Medicine and Health Sciences Commons^™

Ifrd1 Is Required For Maintenance Of Bladder Epithelial Homeostasis, Bisiayo E Fashemi, Amala K Rougeau, Arnold M Salazar, Steven J Bark, Rayvanth Chappidi, Jeffrey W Brown, Charles J Cho, Jason C Mills, Indira U Mysorekar

Faculty, Staff and Students Publications

The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern. We show that IFRD1 interacts with mRNA-translation-regulating factors in human urothelial cells. Loss of Ifrd1 leads to disrupted proteostasis, enhanced endoplasmic reticulum (ER stress) with activation of the PERK arm of the unfolded protein response pathway, …

Rna-Dependent Rna Polymerase Of Predominant Human Norovirus Forms Liquid-Liquid Phase Condensates As Viral Replication Factories, Soni Kaundal, Ramakrishnan Anish, B Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E Crawford, Jeroen Pollet, Fabio Stossi, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoVs) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide. Here, we show that the RNA-dependent RNA polymerase (RdRp) of pandemic GII.4 HuNoV forms distinct condensates that exhibit all the signature properties of LLPS with sustained polymerase activity and the capability of recruiting components essential for viral replication. …

Implementing The Morisky Medication Adherence Scale To Improve Medication Adherence In Patients With Hiv And Mental Illness, Kyle Ransom

Doctor of Nursing Practice Final Project Abstract

PURPOSE The purpose of this scholarly project was to implement a standardized process for assessing patient medication adherence through the use of a high-quality self-report questionnaire.

BACKGROUND The project was implemented at a federally funded outpatient HIV specialty clinic.

METHODOLOGY Patients seen by the clinic’s psychiatric/mental health nurse practitioners completed the Morisky Medication Adherence Scale during the nurse triage encounter. Patients who scored poorly (below 6) were then referred to the clinic’s interprofessional team (e.g., social workers and pharmacists) to address barriers to medication adherence. Medication adherence was measured using data collected from the on-site pharmacy records in order to …

Womb, Gravity, And Space: Shifting Towards The Cerebellum-Basal Ganglia Paradigm In Dystonia, Diego Iacono

Department of Neurology Faculty Papers

No abstract provided.

Prospective, Crossover, Comparative Study Of Two Methods Of Chlorhexidine Bathing, Richard J. Hankins

Theses & Dissertations

Bathing intensive care unit (ICU) patients with chlorhexidine gluconate (CHG) decreases hospital acquired infections (HAIs). The optimal method of CHG bathing remains undefined. Prospective cluster crossover study comparing CHG daily bathing with 2% CHG impregnated cloths versus 4% CHG solution. In phase 1, from January 2020 through March 2020, one ICU utilized 2% cloths, while the other ICU utilized 4% solution. After an interruption caused by the COVID-19 pandemic, in phase 2, from July 2020 through September 2020, the unit CHG bathing assignments were reversed. Swabs were performed three times per week from patients’ arms and legs to measure skin …

Fda Approval Of Zuranolone: A Breakthrough Treatment For Postpartum Depression, Connor Dains, Makayla Eversole, Kiley Devoll, Daniella Egbujor, Marisa Petrunich, Madilyn Paphanchith, Joshua Honaker, Samantha Mccord, Manoranjan D'Souza

Pharmacy and Wellness Review

Postpartum depression (PPD) is a serious medical condition that increases the risk of postpartum mortality and affects the ability of a postpartum individual to take care of their newborn. Until 2023, intravenously-administered brexanolone was the only Food and Drug Administration (FDA)-approved medication for PPD. Brexanolone’s route of administration poses significant barriers to accessibility and convenience. Other treatment options, such as psychotherapy and antidepressants, often require long-term commitment and may not provide rapid relief for severe symptoms. In August 2023, the FDA approved zuranolone as an oral medication for PPD, which enhances treatment accessibility and offers patients a more flexible, outpatient …

From Policymaking To Legislation, The Need For A Secular Turn In Bioethics Discourse To Uphold, As A Function Of The Greater Good, Policy For Legislation Of Medically Aided Dying In The United States Of America, Scott Dyer

