Medicine and Health Sciences Commons^™

Age-Related Tfeb Downregulation In Proximal Tubules Causes Systemic Metabolic Disorders And Occasional Apolipoprotein A4-Related Amyloidosis, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Satoshi Minami, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Hideaki Kawai, Isao Matsui, Tadashi Yamamuro, Ryuya Edahiro, Seiji Takashima, Akira Takasawa, Yukinori Okada, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy/lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly patients with CKD remains unknown. First, we found that nuclear TFEB localization in proximal tubular epithelial cells (PTECs) declined with age in both mice and humans. Next, we generated PTEC-specific Tfeb-deficient mice and bred them for up to 24 months. We found that TFEB …

Deuterated Water Labeling In Ibrutinib-Treated Patients With Cll: Leukemia Cell Kinetics Correlate With Ighv, Zap-70, And Mrd, Ekaterina Kim, Shih-Shih Chen, Mariela Sivina, Hyunsoo Hwang, Xuelin Huang, Alessandra Ferrajoli, Nitin Jain, William G Wierda, Dominik Wodarz, Nicholas Chiorazzi, Jan A Burger

Faculty, Staff and Student Publications

Deuterated (“heavy”) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.

The Proteomics Of T-Cell And Early T-Cell Precursor (Etp) Acute Lymphocytic Leukemia: Prognostic Patterns In Adult And Pediatric-Etp All, Fieke W Hoff, Lourdes Sriraja, Yihua Qiu, Gaye N Jenkins, David T Teachey, Brent Wood, Meenakshi Devidas, Shaina Shockley, Mignon L Loh, Evangelia Petsalaki, Steven M Kornblau, Terzah M Horton

Faculty, Staff and Student Publications

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Methods: Protein expression was assessed using RPPA methodology for 321 target proteins in 361 T-ALL patient samples from 292 pediatrics and 69 adults, …

Enhancer Reprogramming Underlies Therapeutic Utility Of A Smarca2 Degrader In Smarca4 Mutant Cancer, Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu

Faculty, Staff and Student Publications

Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog SMARCA2 is synthetic lethal to SMARCA4 suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in SMARCA4-mutant cells with loss of chromatin accessibility at enhancers of genes …

Promoting The Use Of Suicide Prevention Mobile Applications Among Clinicians To Reduce Suicide & Suicidal Behaviors In Adults Aged 18-45, Papetua Jepkoech Kimutai

Doctoral Dissertations and Projects

Suicide among adults aged 18-45 has increased significantly and has become a challenge to public health worldwide. The purpose of this scholarly project was to promote the use of suicide prevention mobile applications by clinicians to reduce suicide and suicidal behaviors among adults (18-45 years old). Safety Plan suicide prevention mobile app was used in addition to the standard method of preventing suicide. A quasi-experimental design was conducted to promote a suicide prevention mobile app in clinical practice. The clinician participants included three family nurse practitioners (FNPs) and five psychiatric mental health nurse practitioners (PMHNPs)The data were collected using pre …

Improving Early Detection Of Skin Cancer Through Enhanced Screening Practices, Ashley Cline

Doctoral Dissertations and Projects

With an effort to enhance early detection and intervention, this research investigates the urgent need for better skin cancer screening procedures. Developing and evaluating a multicomponent intervention to improve skin cancer screening and increase skin cancer early detection rates in primary care settings was the purpose of this project. In order to assess the use of improved screening procedures for early skin cancer detection in the primary care setting at the Complete Health organization’s Ormond Beach branch, the evidence-based practice study used a quasi-experimental approach. The project focused on the clinical question of whether implementing enhanced screening practicessuch as patient …

Hormone Therapy Among Women Within A Clinical Setting: Health Literacy And Teach Back Method To Increase Understanding Of Potential Benefits And Risks Of Treatment, Mariah L. Petersen

Doctoral Dissertations and Projects

The purpose of this project was to examine hormonal therapy among women between the ages of 40 and 55 within a clinical setting. This project assessed women’s understanding of hormonal therapy for various treatments as well as the risks. The intervention utilized the teach-back method. The project also included the 10 essential elements the provider needs to be competent in the teach-back method. A pre- and post-test were given to patients to measure improvement of knowledge and understanding. The goal is to improve patients’ understanding of these treatments and to help them ask questions if they do not fully understand …

