyte Subsets Is Linked To The Severity Of Atherosclerosis In Patients With Ischemic Heart Disease: A Case-Control Study, Irina V. Kologrivova, Tatiana Suslova, Olga Koshelskaya, Oksana Trubacheva, Olga Haritonova, Irina Vinnitskaya

BioMedicine

Background: Monocytes are recognized as central cells in the progression of atherosclerosis, and are subcategorized into classical (CD14++CD16lo), intermediate (CD14++CD16hi) and non-classical (CD14+CD16hi) subsets.

Purpose: The present study aimed to assess the relationships between different subsets of monocytes, metabolic and inflammatory factors in patients with stable coronary heart disease.

Methods: A total of 26 patients (both men and women) with stable ischemic heart disease (IHD). Among all the recruited patients, 17 patients had significant coronary artery disease defined as diameter stenosis more than 70%. Severity of CHD was assessed by the Gensini score (GS). …


Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria Jun 2020

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …


Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani Jun 2020

Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A …


Acute Tubular Injury In A Patient On A Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor, June K Pickett, Maulin Shah, Michael Gillette, Peter Jones, Salim Virani, Christie Ballantyne, Vijay Nambi Jun 2020

Acute Tubular Injury In A Patient On A Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor, June K Pickett, Maulin Shah, Michael Gillette, Peter Jones, Salim Virani, Christie Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

A 72-year-old man with coronary artery disease, statin intolerance, and chronic kidney disease stage IIIa was initiated on alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, and developed acute kidney injury. A kidney biopsy was performed and suggested acute tubular injury. The serum creatinine returned to baseline after discontinuation of alirocumab. (Level of Difficulty: Intermediate.)


Multi-Community Cardiopulmonary Resuscitation Education By Medical Students, Kenton L Anderson, Kian Niknam, Larry Laufman, Stefanie S Sebok-Syer, Sara Andrabi Jun 2020

Multi-Community Cardiopulmonary Resuscitation Education By Medical Students, Kenton L Anderson, Kian Niknam, Larry Laufman, Stefanie S Sebok-Syer, Sara Andrabi

Faculty, Staff and Students Publications

Introduction One purpose of the hands-only cardiopulmonary resuscitation (HOCPR) program is to simplify CPR instruction to encourage more bystanders to take action during cardiac arrest. Although the program has been successfully implemented in traditional classroom settings, the utility of large-scale training events has not been well-explored. We hypothesized that CPR knowledge and comfort levels would increase through a large-scale, multi-community HOCPR training event. We also explored what effect this training event had on perceived barriers to bystander-performed CPR. Methods A convenience sample participated in HOCPR training on a single day across 10 Texas cities. A sub-sample completed training questionnaires, including …


A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei Jun 2020

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.


Systemic Proteome Alterations Linked To Early Stage Pancreatic Cancer In Diabetic Patients, Hong Peng, Sheng Pan, Yuanqing Yan, Randall E Brand, Gloria M Petersen, Suresh T Chari, Lisa A Lai, Jimmy K Eng, Teresa A Brentnall, Ru Chen Jun 2020

Systemic Proteome Alterations Linked To Early Stage Pancreatic Cancer In Diabetic Patients, Hong Peng, Sheng Pan, Yuanqing Yan, Randall E Brand, Gloria M Petersen, Suresh T Chari, Lisa A Lai, Jimmy K Eng, Teresa A Brentnall, Ru Chen

Faculty, Staff and Students Publications

BACKGROUND: Diabetes is a risk factor associated with pancreatic ductal adenocarcinoma (PDAC), and new adult-onset diabetes can be an early sign of pancreatic malignancy. Development of blood-based biomarkers to identify diabetic patients who warrant imaging tests for cancer detection may represent a realistic approach to facilitate earlier diagnosis of PDAC in a risk population.

METHODS: A spectral library-based proteomic platform was applied to interrogate biomarker candidates in plasma samples from clinically well-defined diabetic cohorts with and without PDAC. Random forest algorithm was used for prediction model building and receiver operating characteristic (ROC) curve analysis was applied to evaluate the prediction …


Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani Jun 2020

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …


Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest Jun 2020

Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest

Theses and Dissertations (ETD)

While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. …


Ipledge Must Abstain From Abstinence, Kami Lowery, Theodore Rosen, Janet Malek Jun 2020

Ipledge Must Abstain From Abstinence, Kami Lowery, Theodore Rosen, Janet Malek

Faculty, Staff and Students Publications

Isotretinoin has unmatched efficacy in the treatment of acne. However, because isotretinoin is a teratogen that can cause profound birth defects, the iPLEDGE program regulates the drug's distribution in the United States. To minimize fetal exposure to isotretinoin, the program requires that female patients capable of becoming pregnant use two forms of contraception or commit to abstinence while using this therapy. This manuscript argues that iPLEDGE should be revised to remove abstinence as an acceptable contraceptive option in the face of evidence that disputes its efficacy. All patients, regardless of reported sexual activity, should be required to use data-proven contraception. …


Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray Jun 2020

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …


Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang May 2020

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …


A Rare Clinical Presentation Of Metastatic Crohn's Disease, Kaitlyn L Streight, Tara L Braun, Nicholas Lowe, Soo Jung Kim May 2020