Electronic Theses and Dissertations

A person’s right to self-determination is a central aspect of living in a democratic nation. Similarly, decisions regarding medical care are generally left up to the patient to determine what treatment is or is not appropriate. The same should apply to end-of-life care as well, especially when a patient desires to hasten his or her death via medically aided dying. However, due to the illegality of medically assisted dying in most of the United States, the right to a self-determined death is not possible for the majority of American citizens. One of the main reasons for this is due to …

Mathematical Multi-Compartment Modeling Of Chronic Lymphocytic Leukemia Cell Kinetics Under Ibrutinib, Melanie Schulz, Sanne Bleser, Manouk Groels, Dragan Bošnački, Jan A Burger, Nicholas Chiorazzi, Carsten Marr

Faculty, Staff and Student Publications

The Bruton tyrosine kinase inhibitor ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia (CLL). While it rapidly reduces lymph node and spleen size, it initially increases the number of lymphocytes in the blood due to cell redistribution. A previously published mathematical model described and quantified those cell kinetics. Here, we propose an alternative mechanistic model that outperforms the previous model in 26 of 29 patients. Our model introduces constant subcompartments for healthy lymphocytes and benign tissue and treats spleen and lymph nodes as separate compartments. This three-compartment model (comprising blood, spleen, and lymph nodes) performed significantly better …

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Protocol For Monitoring Clonal Hematopoiesis In Transgenic Mouse Models Using Multispectral Imaging, Priyanka Khanna, Lauren B Ostermann, Shayaun Khazaei, Ran Zhao, Michael Andreeff, Rasoul Pourebrahim

Faculty, Staff and Student Publications

Clonal hematopoiesis involves the clonal expansion of hematopoietic cells, potentially progressing into hematological malignancies. Here, we present a protocol for the development and characterization of two mouse models designed to simulate clonal hematopoiesis and acute myeloid leukemia. We describe steps for model generation, monitoring clonal expansion, harvesting, fixation, and staining of bone marrow and spleen tissues. We specifically focus on the visualization and analysis of p53 mutant clonal expansions, providing a comprehensive protocol for studying these phenomena in mouse models. For complete details on the use and execution of this protocol, please refer to Pourebrahim et al.

Survival Analysis Of Clear Cell Renal Cell Carcinoma Based On Radiomics And Deep Learning Features From Ct Images, Zhennan Lu, Sijia Wu, Dan Ni, Meng Zhou, Tao Wang, Xiaobo Zhou, Liyu Huang, Yu Yan

Faculty, Staff and Student Publications

Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.

Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator. Then the selected features formed a fusion signature, which was assessed by Cox proportional hazard regression model method, Kaplan-Meier analysis, receiver operating characteristic curves, and concordance index (C-index) …

Specifically Targeting Muc16 For Fluorescence-Guided Surgery Of Pancreatic Ductal Adenocarcinoma, Kathryn M. Muilenburg

Theses & Dissertations

Pancreatic cancer is a lethal disease with a low 5-year survival rate and a high rate of resection recurrence. However, surgery remains the only treatment with curative potential for pancreatic cancer. Many factors such as high desmoplasia, a lack of intraoperative imaging, and micrometastatic disease contribute to the high rate of incomplete resections in pancreatic cancer. Fluorescence-guided surgery (FGS) is a potential intraoperative tool for application in surgical resection. FGS works through passive or active targeting of a free dye or dye-containing moiety (e.g. antibody, peptide, and nanoparticles) to specifically fluoresce the tumor compared to the surrounding normal, fibrotic, and …

Formulation And Characterization Of Biologics – From Sirna To Monoclonal Antibodies, Chinmay M. Jogdeo

Theses & Dissertations

Biologics are a rapidly growing class of therapeutics, encompassing a wide range of modalities, with gene therapy products and monoclonal antibodies (mAbs) constituting the majority. Proper formulation and characterization of these complex therapeutics is crucial to ensure their safety and therapeutic efficacy.

This dissertation focuses on two main areas: the development of a novel renal-targeted siRNA delivery system and the assessment of structural and conformational stability of mAbs in a simulated subcutaneous (SC) environment.