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …

Multimodal Oculomotor Assessment Reveals Prodromal Markers Of Parkinson's Disease In Non-Manifesting Lrrk2 G2019s Mutation Carriers, Heidi C Riek, Naomi P Visanji, Isabell C Pitigoi, Daniel G Di Luca, Laura Armengou-Garcia, Nazish Ahmed, Julia E Perkins, Donald C Brien, Jeff Huang, Brian C Coe, Jana Huang, Taneera Ghate, Anthony E Lang, Connie Marras, Douglas P Munoz

2020-Current year OA Pubs

Oculomotor behaviour changes in patients with Parkinson's disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk.Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and …

Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV), a common sexually transmitted infection in the US, contributes to oropharyngeal and urogenital cancers. To improve HPV vaccine uptake, quality improvement (QI) interventions that address barriers to vaccination in primary care may help. This study aims to understand pediatric primary care providers' (PCP) perspectives on participating in an HPV QI intervention that utilized practice facilitation to improve HPV vaccine uptake in pediatric primary care clinics.

METHODS: Participants were pediatric PCPs whose clinics completed a QI intervention that utilized practice facilitation led by an outside facilitator. One PCP from each practice completed a 15-min semi-structured exit interview. …

The Effect Of A Low-Carbohydrate Diet On Evoked Pain And Quality Of Life In Non-Hispanic Black Women With Knee Osteoarthritis: A Pilot Study, Asia M Wiggins, Larissa J Strath, Gray E Mcpherson, Barbara A Gower, Amy M Goss, Burel R Goodin, Robert E Sorge

2020-Current year OA Pubs

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent chronic pain condition that can significantly impact quality of life and contribute to recognized chronic pain racial disparities. We have shown that a low-carbohydrate diet (LCD) can reduce KOA-related pain. Our previous work suggested that the LCD was more beneficial for women and non-Hispanic Black (NHB) adults, but our sample was not sufficiently diverse. Thus, we sought to determine whether the LCD may be beneficial for NHB women with KOA on measures of self-reported and evoked pain.

METHODS: Fourteen NHB women (M = 55.93, S.D. = 7.79 years of age) with KOA were …

Il-12 Encoding Ondv Synergizes With Car-T Cells In Orthotopic Models Of Non-Small Cell Lung Cancer, Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells …

Epilepsy Therapies Symposium | Do We Really "Outgrow" Seizures?, Adam Ostendorf, Genna J Waldman, Lara Jehi, Mohammed Ilyas, Dean Naritoku, Alica M Goldman

Faculty, Staff and Students Publications

Initiation and maintenance of antiseizure therapy can be relatively straightforward in most patients. Depending on epilepsy type, patients may be more or less likely to enter remission or a resolution of their epilepsy and the International League Against Epilepsy developed clinically guiding definitions in this regard. The mechanisms by which resolution or remission are achieved are poorly understood which complicates clinical decision making and risk estimate for future seizure relapse. The impetus for the maintenance of medical therapy in a seizure-free patient is also age-dependent. In children, one ought to consider the unknown effects of antiseizure medications on the developing …

Quinoline-Based Compounds Can Inhibit Diverse Enzymes That Act On Dna, Jujun Zhou, Qin Chen, Ren Ren, Jie Yang, Bigang Liu, John R Horton, Caleb Chang, Chuxuan Li, Leora Maksoud, Yifei Yang, Dante Rotili, Abhinav K Jain, Xing Zhang, Robert M Blumenthal, Taiping Chen, Yang Gao, Sergio Valente, Antonello Mai, Xiaodong Cheng

Faculty, Staff and Students Publications

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (9) or methylpiperazine (11), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and Clostridioides difficile CamA. These compounds (9 and 11) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study …

Platelets On Fire During Chemotherapy, K Vinod Vijayan

Faculty, Staff and Students Publications

No abstract provided.

Administering Tolfenamic Acid To Gilts And Sows Before Artificial Insemination Did Not Improve Litter Size But Tended To Reduce Post-Service Serum Prostaglandin F2Α Levels, Pachara Pearodwong, Nithitad Jiebna, Padet Tummaruk

The Thai Journal of Veterinary Medicine

This study examined the impact of intramuscular administration of tolfenamic acid 10 min before artificial insemination (AI) on serum PGF2α levels and reproductive performance in gilts and sows. In Experiment I, 20 gilts were divided into two groups: control (n = 10) and treatment (n = 10). Serum samples were collected 30 min before and after insemination to measure PGF2α levels. In Experiment II, 175 gilts and sows were divided into control (25 gilts and 56 sows) and treatment (16 gilts and 78 sows) groups. In both experiments, the treatment group received an intramuscular injection of 2 mg/kg tolfenamic acid …

