Medicine and Health Sciences Commons^™

The Multifaceted Role Of Neutrophils In Nsclc In The Era Of Immune Checkpoint Inhibitors, Shucheng Miao, Bertha Leticia Rodriguez, Don L Gibbons

Faculty, Staff and Student Publications

Lung cancer is the most common cause of cancer-related death in both males and females in the U.S. and non-small-cell lung cancer (NSCLC) accounts for 85%. Although the use of first- or second-line immune checkpoint inhibitors (ICIs) exhibits remarkable clinical benefits, resistance to ICIs develops over time and dampens the efficacy of ICIs in patients. Tumor-associated neutrophils (TANs) have an important role in modulating the tumor microenvironment (TME) and tumor immune response. The major challenge in the field is to characterize the TANs in NSCLC TME and understand the link between TAN-related immunosuppression with ICI treatment response. In this review, …

Implementation Of The Process Improvement Toolkit For Hospital Acquired Pressure Injuries, Christina Bearden

Dissertations

Problem: Approximately 2.5 million people within the United States receiving inpatient medical care will develop a pressure injury each year (Padula & Demarmente, 2018). Pressure injuries (PI) are a multifactorial complication that can often be avoided with general prophylactic measures. Despite this, inpatient settings around the United States continue to see a rise in PIs.

Method: The quality improvement initiative utilized a descriptive, observational design. The turn team toolkit was implemented and monitored over a two-month period. Patient descriptors and quantitative data were collected through a retrospective chart review. The primary data collected was on pressure injury rates and staff …

Evaluation Of A Smoking Cessation Program In Primary Care, Yolanda Duncan-Watt

Dissertations

Abstract

Problem: The adult tobacco smoking rate exceeds 12.5%. The problem is the insufficient attention given to smoking cessation education in low socioeconomic status(SES) communities. There is a lack of access to and awareness of smoking cessation programs for low-income populations.

Methods: This quality improvement (QI) study will use a descriptive, observational approach. A retrospective medical record review will be conducted to determine the rate of individuals who got the smoking cessation intervention and the rate of those who successfully quit one month after the intervention. Data was collected throughout the spring of 2024, during primary care visits and phone …

Improving Nurse Response To Seizure Events In A Pediatric Epilepsy Monitoring Unit With Use Of A Standardized Process, Stacey Obst Paule

Dissertations

Problem: Nurses responding to seizure events in the pediatric epilepsy monitoring unit (EMU) should initiate a neurological exam in addition to managing seizure activity. When nurses respond to these events, however, there can be significant variability, which can result in diagnostic inaccuracy and adverse patient outcomes. The purpose of this project is to implement a nursing response checklist and neurological assessment guide to standardize the process of response to seizure events in the pediatric EMU.

Methods: This quality improvement (QI) project utilized a cohort study design. Standardized tools were placed in an accessible area outside patient rooms. Education was provided …

Implementation Of Skin-To-Skin Immediately Post C-Section: A Pilot Study, Miah Vernor

Dissertations

Skin-to-skin contact during the golden hour is a practice that has numerous health benefits following the delivery of a newborn. These benefits include a healthy transition to extrauterine state, initiation of breastfeeding, thermoregulation, and more. However, the mode of delivery affects how often this practice is done. Parents who deliver vaginally are routinely offered the opportunity to perform skin-to-skin immediately after delivery whereas birth parents who deliver by cesarean section are not always offered this same benefit due to various reasons. A quality improvement project was conducted on an 18-bed labor and delivery unit at a Midwest hospital. This project …

Implementation Of Skin-To-Skin Contact Immediately Post Cesarean Birth: A Quality Improvement Project, Sophia Cooke

Dissertations

Problem: Skin-to-skin contact implemented within the first hour of a newborn’s life improves health outcomes for both mother and infant. One of these health outcomes includes exclusive breastfeeding. The purpose of this quality improve project was to implement an infant securement device within the operating room after cesarean section births to decrease the time to initiate skin-to-skin contact and increase exclusive breastmilk feeding rates at discharge.