The first part of this dissertation presents the synthesis and characterization of a novel renal-targeted polymer for selective siRNA delivery to injured kidneys. Inulin was modified …

Bio-Preparedness In A Global Context: Multi-Site International Study Investigating Global Health Security Challenges In Egypt, Oman, And The United States, Rima M. Al Balushi

Theses & Dissertations

The COVID-19 pandemic exposed myriad vulnerabilities globally within public health systems, from inadequate bio-risk management in laboratories to overwhelming utilization of hospital resources and disparities in vaccine access and uptake. The Global Health Security Index (GHSI), which critically evaluates health security domains including health systems and risk environments, reports serious weaknesses in global health security. This dissertation aims to investigate critical aspects of global health security domains by examining factors impacting biosafety and biosecurity capacities in laboratories in Egypt, healthcare resource utilization in hospitals in Oman relating to acute respiratory infections (ARI), and COVID-19 vaccine uptake in the United States. …

Ifrd1 Is Required For Maintenance Of Bladder Epithelial Homeostasis, Bisiayo E Fashemi, Amala K Rougeau, Arnold M Salazar, Steven J Bark, Rayvanth Chappidi, Jeffrey W Brown, Charles J Cho, Jason C Mills, Indira U Mysorekar

2020-Current year OA Pubs

The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern. We show that IFRD1 interacts with mRNA-translation-regulating factors in human urothelial cells. Loss of

Protocol For A Non-Surgical Model Of Perineural Invasion For Assessing Neural Drivers Of Cancer Aggressiveness In Mice, Tiago H Zaninelli, Telma Saraiva-Santos, Brielle H Patlin, Michael Slade Stratton, David Y Chen, Felipe A Pinho-Ribeiro

2020-Current year OA Pubs

Perineural invasion (PNI) is a significant risk factor for cancer recurrence and metastasis; however, its mechanisms relating to cancer aggressiveness remain poorly understood. Here, we present a protocol for a non-surgical model of PNI in mice using a neurotropic melanoma cell line that migrates from the skin to the sciatic nerve. We describe the steps for cell culture and injection, tumor burden measurements, mouse euthanasia, and tissue dissection. We then detail procedures for sample cross-section and confocal imaging.

The Plasmodium Falciparum Ncr1 Transporter Is An Antimalarial Target That Exports Cholesterol From The Parasite's Plasma Membrane, Zhemin Zhang, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria,

Bile Acids In Inflammatory Bowel Disease: From Pathophysiology To Treatment, Samantha H Bai, Arun Chandnani, Siyan Cao

2020-Current year OA Pubs

Inflammatory bowel disease (IBD) is a chronic condition that affects about 7 million people worldwide, and new therapies are needed. Understanding the complex roles that bile acids (BAs) play in IBD may lead to the development of novel IBD treatments independent of direct immunosuppression. This review discusses the latest discoveries in the roles BAs play in IBD pathogenesis and explores how these discoveries offer promising new therapeutic targets to treat IBD and improve patient outcomes. Several therapies discussed include specific BA receptor (BAR) agonists, dietary therapies, supplements, probiotics, and mesenchymal stem cell therapies that have all been shown to decrease …

Protocol For Culturing Patient-Derived Organoids Of Cervical Cancer, Rui Wang, Timothy Harris, Dalissa Negrón-Figueroa, David Lo, Allison Judge, D'Shaunique Walters, Bo Jiang, Lauren E Colbert

Faculty, Staff and Student Publications

Herein, we present a protocol for culturing patient-derived organoids (PDOs) of cervical cancer that includes workflows for tumor biopsy/resection tissue and cytobrush-sampled cells. We describe steps for PDO culture initiation, including rinsing, gentle dissociation, Lymphoprep separation, and cell assessment, as well as seeding cells from surgical and cytobrush tissue digestion. We then provide guidance on PDO maintenance and passage and techniques for producing conditioned medium. Overall, this protocol serves as a valuable guide for establishing and maintaining cervical cancer PDOs. For complete details on the use and execution of this protocol, please refer to Colbert et al.

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al.

2020-Current year OA Pubs

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous …

Pancreaticoduodenectomy In Trauma Patients With Grade Iv-V Duodenal Or Pancreatic Injuries: A Post Hoc Analysis Of An East Multicenter Trial, Rachel Leah Choron, Rami Al-Aref, Jordan Michael Kirsch, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV-V pancreaticoduodenal injuries.