A Rare Clinical Presentation Of Metastatic Crohn's Disease, Kaitlyn L Streight, Tara L Braun, Nicholas Lowe, Soo Jung Kim

Faculty, Staff and Students Publications

A 31-year-old female with a history of systemic lupus erythematous, IgA nephropathy, and psoriasis presented with a one-month history of a painful, pruritic rash under the bilateral breasts and in the genital region. Cutaneous examination revealed a large, tender ulcer under the left breast with a shiny erythematous base and peripheral hypertrophic changes. Small ulcers were present on the bilateral inguinal folds, and the labia majora were edematous with multiple erythematous papules. Histological examination of the left breast revealed ulceration with granulomatous dermatitis, consistent with a diagnosis of metastatic Crohn's disease. Metastatic Crohn's disease is a rare cutaneous manifestation of …


Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox May 2020

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …


Similac Special Care And Elecare Cause Neonatal Gut Injury In Mice, Karishma Rao, Heather L. Menden, Wei Yu, Inamul Haque, Susana Chavez-Bueno, Alain C. Cuna, Shahid Umar, Venkatesh Sampath May 2020

Similac Special Care And Elecare Cause Neonatal Gut Injury In Mice, Karishma Rao, Heather L. Menden, Wei Yu, Inamul Haque, Susana Chavez-Bueno, Alain C. Cuna, Shahid Umar, Venkatesh Sampath

Research Days

No abstract provided.


Clinical Validation And Diagnostic Rate/Outcomes Of A Dual Molecular Diagnostic Assay For Myotonic Dystrophy 1., Maxime Cadieux-Dion, Isabelle Thiffault, Midhat S. Farooqi, Joseph Alaimo May 2020

Clinical Validation And Diagnostic Rate/Outcomes Of A Dual Molecular Diagnostic Assay For Myotonic Dystrophy 1., Maxime Cadieux-Dion, Isabelle Thiffault, Midhat S. Farooqi, Joseph Alaimo

Research Days

No abstract provided.


Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt May 2020

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …


The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell May 2020

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …


The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma May 2020

The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma

Theses & Dissertations

Sympatho-excitation is a key characteristic in cardiovascular diseases such as chronic heart failure (CHF) and primary Hypertension (HTN). Evidence suggests that increased sympathetic tone is closely related to activation of the Renin-Angiotensin-Aldosterone system (RAAS) in the central nervous system. An underlying mechanism for sympatho-excitation is thought to be oxidative stress resulting from Angiotensin II (AngII) type 1 receptor (AT1R) activation. Over the past several decades, pharmacological targeting of components of the RAAS have been used as standard therapy in CHF and HTN. However, additional therapeutic strategies are necessary to control these diseases. Oxidative stress is regulated, in part, by the …


How Can We Stop Cancer?, Joseph R. Current May 2020

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …


The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes May 2020

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …


An Investigation Of Treatments For The Prevention Of Metabolic Complications For Women Suffering From Polycystic Ovarian Syndrome: Diet, Exercise, Weight Reduction And Herbal Remedies, Brenda Martinez-Puente May 2020

An Investigation Of Treatments For The Prevention Of Metabolic Complications For Women Suffering From Polycystic Ovarian Syndrome: Diet, Exercise, Weight Reduction And Herbal Remedies, Brenda Martinez-Puente

Nursing | Senior Theses

The purpose of this research study is to compare the views of traditional versus alternative treatments available to women with Polycystic Ovarian Syndrome (PCOS) suffering from metabolic complications. Alternative treatments include diet, exercise, herbal remedies, or any combination of the three. Pharmacological interventions for the conditions associated with PCOS such as metformin, used to control glucose levels, and clomiphene, used to treat infertility. Through the literature review, articles show herbs and plant products to have similar mechanisms of actions as the pharmacological interventions, but with less side effects. For example, cinnamon was shown to increase insulin sensitivity and pomegranate juice …


The Evil Twin: The Case Of Heterotopic Pregnancy, Rashmi Jadhav, Vegas Brown, Gabriel Cabrera May 2020

The Evil Twin: The Case Of Heterotopic Pregnancy, Rashmi Jadhav, Vegas Brown, Gabriel Cabrera

West Florida Division GME Research Day 2020

  • Heterotopic pregnancy occurs in about 1 in 30,000 naturally conceived pregnancies (5). The risk rises 1-3% for pregnancies occurring through assisted reproductive technologies (ART) (1).
  • Isolated ectopic pregnancy affects an average of 1 in every 150 live births (1).
  • A known pre-existing intrauterine pregnancy (IUP) can be falsely reassuring and delay the diagnosis of a potentially life-threatening concurrent ectopic pregnancy.
  • Presentation is vague and 45% of patients have no symptoms (5).
  • Differential Diagnoses: endometritis, incomplete miscarriage, ruptured ovarian cyst, non-GYN cause (ie: appendicitis or UTI).
  • Risk Factors: Infertility treatment, in vitro fertilization (IVF), prior ectopic, prior tubal surgery, use of …