Methods: This study utilized a descriptive, observational design and was guided by the Plan-Do-Study-Act framework. A pre-test, post-test design was utilized to compared retrospective and prospective data. The retrospective data was collected to assess …

Evaluation Of The Grief Of Mothers Affected By Perinatal And Traumatic Loss, Landry Crabtree

Dissertations

Problem: The experience of a perinatal loss can be traumatic for mothers, and complicated grief reactions are common for those who have experienced a perinatal loss. An increase in perinatal loss resources is needed in the United States. The purpose of this program evaluation was to assess outcomes of a pilot perinatal loss support program on the grief of women who have experienced a perinatal loss.

Methods: This project was an evaluation of a perinatal loss support program that employed evidence-based strategies in both individual and group therapy sessions. A retrospective design was used, and data on perinatal …

Implementation Of Postnatal Depression Screening: A Pilot Study, Mollie Gulino

Dissertations

Abstract

Background: Postpartum depression (PPD) is a prevalent problem among women during their childbearing years, affecting approximately 1 in 7 women. Alarmingly, about 50% of PPD cases go undiagnosed and untreated, contributing to poor maternal outcomes, including suicide, which is a leading cause of maternal mortality in the United States.

Issue: Despite its prevalence and severe consequences, PPD often goes unrecognized due to inconsistent screening practices. Current guidelines vary by organization and lack consistent, evidence-based criteria.

Objective: This pilot program aimed to implement universal PPD screening with a validated tool at the six-week postpartum follow-up visit. The goal was to …

Implementation Of The Edinburgh Postpartum Depression Screening Tool For Postpartum Depression In A Midwest Primary Care Clinic, Makenzie Garrison

Dissertations

Problem: Postpartum depression is a prevalent health concern in postpartum women. Screening practices to identify postpartum depression are inconsistent. The purpose of this quality initiative is to determine if the implementation of the Edinburgh Postpartum Depression Screening Tool (EPDS) to screen for postpartum depression in the primary care setting increases the detection of postpartum depression in postpartum women from delivery to one year postpartum.

Methods: This quality improvement project utilizes a descriptive, observational design. A retrospective medical record review was utilized as well as a 12-week data collection period. Retrospective medical record reviews were conducted to assess the rate of …

Implementation Of Quantitative Blood Loss Following Cesarean Section Birth, Layna Victoria Schultz

Dissertations

Problems: Postpartum hemorrhage (PPH) is a significant problem due to potential harm and is a main contributor to maternal morbidity (ACOG, 2019). According to ACOG, of maternal deaths in the United States, 11% are caused by PPH and 54-93% of the deaths related to PPH could be prevented (ACOG, 2019). When institutions adopt quantitative blood loss (QBL) protocols for improved accuracy in blood measurement, PPH can be identified sooner, allowing for earlier intervention. Inaccurate estimation of obstetric blood loss by health care providers is a primary cause of delayed staff response to PPH (ACOG, 2019).

Methods: This quality improvement (QI) …

The History Of Diapers And Their Environmental Impact, Cansu Tokat, Nicholas C. Rickman, Cynthia F. Bearer

Faculty Scholarship

Impact: This article examines diaper practices around the world throughout history. This article reviews the innovation of the modern diaper and the environmental effects of disposable diapers.

The Effectiveness Of Technology And Smart-Home Based Teaching Modules For Direct Care Workers, Emily Demers, Andrea Mesbergen, Elise Kuiper, Jenna Prohaska, Lauren Czajka

Masters Projects

Little research has investigated the benefits of implementing technological devices in at-home environments for those with intellectual or developmental disabilities (IDD). Assistive technology has the capability to increase resident’s self-determination, communication, and overall independence in completing everyday tasks. This study explored the effects of training/education on the ongoing use of technology within the living space of those with IDD. The methodology for this study included a 2-part series of modules to teach direct care workers how to use and support their residents in using Amazon Alexa Show devices, Amazon Alexa Dot Devices, smart lights, and smart doorbells. The series included …