METHODS: This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020. Included patients were ≥15 years of age with the American Association for the Surgery of Trauma grade IV-V duodenal and/or pancreatic injuries. The study compared operative repair strategy: PD versus non-PD.

RESULTS: The sample (n=95) was young (26 years), male (82%), …

Clinical Applications Of Phenomenology: Analysis Of Lived Experience Of Eye Disease, Kimberly Tucker

Graduate Student Research Symposium

This paper presents a phenomenological study that explores the embodied experience of vision loss within the context of eye disease, while also providing a detailed discussion of the methodological approaches utilized in the research. Phenomenology is integrated to address clinical epistemic concerns, particularly the limitations of conventional vision tests in fully capturing perception and the lived experiences of vision loss. This interdisciplinary approach builds on the clinical understanding of eye disease by incorporating the broader dimensions of the lifeworld that intersect with visual impairment in degenerative eye diseases. While standard clinical approaches focus primarily on measurable aspects of visual function, …

Dental Hygiene Program Feasibility In Kailua Kona, Hawaii, William Li, Lindsay Gietzen

Pacific Journal of Health

Establishing a dental hygiene program in Kailua Kona, Hawaii, could address critical gaps in local healthcare but requires careful consideration of its feasibility given the significant costs involved. This literature review assesses existing studies to understand the potential for success, focusing on effective recruitment and retention strategies that have been implemented in other rural and underserved regions. Findings reveal that communities worldwide face similar challenges in attracting healthcare providers to remote areas, with successful programs often integrating mandatory externships to encourage healthcare workers to experience and engage with underserved communities. Given Hawaii’s diverse ethnic makeup, insights from cross-cultural and global …

Learning To Be An Autistic Therapist: Personal Steps Towards An Autism-Affirming Psychotherapy, Sasha D. Strong

Ought: The Journal of Autistic Culture

How can Autistic therapists understand and support themselves, and how can this help them support their clients? In this paper, I recount my personal journey of healing and growth as an Autistic psychotherapist, 16 months after self-identification. Here is an overview of conceptual frameworks from #actuallyautistic authors, critical theory, queer theory, and social justice that I have found helpful. I also share some of the therapeutic and wellness approaches that have been important to me, including mindfulness and bodyfulness. Organic knowing has been pivotal for me in discerning between masking and aliveness, and regaining a choice around masking behaviors. This …

A Symphony Of Distractions, Alisha M. White

Ought: The Journal of Autistic Culture

No abstract provided.

Quality Improvement In Healthcare: A Practical Guide For Providers (Part 5), Jeremy Ellis Md

Transformative Medicine

No abstract provided.

Glp-1 Agonists For Weight Loss And Beyond, Connor Quinter, Hanh Motilall, Kelley Maberry

Transformative Medicine

Glucagon-like peptide-1 (GLP-1) agonists are medications that were originally approved for type 2 diabetes to help improve glycemic control in conjunction with exercise and dieting. One of the beneficial effects of this medication class is weight loss, and recently the FDA has approved a select few for this indication of weight loss. With these medications becoming increasingly more popular, it is imperative that both providers and patients understand the differences in terms of efficacy for these medications and the potential adverse events to make the best decision about initiating therapy. This article summarizes the FDA indications for all the GLP-1 …

Decoding 2:1 Atrioventricular Block, Jaswanth Jasti Md, Muhammad Asad Hanif Md, Muhammad Mohsin Zafar Md

Transformative Medicine

No abstract provided.

Initiation Of A Skills-Based "Boot Camp" Orientation For Incoming Ob/Gyn Resident Physicians, Nathanael N. Hoskins, Morgan Scheffler, Tammy Trace, Holly Metzgar

Transformative Medicine

Background: Residency orientations are often focused on administrative obligations and less often focused on program-specific skills training. Introduction of these skills during the orientation period has been shown to improve resident confidence and proficiency. The purpose of this quality improvement project is to propose the introduction of a skills-focused portion of orientation in a condensed “boot camp” fashion to improve the transition to residency from medical school.

Methods: The skills-based orientation curriculum was developed by reviewing the Accreditation Council for Graduate Medical Education (ACGME) milestones and prior literature on the topic. The simulations were planned using resident and faculty collaboration. …