A Case Of Isolated Sma Dissection With Failed Initial Conservative Management, Salma Emara, Madison Kropp, Masoud Akbari, Kristin Cook

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Isolated superior mesenteric dissection (ISMAD) is an uncommon condition, often diagnosed incidentally for presentations of acute abdominal pain. Early identification and treatment are crucial as complications such as bowel ischemia or vessel rupture can occur. There remain no established treatment guidelines, making surgical and endovascular indications controversial. A 60-year-old male presented with acute abdominal pain, and was diagnosed with ISMAD via computed tomography imaging. He was initially managed conservatively which progressed to worsening abdominal pain, hypertensive crisis, and hemoperitoneum on follow-up computed tomography angiography (CTA). A mesenteric angiogram revealed a pseudoaneurysm in the superior mesenteric artery (SMA) which was subsequently …

Use Of Adventure To Address Play Deprivation In Children And Teens Raised In Conflict, Kristin Salisbury, Mary Jan Greer

Fall 2024 OTD Capstone Symposium

Youth raised in conflict often experience extrinsic and intrinsic factors that contribute to play deprivation and occupational injustice. These factors are reviewed through interviews with stakeholders and participants and observed while embedded in an adventure program for foster and adopted youth and in a refugee camp for families and children. Current literature reveals underlying factors that contribute to play deprivation for these youth, including conditions resulting from trauma and developmental delays due to the absence of play engagement. The poster reviews the programmatic components necessary for addressing these factors through whole-person play-based programming. It considers using adventure-based programming to introduce …

Tailored Activity Program For Ltc Residents With Dementia, Madison Olds, Rebecca King

Fall 2024 OTD Capstone Symposium

Nursing home residents with dementia diagnoses should have the opportunity to participate fully in community activities and receive the proper assistance and accommodations to do so. This project developed a tailored activity program to promote socialization, occupational justice, and quality of life for residents in an assistive living facility with various diagnoses. This program provides both environmental and activity adaptations to support full engagement for all participants regardless of any preexisting deficits.

Return To Driving For Clients With Tbi: A Guide For Caregivers To Navigate Emotional Barriers Experienced By Clients, Brianna Dorsey, Mary Greer

Fall 2024 OTD Capstone Symposium

The project describes the building of an online resource for caregivers to have easily accessible resources regarding information about brain injuries, emotional barriers, and return to driving programs. Each section provides further resources for caregivers and is intended to help improve their care and medical literacy.

Educating Parents To Reduce Negative Screen Time To Promote Children’S Play, Anna Groden, Cassandra Nelson

Fall 2024 OTD Capstone Symposium

This program will consist of educating caregivers and educators on the ever growing topic of screen time and how to handle it in the current digital world. As screen time and device use continues to grow, parents need the help of an occupational therapist to help promote a healthy use of screen time and to incorporate it into play. Providing caregivers and educators with evidence-based information and interventions is imperative to helping parents navigate proper technology use. An occupational therapist will have the unique ability to help promote balanced screen time use and allowing for healthy play.

An Evidence-Based Preceptor Development Program For Nurse Anesthetists, Raleigh Todd

Doctoral Projects

Abstract

Problem Statement: The success of the student registered nurse anesthetists (SRNA) is heavily influenced by experiences in the clinical setting, often encompassing a variety of preceptors throughout their respective anesthesia programs. Despite the importance of the preceptor role, many preceptors feel unprepared, and it is estimated most certified registered nurse anesthetists (CRNAs) who precept students have received no formal training in the preceptor role.

Purpose: The purpose of this project is to develop and evaluate an evidence-based preceptor education program for CRNA preceptors, utilizing evidence from literature and input from practicing nurse anesthetists. This program helps provide support by …

Patient-Reported Outcome Measures For Mohs Reconstruction: A Systematic Review, Neha Garg, Shreya Mandloi, Natalia Queenan, Jay Trivedi, Adam Mccann, Vivian Xu, Dev Amin, Howard Krein, Ryan Heffelfinger

Jefferson Hospital Staff Papers and Presentations

OBJECTIVE: Mohs micrographic surgery (MMS) and subsequent reconstructive procedures for the treatment of facial nonmelanoma skin cancers (NMSCs) significantly impact quality of life (QoL). A validated patient-reported outcome measure (PROM) for patients who undergo Mohs reconstruction is not yet established. This study aims to systematically assess the quality of existing PROMs to determine their effectiveness in capturing the challenges faced after Mohs reconstruction for facial NMSC.