America Is Unprepared To Meet The Needs Of Its Growing Older Adult Population, Sierra Kaplan

Population Health Research Brief Series

In 2030, nearly 73 million Americans will be aged 65 years or older. As Americans continue to have fewer children than in the past, the number of older adults will outnumber children. Thus, fewer young adults will be around to support and care for the older adult population. Coupled with COVID-19 pandemic-driven disruptions to the healthcare industry, America’s health and aging care system is unprepared to support its large and growing older adult population. Over time, we will see increased health care scarcity and inequality in the distribution of elder care services, especially with continued healthcare worker shortages and drastic …

Persistent Interruption In Parvalbuminpositive Inhibitory Interneurons: Biophysical And Mathematical Mechanisms, Carol M. Upchurch, Christopher J. Knowlton, Simon Chamberland, Carmen C. Canavier

School of Graduate Studies Faculty Publications

Persistent activity in excitatory pyramidal cells (PYRs) is a putative mechanism for maintaining memory traces during working memory. We have recently demonstrated persistent interruption of firing in fastspiking parvalbumin-expressing interneurons (PV-INs), a phenomenon that could serve as a substrate for persistent activity in PYRs through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs. Modeling and mathematical analysis showed that the slowly inactivating potassium current KV1 contributes to type 2 excitability, enables the multiple firing regimes observed experimentally in PV-INs, and provides a mechanism for robust persistent interruption …

A Fungal Metabolic Regulator Underlies Infectious Synergism During Candida Albicans-Staphylococcus Aureus Intra-Abdominal Co-Infection, Saikat Paul, Olivia A. Todd, Kara R. Eichelberger, Christine Tkaczyk, Bret R. Sellman, Mairi C. Noverr, James E. Cassat, Paul L. Fidel, Brian M. Peters

School of Dentistry Faculty Publications

Candida albicans and Staphylococcus aureus are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) demonstrates that synergistic lethality is driven by Candida-induced upregulation of functional S. aureus α-toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of C. albicans transcription factor mutants was undertaken revealing that zcf13Δ/Δ fails to drive augmented α-toxin or lethal synergism during co-infection. A combination of transcriptional and phenotypic profiling approaches shows that ZCF13 regulates …

Progenitors Of Distinct Lineages Shape The Diversity Of Mature Type 2 Conventional Dendritic Cells, Patrick Fernandes Rodrigues, Tihana Trsan, Grozdan Cvijetic, Darya Khantakova, Santosh K Panda, Zhaoyuan Liu, Florent Ginhoux, Marina Cella, Marco Colonna

2020-Current year OA Pubs

Conventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8

Defining Primary Refractory Large B-Cell Lymphoma, Allison M Bock, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort. Patients with newly diagnosed LBCL were enrolled in the Molecular Epidemiological …

Displace Study Shows Poor Quality Of Transcranial Doppler Ultrasound For Stroke Risk Screening In Sickle Cell Anemia, Kimberly A Davidow, Robin E Miller, Shannon M Phillips, Alyssa M Schlenz, Martina Mueller, Monica L Hulbert, Lewis L Hsu, Neha Bhasin, Robert J Adams, Julie Kanter

2020-Current year OA Pubs

Children with sickle cell anemia (SCA) are at increased risk of stroke when compared with their age-based counterparts. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) previously demonstrated that with the use of transcranial Doppler ultrasound (TCD; Sickle Stroke Screen) and chronic red cell transfusion, the risk of stroke is reduced by over 90%. The STOP criteria detailed the type and method of measurement required; the time-averaged mean maximum velocity (TAMMV). Unfortunately, it has been difficult to adhere to the appropriate TAMMV measurements. The objectives of this study were to assess the quality of TCD and transcranial Doppler imaging …

Unraveling Facets Of Mecom-Associated Syndrome: Somatic Genetic Rescue, Clonal Hematopoiesis, And Phenotype Expansion, Parvathy Venugopal, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Cns Relapse In T-Cell Lymphoma Index Predicts Cns Relapse In Patients With T- And Nk-Cell Lymphomas, Rahul S Bhansali, Neha Mehta-Shah, Et Al.

2020-Current year OA Pubs

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. …

Attenuating Midline Thalamus Bursting To Mitigate Absence Epilepsy, Ping Dong, Konstantin Bakhurin, Yuhui Li, Mohamad A Mikati, Jianmin Cui, Warren M Grill, Henry H Yin, Huanghe Yang

2020-Current year OA Pubs

Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, …

Where Are We Now With Oncolytic Viruses In Melanoma And Nonmelanoma Skin Malignancies?, George Nassief, Angela Anaeme, Karen Moussa, David Chen, George Ansstas

2020-Current year OA Pubs

Skin cancer prognosis has greatly improved recently due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients with advanced skin cancer still experience immunotherapy resistance and disease progression during ICI treatment, thus calling for novel therapeutics which address this treatment gap. Talimogene laherparepvec (T-VEC) has gained popularity in recent years as a viable treatment option for patients with skin cancer. In preclinical studies, T-VEC demonstrated both a direct anti-tumor effect in injected lesions as well as a systemic immune-mediated effect in non-injected lesions, which could pose additional benefits when combined with ICI therapy. Following promising results from the …

Cxcl16-Dependent Scavenging Of Oxidized Lipids By Islet Macrophages Promotes Differentiation Of Pathogenic Cd8+ T Cells In Diabetic Autoimmunity, Neetu Srivastava, Hao Hu, Orion J Peterson, Anthony N Vomund, Marta Stremska, Mohammad Zaman, Shilpi Giri, Tiandao Li, Cheryl F Lichti, Pavel N Zakharov, Bo Zhang, Nada A Abumrad, Yi-Guang Chen, Kodi S Ravichandran, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

The pancreatic islet microenvironment is highly oxidative, rendering β cells vulnerable to autoinflammatory insults. Here, we examined the role of islet resident macrophages in the autoimmune attack that initiates type 1 diabetes. Islet macrophages highly expressed CXCL16, a chemokine and scavenger receptor for oxidized low-density lipoproteins (OxLDLs), regardless of autoimmune predisposition. Deletion of Cxcl16 in nonobese diabetic (NOD) mice suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency impaired clearance of OxLDL by islet macrophages, leading to OxLDL accumulation in pancreatic islets and a substantial reduction in intra-islet transitory (Tex

Incidence And Types Of Cardiac Arrhythmias In The Peri-Ictal Period In Patients Having A Generalized Convulsive Seizure, Laura Vilella, Christina Y Miyake, Ganne Chaitanya, Johnson P Hampson, Shirin Jamal Omidi, Manuela Ochoa-Urrea, Blanca Talavera, Oscar Mancera, Norma J Hupp, Jaison S Hampson, M R Sandhya Rani, Nuria Lacuey, Shiqiang Tao, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine A Scott, Brian Gehlbach, Stephan U Schuele, Jennifer A Ogren, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Students Publications

Background and objectives: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases.

Methods: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during …

Cotargeting Ebv Lytic As Well As Latent Cycle Antigens Increases T-Cell Potency Against Lymphoma, Sandhya Sharma, Naren U Mehta, Tim Sauer, Lisa A Rollins, Dirk P Dittmer, Cliona M Rooney

Faculty, Staff and Students Publications

The remarkable efficacy of Epstein-Barr virus (EBV)-specific T cells for the treatment of posttransplant lymphomas has not been reproduced for EBV-positive (EBV+) malignancies outside the transplant setting. This is because of, in part, the heterogeneous expression and poor immunogenicity of the viral antigens expressed, namely latent membrane proteins 1 and 2, EBV nuclear antigen 1, and BamHI A rightward reading frame 1 (type-2 [T2] latency). However, EBV lytic cycle proteins are also expressed in certain EBV+ malignancies and, because several EBV lytic cycle proteins are abundantly expressed, have oncogenic activity, and likely contribute to malignancy, we sought and identified viral …