DATA SOURCES: A systematic review following established Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines was performed. Medline, PubMed, Scopus, and Cochrane databases were searched using keywords relevant to MMS, NMSC, facial reconstruction, …

Transformative Training: A Pathway Program For The Critical Care And Emergency Department Novice Nurse, Kathleen Boyle, Msn, Rn, Ccctm, Linda Seliga, Msn, Rn, Cen, Tcrn, Cpen, Tehya Utah, Bsn, Rn, Ccrn

Abington Jefferson Health Posters

Background

Working in a critical care and or emergency department is very challenging and stressful. Critical care and emergency departments have the highest acuity, are fast paced, and utilize complex technologies. Novice nurses experience a lack of confidence and increased anxiety being faced with the care of a patient in this demanding setting. Since Covid we are experiencing; a nursing shortage, high turnover, expedited nursing programs with minimal clinical experience. Due to the need for nurses, novice nurses are being hired directly into the critical care settings. High stress and low confidence can affect the novice nurse's ability to provide …

Hyperglycemia Causes Differential Change In Macrophage Population In The Lacrimal Gland, Conjunctiva And Cornea, Saleh Alfuraih, Amy Tran, Lois Kim, Rais Ansari, Ajay Sharma

Pharmacy Faculty Articles and Research

Background: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. In vitro exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population. The present study was designed to examine the effect of diabetes-associated hyperglycemia on the lacrimal gland, conjunctiva and cornea macrophage population, phenotypic changes and cytokines/chemokines.

Methods: Mouse model of Streptozotocin-induced diabetes was used to induce hyperglycemia. Immunostaining for CD11b and F4/80 was performed to stain macrophages in whole mount cornea, conjunctiva and 50 µm …

Medical School Watercooler Newsletter - December 18, 2024, Lindsay Hughes

Watercooler Newsletter

This is the Wednesday, December 18, 2024 edition of the Frederick P. Whiddon College of Medicine's newsletter -- Watercooler.

Contents include:

• 3D-printed implants help customize spine surgery
• First cohort graduates from Healthcare Leadership Certificate Program
• Internal Medicine residents collect donations for Goodwill's Care Closet
• Medical student presents research on opioid education program at AAMC conference

Breast Cancer Survivorship, Jayde Mosley, Rebecca King

Fall 2024 OTD Capstone Symposium

Activities of daily living become difficult for clients during breast cancer survivorship due to the physical and emotional alterations that take place in the body. A program will provide clients with a guide on what to expect during breast cancer survivorship. This guide will also be distributed to clients who undergo mastectomy procedures and other forms of treatment. It will provide them with information regarding dos and don’ts, symptoms, long-term effects, outreach and support groups, adaptive equipment, and more information on ways to improve their quality of life.

Social Participation Approach In Brain Injury Survivors, Lexie Graham, Cassandra Nelson

Fall 2024 OTD Capstone Symposium

This program will consist of educating brain injury survivors and their peers on social participation following a brain injury. With the cognitive and physical deficits that come with brain injuries, a decrease in socialization occurs due to those barriers faced. With the lack of resources aimed towards brain injuries and social participation this program is essential to ensuring everyone has access to an education platform. Providing brain injury survivors and their peers with evidence-based information and tips for socializing is vital to helping families, friends, significant others, and peers keep strong relationships and increase their quality of life.

An Ot Web-Based Stress Management Program For Acute Care Therapists, Jessica N. Alanis, Cassandra Nelson Otd

Fall 2024 OTD Capstone Symposium

Hospital burnout has become one of the many problems among many healthcare professions. Occupational therapists and physical therapists encounter many situations that are out of their control and struggle with how to handle their emotions in a fast-paced setting. The purpose of this capstone was to educate acute care therapists on developing good stress management habits using various grounding, sensory, and mindfulness techniques to help them get through the work day. By helping acute care therapists develop good stress management habits, therapists can experience improvement in the way they carry out their duties, improve their productivity, and improve the way …

Increasing Leisure Activity Participation And The Quality Of Life Of People With Dementia And Their Caregivers, Karla Vela, Rebecca King, Keegan Mckay

Fall 2024 OTD Capstone Symposium

The problems associated with the progression of dementia, such as increased stress, and a decrease in engagement in leisure activities and social participation have a negative impact on the patients’ and caregivers’ quality of life. In addition, there is limited research on the long-term impact of occupational therapy leisure activity programs on patients with dementia and their caregivers’ quality of life. A leisure activity program was created for people with dementia and their caregivers to improve their leisure activity engagement and quality of life. Overall, the participant’s and caregivers benefitted from this program and had positive opinions based on the …