Adjunctive Therapy With An Oral H2s Donor Provides Additional Therapeutic Benefit Beyond Sglt2 Inhibition In Cardiometabolic Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Huijing Xia, Xiaoman Yu, Alexandra R. Nevins, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Timothy D. Allerton, Mona Elgazzaz, Eric Lazartigues, Sanjiv J. Shah, Zhen Li, David J. Lefer

School of Graduate Studies Faculty Publications

Background and Purpose: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated. Experimental Approach: Nine-week-old C57BL/6N mice received L-NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten-week-old ZSF1 obese rats were randomized to control, SGLT2i or …

Morgs3 Functions In Intracellular Reactive Oxygen Species Perception-Integrated Camp Signaling To Promote Appressorium Formation In Magnaporthe Oryzae, Ruiming Zhang, Xinyu Liu, Jiayun Xu, Chen Chen, Zhaoxuan Tang, Chengtong Wu, Xinyue Li, Lei Su, Muxing Liu, Leiyun Yang, Gang Li, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Regulator of G-protein signaling (RGS) proteins exhibit GTPase-accelerating protein activities to govern G-protein function. In the rice blast fungus Magnaporthe oryzae, there is a family of at least eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), each exhibiting distinct or shared functions in the growth, appressorium formation, and pathogenicity. MoRgs3 recently emerged as one of the crucial regulators that senses intracellular oxidation during appressorium formation. To explore this unique regulatory mechanism of MoRgs3, we identified the nucleoside diphosphate kinase MoNdk1 that interacts with MoRgs3. MoNdk1 phosphorylates MoRgs3 under induced intracellular reactive oxygen species levels, and MoRgs3 phosphorylation is required for …

Electrocautery Wire Fenestration Prior To Thoracic Endovascular Aortic Repair To Optimize The Distal Landing Zone In Thoracic Aortic Dissections, Nicola Habash, Gaurang Joshi, Mohammed Ali, Michael Nooromid, Babak Abai

Department of Surgery Faculty Papers

Successful thoracic endovascular aortic repair (TEVAR) for type B aortic dissections (TBAD) relies on securing the stentgraft’s distal landing zone to prevent retrograde flow and false lumen pressurization. We describe a 60-year- old male with a TBAD undergoing TEVAR with electrocautery-wire fenestration of the dissection septum, providing a controlled method to enhance the distal landing zone for graft placement. Postoperatively, the patient experienced spinal cord ischemia, resolving with the placement of a lumbar drain and increasing mean arterial pressures. Follow-up imaging demonstrated a well-sealed repair without endoleaks. This case highlights the importance of surgical technique selection and postoperative monitoring for …

Tfeb Safeguards Trophoblast Syncytialization In Humans And Mice, Wanshan Zheng, Yue Zhang, Peiqun Xu, Zexin Wang, Xuan Shao, Chunyan Chen, Han Cai, Yinan Wang, Ming-An Sun, Wenbo Deng, Fan Liu, Jinhua Lu, Xueqin Zhang, Dunjin Cheng, Indira U Mysorekar, Haibin Wang, Yan-Ling Wang, Xiaoqian Hu, Bin Cao

Faculty, Staff and Students Publications

The formation of multinucleated syncytiotrophoblast (STB) through cell fusion of cytotrophoblast, also termed syncytialization, ensures the proper placental structure and functions. Nutrient insufficiency and inactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in trophoblasts have been shown to enhance STB formation; however, the underlying mechanism remains elusive. Here, we showed that the deficiency of a mTORC1 downstream transcriptional factor, TFEB, significantly impaired STB formation in human trophoblasts and knock-out mice. TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 and thereby promoted trophoblast syncytialization. Additionally, TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth …

Bempedoic Acid Falls In Line, Maya S Safarova, Patrick M Moriarty, Iftikhar J Kullo, Christie M Ballantyne, Eugenia Gianos

Faculty, Staff and Students Publications

No abstract provided.